Thesis Final

A RETROSPECTIVE COMPARATIVE STUDY OF TOXICITIES AND OUTCOMES
BETWEEN GEMCITABINE + NAB PACLITAXEL AND FOLFIRINOX IN LOCALLY

`ADVANCED CA PANCREAS RECEIVING IN NEO-ADJUVANT CHEMOTHERAPY
Thesis submitted to Jawaharlal Nehru Technological University, Hyderabad in partial fulfilment of

the requirement for the award of the degree of
DOCTOR OF PHARMACY
SUBMITTED BY:
Mariam Abdul Samad 18451T0006
Maveya Afreen 18451T0009
Nazneen Kouser 18451T0010
Shaik Musaib Zubedi 18451T0030
PHARMD 5TH YEAR 2022-2023
UNDER THE GUIDANCE OF
GUIDE : CO GUIDE :
Ms. Khawaja Amtul Raouf Qazi Dr. B. Nanditha Sesikeran
M.Pharm (Pharmacology) MBBS, MD, FRCR , MRCP
ASSISTANT PROFESSOR CONSULTANT ONCOLOGIST
DEPT. OF PHARMACOLOGY (SUCP) AIG HOSPITALS GACHIBOWLI
SULTAN – UL – ULOOM COLLEGE OF PHARMACY

(Recognized by AICTE & Approved by Pharmacy Council Of India)
(Affiliated to JNTUH and B. Pharm program accredited by NBA)
Mount Pleasant, 8-2-249, Road No.3, Banjara hills, Hyderabad – 500034
TELANGANA STATE, INDIA
(O): 040-23280222
Email: suucop@yahoo.com
Website: www.sultanuloompharmacy.ac.in
SULTAN-UL-ULOOM COLLEGE OF PHARMACY

(AFFILIATED TO J.N.T.U-HYDERABAD)
(Estd. By Sultan-ul-Uloom Education Society)
Office:
“Mount Pleasant”
8-2-249, Road No 3, Banjara Hills,
Hyderabad-34, TS.
CERTIFICATE
This is to certify that the project work entitled “A RETROSPECTIVE

COMPARATIVE STUDY OF TOXICITIES AND OUTCOMES
BETWEEN GEMCITABINE + NAB PACLITAXEL AND FOLFIRINOX
IN LOCALLY `ADVANCED CA PANCREAS RECEIVING IN NEO-
ADJUVANT CHEMOTHERAPY” is a bonafide research work that has been
successfully completed by MARIAM ABDUL SAMAD (18451T0006),
MAVEYA AFREEN (18451T0009), NAZNEEN KOUSER (18451T0010),
SHAIKH MUSAIB ZUBEDI (18451T0030). The work mentioned in this
dissertation was carried out at Department of Pharmacy Practice, Sultan-ul-
Uloom College of Pharmacy and AIG Hospitals, Gachibowli under the
guidance and supervision of Ms. Khawaja Amtul Raouf Qazi M. Pharm and
Dr. Nanditha sesikeran, Consultant Oncologist, AIG Hospitals and has been
submitted during the academic year 2022-2023, for partial fulfilment of
requirements for the award of degree of Doctor of Pharmacy as per the norms
of JNTU-Hyderabad.
PRINCIPAL
Dr. ANUPAMA KONERU
M Pharm., Ph.D
(O): 040-23280222

Office:
Hyderabad-34, TS.
CERTIFICATE
This is to certify that the project work entitled “A RETROSPECTIVE

ADJUVANT CHEMOTHERAPY” is a bonafide research work that has been
successfully completed by MARIAM ABDUL SAMAD (18451T0006),
MAVEYA AFREEN (18451T0009), NAZNEEN KOUSER (18451T0010),
SHAIKH MUSAIB ZUBEDI (18451T0030). The work mentioned in this
dissertation was carried out at Department of Pharmacy Practice, Sultan-ul-
Uloom College of Pharmacy and AIG Hospitals, Gachibowli under the
guidance and supervision of Ms. Khawaja Amtul Raouf Qazi M. Pharm and Dr.
Nanditha sesikeran, Consultant Oncologist, AIG Hospitals and has been
submitted during the academic year 2022-2023, for partial fulfillment of
requirements for the award of degree of Doctor of Pharmacy as per the norms
of JNTU-HYDERABAD.
Signature of Guide Signature of External

Ms. Khawaja Amtul Raouf Qazi
Assistant professor
Department of Pharmacology
Sultan ul – uloom college of pharmacy
(O): 040-23280222

Office:
Hyderabad-34, TS.
DECLARATION
We hereby declare that the dissertation entitled “A RETROSPECTIVE
ADJUVANT CHEMOTHERAPY” DY IN EMERGENCY
DEPARTMENT IN A TERTIARY CARE HOSPITAL” is a bonafide and
genuine research work carried out under the guidance AIG Hospitals,
Gachibowli under the guidance and supervision of Ms. Khawaja Amtul Raouf
Qazi M. Pharm and Dr. Nanditha sesikeran, Consultant Oncologist, AIG
Hospitals and the work has been submitted in partial fulfillment of the
requirements for the award of Degree of Doctor of Pharmacy as per the norms
of JNTU-HYDERABAD.
MARIAM ABDUL SAMAD H.T. NO – 18451T0006

MAVEYA AFREEN H.T. NO – 18451T0009
NAZNEEN KOUSER H.T. NO – 18451T0010
MUSAIB ZUBEDI H.T. NO – 18451T0030
DATE:
PLACE: HYDERABAD
ACKNOWLEDGEMENT
We would like to express our gratitude to our principal, Dr. Anupama Koneru,
M.Pharm, Ph.D., for providing us with the opportunity to carry out this project
so efficiently and with an ease.
We sincerely thank our guide, Ms. Khawaja Amtul Raouf Qazi, for her constant
support and motivation and for sharing her valuable time in providing valuable
knowledge, guidance and excellent support for the successful completion of our
project.
We would like to express our sincere gratitude to Dr Nanditha sesikeran
(Consultant oncologist, AIG Hospitals, Gachibowli), Dr Santhosh reddy
(Clinical Pharmacist manager, AIG Hospitals, Gachibowli) for their constant
support and help throughout the project during our study in hospital and the
nurses and all the hospital staff of AIG Hospitals for all the support and co-
operation during the project work.
We would also express our thanks to all teaching faculties especially to Dr. J.
Raghuram, Dr. Mohd. Ashfaq Hussain, Dr. Syed Jaffer, Mr. Mir Mansoor Ali
for their support and suggestions all the time.
MARIAM ABDUL SAMAD

MAVEYA AFREEN
NAZNEEN KOUSER
MUSAIB ZUBEDI
TABLE OF CONTENTS
S.No CONTENT PG. NO
1. Introduction 1-19
2. Literature review 20-23
3. Aim and objective 24
4. Methodology 25-26
5. Results 27-46
6 Discussion 46-48
7. Conclusion 49
8. References 50-53
9. Annexure 54-62
DEPARTMENT OF PHARMACY PRACTICE SUCP

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ACRONYMS AND ABBREVIATIONS
S.NO Abbreviations Explanation

1. ADR Adverse drug reaction
2. BRPC Borderline resectable pancreatic
cancer
3. CT Scan Computed tomography
4. DNA Deoxyribonucleic acid
5. DPD Dihydropyridine dehydrogenase
6. ECOG Eastern cooperative oncology group
7. EUS Endoscopic ultrasound
8. Ecog Eastern cooperative oncology group
9. FFX Folfirinox
10. F - UMP 5 – fluorooxyridine monophosphate
11. FNA Fine needle aspiration
12. FOLFIRINOX Flouorouracil, leucovorin,
irinitecon, oxaliplatin
13. GnP Gemcitabine + nab – paclitaxel
14. LAPC Locally advanced pancreatic cancer
15. Pet - scan Positron emission tomography
16. RNA Ribonucleic acid
17. TNM Tumor, node & metastatis
18. wbc White blood cell

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LIST OF TABLE
S.no Title Pg no.

1. Treatment Group 27.
2. Age Distribution 28.
3. Distribution Based on Gender 30.
4. Cycle 31.
5. Laboratory Parameters 33.
6. Comparison of Adverse Events 35.
7. Delay 38.
8. Cycle Completed 39.
9. Total Cycle 41.
10. Tumor response 42.
11. Operability rate 44.
12. Mortality 45.

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LIST OF FIGURES
S.no Title Pg no.

1. Treatment Group 28.
2. Age Distribution 29.
3. Distribution Based on Gender 30.
4. Cycle 32.
5. Laboratory Parameters 34.
6. Hematological Toxicity 37.
7. GI Toxicity 37.
8. Delay 39.
9. Cycle Completed 40.
10. Total Cycle 42.
11. tumor response 43.
12. Operability rate 44.
13. Mortality 46.

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ABSTRACT
Neo adjuvant chemotherapy with Gemcitabine/nab-paclitaxel

(GEMCITABINE + NAB - PACLITAXEL) and FOLFIRINOX
(FOLFIRINOX) are two standard therapies for patients who has
locally advanced pancreatic cancer (LAPC). We retrospectively
compared the efficacy and safety of the two treatment regimens in
patients who has un-resectable pancreatic cancer. The sample size
consisted of 96 patients who has locally advanced pancreatic cancer.
(Gnp) Gemcitabine and nab – paclitaxel is Group I (N=53),
FOLFIRINOX consisting of leucovorin, fluorouracil, irinotecan and
oxaliplatin is Group II (N=43). The Primary objectives of our study
were to compare toxicities between GEMCITABINE + NAB -
PACLITAXEL and FOLFIRINOX and to evaluate the safety of
these regimens The secondary objective was % reduction of tumor ,
Surgery (% of patients who underwent surgery) and overall survival
both estimated using the independent t- test and chi-square test.
Results:. The haematological toxicities rates were similar between

the two groups (62% vs. 63%; p > 0.05), with similar anaemia
toxicities rates (62%). The neutropenia toxicity rates were similar
(15% vs 16%;p>0.05) and febrile neutropenia, thrombocytopenia,
GI toxicities were high in group II in comparison to group I.
In analysis % reduction of tumor was similar between both groups
with a P value of 0.3510 which was calculated by dependent t – test.
Patients who underwent surgery were slightly more in Group I

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A retrospective comparative study of toxicities and outcomes between gemcitabine + nab paclitaxel and
folfirinox in locally advanced ca pancreas receiving in neo-adjuvant chemotherapy
INTRODUCTION
PANCREATIC CANCER
As pancreatic cells start to proliferate and gather into a mass,
pancreatic cancer develops. These malignant cells have the capacity
to spread to other bodily parts[1]. Exocrine cells and neuroendocrine
cells, including islet cells, are two types of pancreatic cells that can
develop into pancreatic cancer. Islet cell tumours, a less frequent
type of pancreatic neuroendocrine tumour, have a better prognosis[2].
ABOUT PANCREAS
The pancreas is a retroperitoneal gland located behind the greater

curvature of the stomach, measuring 12 to 15 cm (5 to 6 inches) long
and 2.5 cm (1 inch) thick. The pancreas is made up of three parts: a
head, a body, and a tail that is usually connected to the duodenum
by two tubes. The head is an extension of the organ near the
duodenum's bend. The central body and tapering tail are located
above the head and on the left side. Exocrine cells secrete pancreatic

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Juice into small ducts, which eventually merge into two large ducts
(pancreatic and collateral ducts). These then carry secretions to the
small intestine. The pancreatic duct, also known as the duct Wirsung
(VER-sung), is the larger of the two ducts. For the pancreatic duct
merges with the common duct of the liver and merges into the
duodenum as an enlarged common duct, hepatopancreatic ampoule,
or ampulla to go into. The paternal (called PAH-ter.) ampulla opens
in a clean slice of duodenal mucosa known as the papilla major,
about 10 cm (4 inches) below the pyloric sphincter of the stomach.
The hepatopancreatic ampulla. Its passage through to the small
intestine is regulated by a mass of smooth muscle that surrounds the
hepatopancreatic ampulla, called the sphincter of Oddi (OD-8). [3]
EPIDEMOLOGY
Pancreatic cancer (PC) is a rare cancer that has the 14th highest
incidence and 7th highest mortality rate in the world. The pancreas
ranks 24th in India, with 10860 new cases (1.03%), and 18th in
mortality.[4]
The figures come from India's Population Based Cancer Registry
(PBCR). The number of cases is expected to increase from 10,969
in 2015 to 11,655 in 2020, but it is not one of India's top ten cancer
centres. Mizoram has the highest age-adjusted incidence, with
significantly more PC cases in the north eastern region than in the
rest of the country. [5]
RISK FACTORS
 Age
 Race
 Gender
 Inherited genetic syndromes(brca1, brca2, palb2, prss1)
 Family history
 Diabetes
 Smoking

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 Obesity and inactivity

 Chronic pancreatitis
 High fat diet
 Lycopene and selenium
 Chemical exposure
 Alcohol
CLINICAL PRESENTATION
Early pancreatic cancers frequently show no signs or symptoms.
When they finally manifest as symptoms, they have frequently
grown to be very large or have spread outside the pancreas.
Exhibiting one or more signs listed below does not always suggest
that you have pancreatic cancer. Many of these symptoms, in fact,
are more likely to be caused by other conditions.
 Abdominal or back pain
 Weight loss
 Poor appetite
 Nausea and vomiting
 Gallbladder or liver Enlargement
 Blood clots
 Jaundice and related symptoms
 Dark urine
 Light coloured or greasy stool
 Itchy skin
DIAGNOSIS
For most cancers, a biopsy is the only sure way for a doctor to
determine if the part of the body has cancer. Biopsy of pancreatic
cancer is notoriously difficult to perform due to the location of the
pancreas. If a biopsy is not possible, other tests to help make the
diagnosis.
 Physical examination
 Yellowish discolouration of skin eyes and tongue which
is a sign of jaundice. Jaundice can be caused by a tumour
in the head of the pancreas that prevents the normal flow

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 Of bile, a substance produced in the liver. When

pancreatic cancer is diagnosed, many people do not have
jaundice.
 ASCITES –collection of fluid in the abdomen.
 Tumour marker - Carbohydrate antigen 19-9 (CA19-9) levels
are frequently elevated in people with pancreatic cancer,
though some patients have normal CA19-9 levels. CA19-9
levels frequently rise as the cancer progresses or spreads.
 Imaging tests
 Computed tomography (CT or CAT) - Computed
tomography can be used to determine the size and
location of the primary tumour and to evaluate whether
it has spread to other parts of the body or lymph nodes.
 PET-CT scan - it is a type of positron emission
tomography (PET) scan. A PET scan is frequently
combined with a CT scan (see above), resulting in a
PET-CT scan. PET scans are used to assess the
metabolic activity of cancer cells.
 ULTRASOUND
 Transabdominal ultrasound
 Endoscopic ultrasound (EUS)
 BIOPSY
 Fine needle aspiration (FNA)
 Core needle biopsy [6]
PATHOPHYSIOLOGY
Pancreatic cancer is a disease characterized by the abnormal growth
of cells in the pancreas, which is an organ located behind the
stomach and responsible for producing enzymes that aid in digestion
and hormones that regulate blood sugar levels.
The pathophysiology of pancreatic cancer involves complex
changes at the cellular and molecular levels that result in the
development of malignant tumors.
Genetic mutations: The development of pancreatic cancer is often
associated with genetic mutations that occur in the DNA of

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pancreatic cells. Mutations in tumor suppressor genes (such as TP53,

CDKN2A, and SMAD4) and oncogenes (such as KRAS) can disrupt
the normal cell cycle and promote the uncontrolled growth and
division of cells.
Inflammation: Chronic inflammation of the pancreas (pancreatitis)
is a risk factor for pancreatic cancer. Inflammatory cells release
cytokines and growth factors that can promote the growth of cancer
cells and impair the immune system's ability to recognize and
eliminate them.
Tumor microenvironment: The tumor microenvironment in
pancreatic cancer is characterized by a dense network of blood
vessels (angiogenesis), immune cells, and other supporting cells
(such as cancer-associated fibroblasts). These cells secrete growth
factors and cytokines that promote tumor growth and survival.
The initiation and progression of pancreatic cancer can be described
as follows:
Initiation:
The initiation of pancreatic cancer is believed to occur as a result of
DNA damage in the cells of the pancreas. This damage may be
caused by various factors, including genetic mutations, exposure to
carcinogens, inflammation, and oxidative stress. The most common
genetic mutations associated with pancreatic cancer are mutations in
the KRAS, TP53, and CDKN2A genes.
Progression:
After the initiation of pancreatic cancer, the disease progresses
through several stages, characterized by the growth and spread of
cancer cells. The stages of pancreatic cancer can be described as
follows:
In situ neoplasia: In this stage, the cancer cells are confined to the
ducts of the pancreas and have not yet invaded the surrounding
tissues. This stage is also known as pancreatic intraepithelial
neoplasia (PanIN).

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Localized tumor: In this stage, the cancer cells have formed a mass
or tumor within the pancreas but have not spread to other parts of
the body. This stage is also known as stage I or II pancreatic cancer.
Locally advanced tumor: In this stage, the cancer cells have invaded
nearby tissues and organs, such as the duodenum, stomach, or bile
ducts. This stage is also known as stage III pancreatic cancer.
Metastatic cancer: In this stage, the cancer cells have spread to other
parts of the body, such as the liver, lungs, or bones. This stage is also
known as stage IV pancreatic cancer.
During the progression of pancreatic cancer, several factors
contribute to the aggressive behaviour of the cancer cells. These
factors include the production of growth factors, cytokines, and
chemokines that promote the growth and survival of cancer cells, as
well as the inhibition of the immune system's ability to recognize
and destroy cancer cells.
In summary, pancreatic cancer is a complex disease that involves the
initiation and progression of cancer cells in the pancreas.
Understanding the pathophysiology of pancreatic cancer is crucial
for developing effective prevention and treatment strategies for this
deadly disease.
STAGES OF PANCREATIC CANCER
Pancreatic cancer is classified into different stages based on the size
and extent of the tumor and whether it has spread to other parts of
the body. The most commonly used system for staging pancreatic
cancer is the TNM staging system, which stands for tumor, node,
and metastasis.
Here are the stages of pancreatic cancer according to the TNM
staging system:
 Stage 0: This is also known as carcinoma in situ, and it means
that abnormal cells have been found in the lining of the
pancreas but have not spread beyond it.

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 Stage I: The tumor is confined to the pancreas and measures

less than 2 centimetres (cm) in diameter.
 Stage II: The tumor has grown larger than 2 cm and may have
invaded nearby organs or structures, such as the duodenum,
bile ducts, or lymph nodes.
 Stage III: The tumor has spread to nearby blood vessels,
lymph nodes, or other organs, such as the spleen, stomach, or
colon.
 Stage IV: The cancer has spread to distant parts of the body,
such as the liver, lungs, or bones.
LOCALLY ADVANCED PANCREATIC CANCER

Locally advanced pancreatic cancer (LAPC) is a form of pancreatic
cancer that has spread to nearby tissues and organs but has not yet
metastasized to distant sites in the body. Gene mutations are
common in pancreatic cancer, and several genetic changes have been
identified that are associated with LAPC.
One of the most common mutations in pancreatic cancer is the
KRAS gene mutation, which is found in up to 90% of cases. KRAS
mutations are also frequently seen in LAPC. Other genetic changes
commonly found in LAPC include mutations in the TP53, SMAD4,
and CDKN2A genes.
Mutations in the TP53 gene, which is involved in cell cycle
regulation and DNA repair, are associated with poor prognosis and
resistance to chemotherapy in pancreatic cancer. SMAD4 mutations
are also associated with a poor prognosis and may contribute to the
invasiveness of pancreatic cancer cells. CDKN2A mutations, which
are involved in cell cycle regulation, are associated with a higher risk
of developing pancreatic cancer.
Identifying these gene mutations in LAPC may have implications
for treatment. For example, drugs that target KRAS mutations are
currently being developed and may provide a new avenue for
treatment. Additionally, patients with TP53 mutations may benefit
from alternative treatment strategies, such as immunotherapy or

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Targeted therapies. Overall, understanding the genetic changes that

occur in LAPC may lead to better personalized treatments and
improved outcomes for patients
TREATMENT OPTIONS OF PANCREATIC CANCER

 Surgery
 Radiation therapy
 Chemotherapy
 Targeted therapy
 Immunotherapy
Surgery
Surgery for pancreatic cancer includes removing all or part of the
pancreas, depending on the location and size of the tumor in the
pancreas. An area of healthy tissue around the tumor is also often
removed. This is called a margin. A goal of surgery is to have “clear
margins” or “negative margins,” which means that there are no
cancer cells in the edges of the healthy tissue removed.
Surgery for pancreatic cancer may be combined with systemic
therapy and/or radiation therapy.
Different types of surgery are performed depending on the purpose
of the surgery.
 Laparoscopy. Sometimes, the surgeon may choose to start with
a laparoscopy. During a laparoscopy, several small holes are
made in the abdomen and a tiny camera is passed into the body
while the patient receives anaesthesia. Anaesthesia is medication
to help block the awareness of pain. During this surgery, the
surgeon can find out if the cancer has spread to other parts of the
abdomen. If it has, surgery to remove the primary tumor in the
pancreas is generally not recommended.

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 Surgery to remove the tumor. Different types of surgery are

used depending on where the tumor is located in the pancreas. In
all of the surgeries discussed below, nearby lymph nodes are
removed as part of the operation. More than 1 type of surgeon, as
well as other specialists, will usually be involved in your surgery.
 Whipple procedure. This surgery is also referred to as a
pancreaticoduodenectomy. A Whipple procedure may be
done if the cancer is located only in the head of the pancreas.
This is an extensive surgery in which the surgeon removes the
head of the pancreas and the part of the small intestine called
the duodenum, as well as the bile duct and stomach, or
sometimes just part of the stomach. Then, the surgeon
reconnects the digestive tract and biliary s
 Distal pancreatectomy. This surgery is commonly done if

the cancer is located in the left side of the tail of the pancreas.
In this surgery, the surgeon removes the tail and body of the
pancreas, as well as the spleen.

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o Total pancreatectomy. If the cancer has spread throughout

the pancreas or is located in many areas in the pancreas, a total
pancreatectomy may be needed. A total pancreatectomy is the
removal of the entire pancreas, part of the small intestine, a
portion of the stomach, the common bile duct, the gallbladder,
and the spleen.
Supportive surgery and palliative procedures are often
recommended to help with symptoms impacting a patient’s quality
of life. Examples of palliative procedures and surgery can include
bypass surgery, stent placements, and nerve blocks to alleviate
jaundice, nausea and vomiting, and tumor-associated pain.
Side effects of surgery include weakness, tiredness, and pain for the
first few weeks after the procedure. Other side effects caused by the
removal of the pancreas sometimes include difficulty digesting food
and diabetes from the loss of insulin produced by the pancreas.
Radiation therapy
Radiation therapy is the use of high-energy x-rays or other particles
to destroy cancer cells. The most common type of radiation
treatment is called external-beam radiation therapy, which is
radiation given from a machine outside the body.
External-beam radiation therapy is the type of radiation therapy used
most often for pancreatic cancer. A radiation therapy regimen, or
schedule, usually consists of a specific number of treatments given
over a set period of time. There are different ways that radiation
therapy can be given:
 Traditional radiation therapy. This is also called
conventional or standard fraction radiation therapy. It is made
up of daily treatments of lower doses of radiation per fraction
or day. It is given over 5 to 6 weeks in total and is generally
given during the week with weekends off from treatment.

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 Stereotactic body radiation (SBRT) or cyber knife. These

are shorter treatments of higher doses of radiation therapy
given over as few as 5 days. This is a newer type of radiation
therapy that can provide more localized treatment in fewer
treatment sessions. Whether this approach works as well as
traditional radiation therapy is not yet known, and it may not
be appropriate for every person. It should only be given in
specialized centres that have experience and expertise in using
this technology for pancreatic cancer and identifying who it
will work best for.
 Proton beam therapy. This is a type of external-beam
radiation therapy that uses protons rather than x-rays. At high
energy, protons can destroy cancer cells. This type of therapy
also lessens the amount of healthy tissue that receives
radiation. Proton beam therapy may be given for a standard
amount of time or for a shorter time like SBRT.
NEOADJUVANT CHEMOTHERAPY OF LOCALLY

ADVANCED PANCREATIC CANER
Curative resection of pancreatic cancer occurs in just 10% to 15% of
patients, and surgical resection is now the only method for the
radical therapy of pancreatic cancer.[7]
Therefore, it is crucial for the treatment of pancreatic cancer to figure
out how to make cases that are un-resectable into ones that can be.
Locally advanced pancreatic cancer (LAPC), in which an upfront
resection is thought to be harmful because of the disease's substantial
vascular involvement and high risk of a non-radical resection.[8]
Neo-adjuvant chemotherapy (NCT) is an efficient method that
enables the radical excision of locally advanced and borderline
resectable pancreatic cancer (BRPC) (LAPC)

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The neo-adjuvant chemotherapy for locally advanced pancreatic

cancer consists of the following anti-cancer medications:-
 fluorouracil (5-FU)
 gemcitabine
 irinotecan
 leucovorin
 Nab-paclitaxel.
 irinotecan
 Oxaliplatin.
As first – line treatment of locally advanced pancreatic cancer
Clinical practise guidelines recommend two multi-drug regimens for
patients:
 Gemcitabine plus nab-paclitaxel (GnP) and
 FOLFIRINOX (oxaliplatin, irinotecan, fluorouracil, and
leucovorin).[9,10,11,12]
 Gemcitabine plus nab- paclitaxel ( GnP)

Gemcitabine and a nanoparticle albumin-bound version of paclitaxel
make up the combination medication ( GnP).
 Treatment guidelines:_
Gemcitabine and nab-Paclitaxel chemotherapy is administered in a
cycle of three portions, each given seven days apart.
 Medications before chemotherapy ( prechemo – meds).
• Pre chemo medications are used to combat the typical side
effects of chemotherapy that are predicted to occur.
• It can be anti-emetic, anti-allergic and anti-diarrheal.
• Antiemetic agents which are commonly used are,
corticosteroids,5-ht3antagonists (ondansetron, palonosetron),
and NK1 antagonists (aprepitant, fosaprepitant).

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 Drug information
1) Gemcitabine
Dose: - 1000-1600 mg/m2
PHARMACOLOGY PHARMACOKINETICS
Mechanism of action is a 1. Distribution. Plasma protein binding
nucleoside analogue of of gemcitabine is negligible.
deoxycytidine. A pyrimidine 2. Metabolism: Gemcitabine is
analogue that inhibits both metabolized in the liver
DNA and RNA viruses, this 3. Elimination: 99% of the drug and its
antimetabolite blocks cells metabolic substances are excrete
through the cell cycle in G1/S through urine and almost 1% of the
dose was excreted in the stools.
ADVERSE EFFECTS
• stomatitis
• flu-like symptoms
• constipation
• nausea
• edema.
• Vomiting
• hearing loss,
• rash
• alopecia,
• sensory neuropathy
• infection
• anaemia,
• leukopenia,
• neutropenia,
• thrombocytopenia,
• muscle weakness,
• haematuria,

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• paraesthesia,
• fatigue,
• somnolence,
• peripheral
• diarrhoea
• dyspnea
Pregnancy (teratogenic category): Category D.
2) nab-Paclitaxel
Dose: - 125-200 mg/m2
MOA: it is an anti-microtubule Absorption: NA
agent that prevents Distribution: 94% of Nab-
Depolymerisation. paclitaxel is bond to plasma
proteins.
Metabolism: Nab-paclitaxel is
extensively metabolized
by hepatic CYP2C8 enzymes.
Excretion: only 4% of nab-
paclitaxel is excreted through
urine and around 20 % is found
in stools.
ADVERSE EFFECTS.
• Asthenia
• Neutropenia
• Febrile neutropenia
• Mucositis
• Thrombocytopenia
• Anaemia
• Hypersensitivity Reactions (HSRs)
• Vomiting
• Arthralgia / Myalgia
• Nausea
• Diarrhoea
Pregnancy (teratogenic category): category D

14
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Drug Interactions: Paclitaxel metabolism may be affected by

cytochrome P450 (CYP) agonists that inhibit these enzymes.
 FOLFIRINOX (oxaliplatin, irinotecan, fluorouracil, and
leucovorin).
Fluorouracil, leucovorin, irinotecan and oxaliplatin make up
the combination medication Folfirinox (FFX)
 Treatment guidelines
Each chemotherapy cycle of FOLFIRINOX is administered
on days 1 ad 15 every 4 weeks.
• Medications before chemotherapy ( prechemo – meds).
• Pre chemo medications are used to combat the typical side
effects of chemotherapy that are predicted to occur.
• It can be anti-allergic, anti-emetic, and anti-diarrheal. •
Appropriate antiemetic agents include, but are not limited to,
corticosteroids, 5-HT3 antagonists (ondansetron,
palonosetron), and NK1 antagonists (aprepitant,
fosaprepitant).
 Drug information
1) Fluorouracil (5fu)
DOSE - 5-fluorouracil (5-FU) (bolus (0-400 mg/m2) +
intravenous infusion (2400 – 3600 mg/m2)
Moa: Fluorouracil which Absorption: When fluorouracil
is an anti-metabolite of is administered intravenously
pyrimidine analogues. It quickly, its initial levels in the
disrupts DNA synthesis blood and bone marrow surge
and RNA in the S phase and then sharply decline.
of cell division. Fluorouracil levels remain
steady in the plasma after a
protracted infusion, but they
drastically decrease in the bone
marrow.
The blood-brain barrier is easily
crossed by this substance, which
then diffuses easily into the

15
(J.N.T.U.H)
cerebrospinal fluid and brain

tissue.
Dihydropyridine dehydrogenase
(DPD) is largely responsible for
its metabolism in the liver, where
it produces the active
metabolites 5-fluorooxyuridine
monophosphate (F-UMP) and 5-
5-fluoro-2'-deoxyuridine-5'- (F-
dUMP).
Excretion: The plasma half-life
of fluorouracil, which varies
depending on dose, is around 16
minutes on average. Fluorouracil
is eliminated unaltered in the
urine in amounts ranging from 7
to 20%.
ADVERSE EFFECTS
• headache
• alopecia,
• indigestion,
• hand-foot syndrome,
• vomiting,
• stomatitis,
• maculopapular rash,
• photosensitivity,
• anorexia,
• pruritis,
• esophagopharyngitis,
• diarrhoea,
• nausea,
Pregnancy (Teratogenic category): Pregnancy category D.
Drug Interactions: Fluorouracil is a potent inhibitor of CYP2C9.

16
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2) Irinotecan
DOSE : 150-180 mg/m2
Pharmacology Pharmacokinetics
Mechanism of Action: Irinotecan and 1. Absorption: No data available
SN-38, which is its metabolic are 2.Distribution: 30-70%,Protein binding
inhibiters of topoisomerase I. By occurs for irinotecan is whereas SN-38
reducing torsional stress in the DNA shows maximum protein binding of
helix during replication and RNA 95%.
transcription, topoisomerase I causes 3. Metabolism: Irinotecan is
metabolized in the liver
single-strand breaks. Irinotecan or SN-
4. Excretion: Urinary excretion of
38 stops the deregulation of single-
irinotecan is Approximately 15 to 35%.
strand breaks by attaching to the bile excretion happens for about 20%
topoisomerase I-DNA complex. When
the DNA replication fork runs into
irinotecan or the SN-38/topoisomerase I
complex, irreparable DNA damage
results in DNA double strand breaks.
ADVERSE EFFECTS
• dizziness,
• cough,
• dyspnoea,
• mucositis,
• vomiting,
• neutropenia ,
• asthenia
• rash,
• thrombocytopenia
• cholinergic reactions
• anorexia,
• constipation,
• nausea,

17
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• diarrhoea
• infection,
• leukopenia,
• alopecia,
• body weight gain.
• Pain,
Pregnancy (Teratogenic category): category D.
3. DRUG INTERACTIONS:. inhibitors or Inducers or CYP3A4,
CYP2B6, OATP1B1/SCLO1B1, P-/ABCB1 glycoproteins and
UGT1A1 may affect irinotecan blood plasma serum concentrations.
3) OXALIPLATIN
DOSE: 85 - 120 mg/m2
MOA: Oxaliplatin is an Absorption: No data available
alkylating anti cancer agent that Distribution: 20% of oxaliplatin is
prevents DNA synthesis through present in the systemic circulation.
the crosslinking of DNA The remaining 85% are rapidly
nucleotides (GNG). These cross- distributed or eliminated from the
links inhibit DNA replication cell tissue.
and transcription. Metabolism: Oxaliplatin undergoes
nonenzymatic biotransformation.
Elimination: oxaliplatin is
elimination through renal excretion.
urinary excretion is significant for
about 54% of the oxaliplatin, with
stool excretion accounting for only
about 3%.
c. ADVERSE EFFECTS
• cough
• anemia,
• diarrhea,

18
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• fever,
• nausea,
• leukopenia,
• vomiting,
• constipation
• neuropathy, ,
• loss of appetite,
• fatigue,
• thrombocytopenia,
• paresthesia,
• neutropenia,
• pain,
Pregnancy (Teratogenic category): Pregnancy category D.

19
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REVIEW OF LITERATURE
1) In a study “Gemcitabine/nab-Paclitaxel versus FOLFIRINOX for

palliative first-line treatment of advanced pancreatic cancer: A
propensity score analysis” conducted by Jakob M. Riedl,Florian
Posch,Lena Horvath published on May 02,2021 states that this
real-world comparative effectiveness study indicates that
FOLFIRINOX and GN have similar effectiveness in the
palliative first-line treatment of a PDAC.[13]
2) In the study “Current Standards of Chemotherapy for Pancreatic

Cancer” conducted by May Tun Saung, Lei Zheng, published
onSeptember,19,2017 states that Although combination
chemotherapy regimens are shown to be superior to gemcitabine
monotherapy for both metastatic pancreatic cancer and adjuvant
chemotherapy after surgical resection, it should be recognized
that all combination chemotherapy regimens offer only limited
benefits. In addition, there is a paucity of clinical trials that
directly compare the various combination chemotherapy
regimens.[14]
3) In the study “FOLFIRINOX versus Gemcitabine for Metastatic

Pancreatic Cancer” conducted by Thierry Conroy,
M.D.,Françoise Desseigne, M.D., Marc Ychou, M.D.,
Ph.D., Olivier Bouché, M.D., Ph.D., Published on May 12, 2011
states that As compared with gemcitabine, FOLFIRINOX was
associated with a survival advantage and had increased toxicity.
FOLFIRINOX is an option for the treatment of patients with
metastatic pancreatic cancer and good performance status. [15]

20
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4) In the study “Increased Survival in Pancreatic Cancer with nab-

Paclitaxel plus Gemcitabine “ conducted by Daniel D. Von Hoff,
M.D., Thomas Ervin, M.D., Francis P. Arena, M.D., E. Gabriela
Chiorean, M.D., published on October 31, 2013 states that In
patients with metastatic pancreatic adenocarcinoma, nab-
paclitaxel plus gemcitabine significantly improved overall
survival, progression-free survival, and response rate, but rates of
peripheral neuropathy and myelosuppression were increased. [16]
5) In the study ‘Consensus report of the national cancer institute

clinical trials planning meeting on pancreas cancer treatment”
conducted by Philip A Philip et al. J Clin Oncol. 2009. States that
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading
cause of cancer mortality, despite significant improvements in
diagnostic imaging and operative mortality rates. The 5-year
survival rate remains less than 5% because of microscopic or
gross metastatic disease at time of diagnosis. The Clinical Trials
Planning Meeting in pancreatic cancer was convened by the
National Cancer Institute’s Gastrointestinal Cancer Steering
Committee to discuss the integration of basic and clinical
knowledge in the design of clinical trials in PDAC. Major
emphasis was placed on the enhancement of research to identify
and validate the relevant targets and molecular pathways in
PDAC, cancer stem cells, and the microenvironment. Emphasis
was also placed on developing rational combinations of targeted
agents and the development of predictive biomarkers to assist
selection of patient subsets. The development of preclinical
tumor models that are better predictive of human PDAC must be
supported with wider availability to the research community.
Phase III clinical trials should be implemented only if there is a
meaningful clinical signal of efficacy and safety in the phase II
setting. The emphasis must therefore be on performing well-
designed phase II studies with uniform sets of basic entry and
evaluation criteria with survival as a primary endpoint. Patients
with either metastatic or locally advanced PDAC must be studied
separately.[17]

21
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6) In the study “Increased Survival in Pancreatic Cancer with nab-

Paclitaxel plus Gemcitabine” conducted by Daniel D. Von Hoff,
M.D., Thomas Ervin, M.D., published on October 31, 2013 states
that In patients with metastatic pancreatic adenocarcinoma, nab-
paclitaxel plus gemcitabine significantly improved overall
survival, progression-free survival, and response rate, but rates of
peripheral neuropathy and myelosuppression were increased. [18]
7) In the study “FOLFIRINOX for locally advanced pancreatic

cancer: a systematic review and patient-level meta-analysis”
conducted by Mustafa Suker et al. Lancet Oncol. 2016 Jun.
States that Patients with locally advanced pancreatic cancer
treated with FOLFIRINOX had a median overall survival of 24·2
months-longer than that reported with gemcitabine (6-13
months). Future research should assess these promising results in
a randomised controlled trial, and should establish which patients
might benefit from radiotherapy or chemoradiotherapy or
resection after FOLFIRINOX.[19]
8) In the study “FOLFIRINOX-based neoadjuvant therapy in

borderline resectable or unresectable pancreatic cancer: a meta-
analytical review of published studies” conducted by Fausto
Petrelli et al. Pancreas. 2015 May.states that : This meta-analysis
shows that down-staging after neoadjuvant FOLFIRINOX-based
therapy is noticeable in patients with borderline
resectable/unresectable PC, with a total R0 resection rate of
40%.[20]

22
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9) In the study”Pancreatic cancer: French clinical practice

guidelines for diagnosis, treatment and follow-up (SNFGE,
FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO,
ACHBT, AFC)” conducted by Cindy Neuzillet et al. Dig Liver
Dis. 2018 Dec. States that : Guidelines for management of PA
are continuously evolving and need to be regularly updated. This
constant progress is made possible through clinical and
translational research. However, as each individual case is
particular, they cannot substitute to multidisciplinary tumor
board discussion.[21].

23
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AIM AND OBJECTIVE

AIM:
To assess and compare the toxicities and efficacy of Gemcitabine +
nab paclitaxel and Folfirinox in patients who has locally advanced
Pancreatic Adenocarcinoma
OBJECTIVES:
1- To determine the hematological toxicities and GI toxicities of
Gemcitabine + nab – paclitaxel and Folfirinox
2- To evaluate the individual efficacies of the drug regimen

24
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METHODOLOGY
STUDY SITE:
AIG Hospitals, Gachibowli, Hyderabad
DESIGN AND DURATION OF THE STUDY
A Retrospective observational study conducted for 6 months.
SAMPLE SIZE CALCULATION:
Sample size: 100 An thorough subject selection literature review has
been carried to assess and compare the toxicities and efficacy of
Gemcitabine + nab paclitaxel and Folfirinox in patients who has
locally advanced Pancreatic Adenocarcinoma - an observational
study and based upon the literature collected from peer reviewed
articles and prevalence of the disease a sample size of 100 is
considered suitable for this research study
STUDY POPULATION:
The patients who are diagnose with locally advanced CA Pancreas
receiving in neo-adjuvant chemotherapy either Gemcitabine + nab
paclitaxel or Folfirinox will be considered.
SELECTION CRITERIA:
 INCLUSION CRITERIA:
1. Patients who has locally advanced Pancreatic Adenocarcinoma
paclitaxel or Folfirinox
2. Age group of 18-80 years.
 EXCLUSION CRITERIA:
1. Pregnancy and nursing women.
2. Patients aged less than 18 years.

25
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STUDY METHOD / STUDY PROCEDURE / METHODS OF

ASSESSMENT
The patients meeting the inclusion criteria were recruited in
Retrospective comparative study of toxicities and outcomes between
Gemcitabine + nab Paclitaxel and Folfirinox in locally advanced CA
Pancreas receiving in neo-adjuvant chemotherapy will be conducted
in Oncology department of AIG hospitals for a duration of6 months.
The data is collected from patient casefiles, medical records of
patients. The parameters used for toxicities of the drug are
haematological toxicity and GI toxicity The obtained data will be
analysed using dependent t- test.
 STUDY MEDICATIONS
1- Modified FOLFIRINOX (5-fluorouracil, irinotecan, oxaliplatin)
2- Gemcitabine with nab-Paclitaxel
 SUBJECT SELECTION
The patients who are diagnose with locally advanced CA Pancreas
paclitaxel or Folfirinox will be considered
EXPECTED OUTCOMES
Evaluation of toxicities and outcomes between FOLFIRINOX and
Gemcitabine + nab – paclitaxel
STATISTICAL ANALYSIS:
The obtained data will be entered into MS EXCEL 2010.
Quantitative variables will be summarized using descriptive studies
(percentages, mean, standard deviation, number of observations).
The data will be statistically analysed using SPSS Version. 20
software and differences between two variables will be calculated
Paired – t – test and will be represented as graphs, pie diagrams and
bar graphs.

26
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RESULTS
1- Treatment Group
The number of patients who were receiving Gemcitabine+Nab-

paclitaxel or FOLFIRINOX in neoadjuvant chemotherapy for
locally advanced pancreatic adeno carcinoma were considered
for the study.
Table 1 - Treatment Group
Group Treatment N %
I Gemcitabine + Nab paclitaxel 53 55
II FOLFIRINOX 43 45
The value in above table where calculated by chi square test to

analysis the results for Patients who were receiving
Gemcitabine+Nab-paclitaxel or FOLFIRINOX in neoadjuvant
chemotherapy for locally advanced pancreatic adeno carcinoma
were considered for the study Our calculations show that out of a
total of 96 patients 55% were receiving gem+nab paclitaxel (N=53)
and 45% patients were receiving FOLFIRINOX 9N=43).

27
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Figure 1: Treatment Group
60
Frequency 40
20
0
I II
Group
2- Age Distribution
The P-value in the Below table were calculated by independent t-

test to analyze the result for comparison of Age Distribution in
both groups.
Compared with the patients who received Gemcitabine +nab

paclitaxel those treated with FOLFIRINOX were younger.
Table 2: Age Distribution
Group Age (years) P value

Minimum Maximum Mean± SD Median
I 33 77 63.04±10.45 64
<0.0001
II 33 63 51.70±7.99 54

28
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The P-value in the above table were calculated by dependent t- test

to analyze the result for comparison of Age Distribution in both
groups.
Mean± SD of 63.04±10.45 with a minimum age of 33 and a
maximum age of 77 years has been analysed for the patients of
Group I (N=53)
Mean± SD of 51.70±7.99 with a minimum age of 33 and a
maximum of 63 years has been analysed for the patients of Group II
(N=43)
Figure 2: Age Distribution
100
80
Age (years)
60
40
20
0
I II
Group
3- Distribution Based on Gender

Male patients are significantly higher in FOLFIRINOX
regimen than in Gemcitabine+ Nab – paclitaxel group.

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Table 3 : Distribution Based on Gender
Gender Group I Group P value

(n=53) II
(n=43)
Male 26(49) 40(93)
<0.0001
Female 27(51) 03(07)
Male and Female patients were considered for the study, and it has
been calculated out of 53 patients in Group I 49% were male(N=26)
and 51% were female (N=27) and in Group II out of 43 patients 93%
were male (N=40) 75 were female (N=3).
Figure 3: Distribution Based on Gender
Group I
Group II
50
40
Frequency
30
20
10
0
MaleFemale MaleFemale
Gender

30
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4 – CYCLE
Chemotherapy cycle of Nab-paclitaxel followed by gemcitabine was
administered intravenously on days 1, 8 and 15 every 4 weeks.
Patients treated with FOLFIRINOX received chemotherapy on days
1 & 15 every 4 weeks.
No. of cycles for each Group varied according to clinicians.
Table 4: Cycle
Cycle Group I Group P

(n=53) II value
(n=43)
1 29(55) 10(23)
2 9(17) 12(28)
0.0182
3 12(22) 12(28)
4 2(04) 07(16)
5 1(02) 02(05)
For the patients in Group I (receiving neoadjuvant

gem+nabpaclitaxel therapy) out of 53 patients the results were
1%(N=1) patients received 5 cycles of chemotherapy, 4% (N=2)
patients received 4 cycles, 22% (N=12) patients received 3 cycles of
chemotherapy, 17% (N=9) patients received 2 cycles of
chemotherapy
For the patients in Group II (receiving neoadjuvant FOLFIRINOX
therapy) out of 43 patients the results were 5%(N=2) patients
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received 5 cycles of chemotherapy, 16% (N=7) patients received 4

cycles, 28% (N=12) patients received 3 cycles of chemotherapy,
28% (N=12) patients received 2 cycles of chemotherapy, 23%
(N=10) patients received 1 cycles of chemotherapy
Figure 4: Cycle
Group I
Group II
40
30
Frequency
20
10
0
1 2 3 4 10
Cycle
5 – Laboratory Parameters
To compare the toxicities between 2 groups lab parameters like Hb
count, Neutrophils, Lymphocytes and Platelet count were
considered. The p value in the above table were calculated by Chi-
square and the above graph illustrates the comparison of laboratory
parameters post initiation of neoadjuvant chemotherapy.

32
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Table 5: Laboratory Parameters

Parameter Group I Group P value
(n=53) II
(n=43)
Hemoglobin
Normal 17(32) 16(37)
0.5984
Abnormal 36(68) 27(63)
WBC
Normal 40(75) 35(81)
0.4851
Abnormal 13(25) 08(19)
Neutrophil
Normal 40(75) 35(81)
0.4851
Abnormal 13(25) 08(19)
Lymphocytes
Normal 41(77) 40(93)
0.0355*
Abnormal 12(23) 03(07)
Platelet count
Normal 42(79) 39(91)
0.1243
Abnormal 11(21) 04(09)
The p value in the above table were calculated by Chi-square and the
above graph illustrates the comparison of laboratory parameters post
initiation of neoadjuvant chemotherapy
Out of a total of 96 patients for the patients in Group I out of 53

patients the results of hemoglobin post chemotherapy were
32%(N=17) patients had normal values 68%(N=36) patients had
abnormal values, patients in Group II out of 43 patients the results
were 37%(N=16) patients had normal values 63%(N=27) patients
had abnormal values with a P value of (0.5984).
patients the results of WBC post chemotherapy were 75%(N=40)
patients had normal values 25%(N=13) patients had abnormal

33
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values, patients in Group II out of 43 patients the results were

abnormal values with a P value of (0.4851).
patients the results of Neutrophil post chemotherapy were
patients the results of Lymphocytes post chemotherapy were
patients the results of platelet count post chemotherapy were
were 91%(N=39) patients had normal values 09%(N=4) patients had
abnormal values with a P value of (0.1243
Figure 5: Laboratory Parameters
Group I
Group II
40
30
Frequency
20
10
0
s
n
nt
l
C
hi
te
bi
ou
op
y
W
lo
oc
tc
og
tr
eu
ph
le
em
te
N
la
H
Ly
Abnormal Parameters

34
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6 – Comparison of Adverse Events

The p value in the below table were calculated by Chi-square and
the above graph illustrates the comparison of Adverse events post
initiation of neoadjuvant chemotherapy.
Table 6: Comparison of Adverse Events
Adverse Event Group I Group P value

(n=53) II
(n=43)
Hematological 33(62) 27(63) 0.9577
toxicity 33(62) 27(63) 0.9577
Anemia 08(15) 07(16) 0.8737
Neutropenia 06(11) 0 0.0227*
Lymphopenia 04(08) 05(12) 0.4952
Febrile neutropenia 03(06) 03(07) 0.7910
Thrombocytopenia
GI toxicity 01(02) 02(05) 0.4389
Diarrhoea 01(02) 02(05) 0.4389
Out of a total of 96 patients for the patients in group I (N=53)

patients the results of Hematological toxicity post chemotherapy
were 62%(N=33), patients in group II (N=43) patients the results
were 63%(N=27) with a P value of (0.9577). Statistically significant
difference does not exist as P>0.05.

35
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patients the results of Anemia toxicity post chemotherapy were
62%(N=33), patients in Group II out of 43 patients the results were
63%(N=27) with a P value of (0.9577). Statistically significant
patients the results of Neutropenia toxicity post chemotherapy were
patients the results of lymphopenia toxicity post chemotherapy were
difference does exist as P<0.05.
patients the results of Febrile neutropenia toxicity post
chemotherapy were 08%(N=04), patients in Group II out of 43
patients the results were 12%(N=05) with a P value of (0.4952).
Statistically significant difference does not exist as P>0.05.
patients the results of Thrombocytopenia toxicity post chemotherapy
were 06%(N=03), patients in Group II out of 43 patients the results
were 07%(N=03) with a P value of (0.7910). Statistically significant
patients the results of GI toxicity and diarrhea post chemotherapy
were 02%(N=1) , 02% (N=1) patients in Group II out of 43 patients
the results were 05%(N=02) ,05%(N=02) with a P value of (0.4389)
for GI toxicity, (0.4389) for diarrhea. Statistically significant

36
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Figure 6: Hematological Toxicity
Group I
Group II
Thrombocytopenia
Hematological toxicity
Febrile
Lymphopenia
Neutropenia
Anemia
0 10 20 30 40
Frequency
Figure 7: GI Toxicity
Group I
2.5 Group II
2.0
Frequency
1.5
1.0
0.5
0.0
Diarrhoea
GI Toxicity

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7 – DELAY
The above graph illustrates the comparison of Delay of
chemotherapy post initiation of neoadjuvant chemotherapy.
Table 7: Delay
Delay Group I Group P
(n=53) II value
(n=43)
Yes 07(13) 02(05)
0.1526
No 46(87) 41(95)
above graph illustrates the comparison of Delay of chemotherapy
post initiation of neoadjuvant chemotherapy
For the patients in Group I (N=53) 13%(N=07) did not had any delay
in chemotherapy cycle, 87%(N=46) had delay in chemotherapy
treatment.
For the patients in Group II (N=43) 05%(N=02) did not had any
delay in chemotherapy cycle, 95%(N=41) had delay in
chemotherapy treatment.

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Figure 8: Delay
Group I
Group II
50
40
Frequency
30
20
10
0
Yes No
Delay
8 – CYCLE COMPLETED
above graph illustrates the comparison of completion of
chemotherapy cycle.
Table 8: Cycle Completed
Completed Group I Group P

(n=53) II value
(n=43)
Yes 41(77) 34(79)
0.8402
No 12(23) 09(21)

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For the patients in Group I (N=53) 77%(N=41) completed their

chemotherapy cycle, 23%(N=12) did not completed their
chemotherapy cycle.
For the patients in Group II (N=43) 79%(N=34) completed their

chemotherapy cycle, 21%(N=09) did not completed their
chemotherapy cycle. with a P value of (0.8402),
Figure 9: Cycle Completed
Group I
Group II
50
40
Frequency
30
20
10
0
Yes No
Cycle completed
9 – TOTAL CYCLE
Evaluating the number of cycles completed by the patients of both

groups will indirectly indicate the toxicity pattern of the regimen.

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Table 9: Total Cycle
Total Cycle Group I Group II
N % N %
2 10 19 05 12
3 12 23 06 14
4 14 26 16 37
5 04 8 05 12
6 13 24 11 25
For the patients in Group I(receiving neoadjuvant

gem+nabpaclitevel therapy) out of 53 patients the results were
24%(N=13) patients received 6 cycles of chemotherapy, 8% (N=04)
patients received 5 cycles, 26% (N=14) patients received 4 cycles of
chemotherapy
For the patients in Group II(receiving neoadjuvant FOLFIRINOX
therapy) out of 43 patients the results were 25%(N=11) patients
received 6 cycles of chemotherapy, 12% (N=05) patients received 5
cycles, 37% (N=16) patients received 4 cycles of chemotherapy,
14% (N=06) patients received 3 cycles of chemotherapy, 12%
(N=10) patients received 1 cycles of chemotherapy

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Figure 10: Total Cycle
10 – TUMOR RESPONSE
By calculating the percentage reduction of tumor, we can determine
whether the chemotherapy is effective and choose the best regimen.
There is no significant difference, but the percentage of tumor
reduction in group 2 is slightly higher than in group 1
Table 10: tumor response
Group Reduction P
value
Minimum Maximum Mean± SD Median
I 0 45 11.18±2.06 0
0.3510
II 0 54 8.37±2.13 0

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The P-value in the above table were calculated by dependent t- test

to analyze the result for comparison of reduction of the size of tumor
after neo – adjuvant chemotherapy in both groups.
Mean± SD of 11.18±2.06 with a minimum of 0% and a maximum
of 45% statistical reduction of tumour has been analysed for the
patients of Group I (N=53)
Mean± SD of 8.37±2.13with a minimum of 0% and a maximum of
54% statistical reduction of tumour has been analysed for the
patients of Group II (N=43)
Figure 11: tumor response
60
% reduction
40
20
0
I II
Group

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11- OPERABILITY RATE

Cancer can only be cured through surgical resection. Locally
advanced pancreatic cancer (LAPC), as we all know, is
un-resectable due to vascular involvement. The conversion of
un-resectable cancer to resectable cancer following neoadjuvant
chemotherapy is an important parameter for assessing the
regimen's efficacy.
Patients who underwent surgery following neoadjuvant
chemotherapy were slightly more numerous in group II.
Table 11: Operability rate
Surgery Group I Group

II
N % N %
Yes 10 19 11 26
No 43 81 32 74
Figure 12: Operability rate
Group I
Group II
50
40
Frequency
30
20
10
0
Yes No
Surgery

44
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The above graph represents the percentage of patients in each

respective group which underwent surgery post completion of neo-
adjuvant chemotherapy
Out of a total of 96 patients for the patients in Group I (N=53) the

results were 19% (N=10) underwent surgery and 81% (N=43) did
not underwent surgery, for the patients in Group II (N=43) the results
were 26% (N=11) underwent surgery and 81% (N=32) did not
underwent surgery.
13 - Overall survival
The p value in the below table were calculated by Chi-square and it
illustrates the comparison of Survival after treatment in both Groups.
Table 12: Mortality
Survival Group I Group P

(n=53) II value
(n=43)
Alive 36(68) 30(70)
0.8464
Dead 17(32) 13(30)

45
(J.N.T.U.H)
Figure 13: Mortality
Group I
Group II
40
30
Frequency
20
10
0
Alive Dead
Survival
The p value in the above graph were calculated by Chi-square

and the above graph illustrates the comparison of Survival after
treatment in both Groups .
For the patients in Group I (N=53) 68%(N=36) are Alive,

32%(N=17) are Dead.
For the patients in Group II (N=43) 70%(N=30) are Alive,

30%(N=13) are Dead.

46
(J.N.T.U.H)
DISCUSSION
Considering the speedy development and lethal function of

pancreatic cancer, it's far excessively essential for patients who has
to pick out their first neoadjuvant therapy strategy.
Folfirinox and Gemcitabine + nab – Paclitaxel (GnP) had been
proven to be more effective chemotherapeutic alternatives as
neoadjuvant chemotherapy in patients who has locally advanced
pancreatic cancer (LAPC) by analysing many studies [22,23].
Although neoadjuvant remedy has been widely endorsed via many
hints, together with NCCN recommendations for LAPC, the most
reliable therapeutic routine remains controversial.
Folfirinox and GNP are the maximum frequently endorsed NAC
strategies for LAPC. The standard in resectable disease is a surgical
procedure with macroscopic complete resection accompanied by
widespread adjuvant chemotherapy. For LAPC, R0 resection is the
ultimate desire that majorly decides lengthy-time period survival.
According to our retrospective study, neo-adjuvant chemotherapy
with Folfirinox slightly improves surgical outcomes and results in a
high % tumour reduction. In preceding research, Folfirinox is simply
suitable for sufferers with first-rate performance popularity without
applicable comorbidities. Almost all the medical trials had a high
chance of bias, for instance, patients of the Folfirinox group were
with more youthful age and lower ECOG degree in comparison with
GnP group, which might impair the validity of the located results.
As we mentioned before, Folfirinox had higher resection numbers
and better % reduction of tumour compared with GnP, which isn't
constant with consequences of chemotherapy response.

47
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In this study, we also compared the toxicities of two common

chemotherapy regimens. GnP was, however, generally reserved for
older and more vulnerable patients because patient groups were
uneven in terms of age. Also in our study, we discovered that
patients in the GnP group were older than those in the FFX group
and that FFX treatment was most effective in male patients.
When deciding between these two chemotherapy regimens, the
safety profile and quality of life should be taken into account.
By its toxicity or results, a drug regimen's safety may be determined.
In our retrospective comparative analysis, we discovered that the
two regimens had comparable rates of high-grade hematological
damage.
Major difference: FFX group had higher febrile neutropenia than
GnP group.

48
(J.N.T.U.H)
CONCLUSION
To provide better patient care, it is essential to compare the toxicities

and effectiveness of Gemcitabine + nab-paclitaxel and
FOLFIRINOX as neoadjuvant chemotherapy for LAPC.
Our retrospective comparative study indicates that FOLFIRINOX is
mostly preferable for young male patients, while Gemcitabine +
nab-paclitaxel is preferable for older male and female patients.
We analyzed the two regimens and found that they had similar
toxicities in terms of hematological and gastrointestinal effects.
However, our study showed that the FOLFIRINOX group had a
higher incidence of febrile neutropenia than the Gemcitabine + nab-
paclitaxel group.
Therefore, we conclude that both regimens have similar toxicities
and effects as neoadjuvant chemotherapy for LAPC patients, but the
choice between them should be based on factors such as age, gender,
and ECOG score.

49
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Martijn R. Meijerink,6 Geertjan van Tienhoven,7 Thilo
Hackert,8 Christopher L. Wolfgang,9 Hjalmar van
Santvoort,10 Bas Groot Koerkamp,11 Olivier R. Busch,1 I.
Quintus Molenaar,2 Casper H. van Eijck,11 Marc G.
Besselink,1,* and the Dutch Pancreatic Cancer Group and
International Collaborative Group on Locally Advanced
Pancreatic Cancer

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7. Locally Advanced Pancreatic Cancer: Work-Up, Staging, and

Local Intervention Strategies
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Conroy T., Louvet C., Hammel P., Mitry E., Ducreux M.,
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R., Bécouarn Y., Adenis A., Raoul J.-L., Gourgou-Bourgade
S., de la Fouchardière C., et al. FOLFIRINOX versus
Gemcitabine for Metastatic Pancreatic Cancer. N. Engl. J.
Med. 2011;364:1817–1825.
10.Von Hoff D.D., Ervin T., Arena F.P., Chiorean E.G., Infante
J., Moore M., Seay T., Tjulandin S.A., Ma W.W., Saleh
M.N., et al. Increased Survival in Pancreatic Cancer with
Nab-Paclitaxel plus Gemcitabine. N. Engl. J. Med.
2013;369:1691–1703.
11.Marthey L., Sa-Cunha A., Blanc J.F., Gauthier M., Cueff A.,
Francois E., Trouilloud I., Malka D., Bachet J.B., Coriat R.,
et al. FOLFIRINOX for Locally Advanced Pancreatic
Adenocarcinoma: Results of an AGEO Multicenter
Prospective Observational Cohort. Ann. Surg. Oncol.
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Sources, methods, and major patterns in GLOBOCAN
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13.Siegel, R. L., Miller, K. D. & Jemal, A. Cancer Statistics,

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2030: The Unexpected Burden of Thyroid, Liver, and
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0155 (2014).
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mortality rates for pancreatic cancer across the
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19.Petersen, G. M. et al. Pancreatic cancer genetic epidemiology

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20.Li, D., Xie, K., Wolff, R. & Abbruzzese, J. L. Pancreatic

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8 (2004).
21.Davis CH, Beane JD, Gazivoda VP, Grandhi MS,
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53
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ANNEXURES
AGE: WEIGHT: HEIGHT: BMI:

DOA: DOD:
CHIEF COMPALINTS: HISTORY OF PAST
ILLNESS:
PAST MEDICAL HISTORY: PAST MEDICATION

HISTORY:
SOCIAL HISTORY:
EDUCATION:
OCUUPATION: SMOKING
STATUS:ACTIVE/EX/NON SMOKER
DIET: ALCOHOL:
YES/NO
ALLERGIES: FAMILY
HISTORY:
GENERAL EXAMINATION: VITALS/PE

BP: SPO2: CNS:
TEMP: JVP: GIT:
PR: GRBS: CVS:

54
(J.N.T.U.H)
RR: LUNG:
DIAGNOSIS:
INDICATION:
LABORATORY INVESTIGATIONS
1st 2nd
cycle cycle
date Date
Sodium
Potassium
Chloride
BUN
Serum
Cretinine
Urea
Urine output
1st 2nd
cycle cycle
date: Date
Hemoglobin
RBC
WBC
PLATLET
COUNT
NEUTROPHILS
EOSINOPHILS
BASOPHILS
MPV
PDW
HCT

55
(J.N.T.U.H)
MCH
MCHC
BIOCHEMISTRY 1st 2nd

RBS cycle cycle
date: Date
F.B.S
P.P.B.S
TOTAL
BILIRUBIN
DIRECT
BILIRUBIN
INDIRECT
BILIRUBIN
S.G.O.T
S.G.O.P
ALK. PHOSPATE
SERUM ALBUMIN
SERUM
GLOBULIN
URIC ACID
ELECTROLYTES 1st 2nd

cycle cycle
date Date
SODIUM
POTASSIUM
BICARB
CHLORIDE
CALCIUM
PHOSPURUS

56
(J.N.T.U.H)
Chemotherapy at AIG
o Yes
o No
If no, name of Hospital :
________________________________________
Cycle number :
o 1
o 2
o 3
o 4
o 5
o 6
Date: ________________
Height : ________________
Weight : _________________kg
BSA : ___________________ kg/m2
Regimen :
o FOLFIRINOX
o GEMCITABINE +nab Paclitaxel
o Other
5-florouracil dose: _____________ mg/m2 ,
Any dose reduction
o Yes
o No
If yes % dose reduction compared to previous cycle

57
(J.N.T.U.H)
Irinotecan: _____________ mg/m2 ,

Any dose reduction
o Yes
o No
Oxaliplatin: _____________ mg/m2 ,
Any dose reduction
o Yes
o No
Anaemia
Grade
o 0
o 1
o 2
o 3
o 4
o 5
Neutropenia
Grade
o 0
o 1
o 2
o 3
o 4
o 5
Lymphopenia
Grade
o 0

58
(J.N.T.U.H)
o 1
o 2
o 3
o 4
o 5
Febrile neutropenia
Grade
o 3
o 4
o 5
Thrombocytopenia
Grade
o 0
o 1
o 2
o 3
o 4
o 5
GI Toxicity
o Yes
o No
Diarrhoea
Grade
o 0
o 1
o 2
o 3
o 4
o 5
Mucositis
Grade
o 0

59
(J.N.T.U.H)
o 1
o 2
o 3
o 4
o 5
Acute kidney injury
Grade
o 3
o 4
o 5
Gemcitabine dose: _____________ mg/m2 ,

Any dose reduction
o Yes
o No
Nab – paclitaxel : _____________ mg/m2 ,
Any dose reduction
o Yes
o No
Anaemia
Grade
o 0
o 1
o 2
o 3
o 4
o 5
Neutropenia

60
(J.N.T.U.H)
Grade
o 0
o 1
o 2
o 3
o 4
o 5
Lymphopenia
Grade
o 0
o 1
o 2
o 3
o 4
o 5
Febrile neutropenia
Grade
o 3
o 4
o 5
Thrombocytopenia
Grade
o 0
o 1
o 2
o 3
o 4
o 5
GI Toxicity
o Yes
o No

61
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Diarrhoea
Grade
o 0
o 1
o 2
o 3
o 4
o 5
Mucositis
Grade
o 0
o 1
o 2
o 3
o 4
o 5
Acute kidney injury
Grade
o 3
o 4
o 5

62
(J.N.T.U.H)

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A RETROSPECTIVE COMPARATIVE STUDY OF TOXICITIES AND OUTCOMES

BETWEEN GEMCITABINE + NAB PACLITAXEL AND FOLFIRINOX IN LOCALLY

Thesis submitted to Jawaharlal Nehru Technological University, Hyderabad in partial fulfilment of

SULTAN – UL – ULOOM COLLEGE OF PHARMACY

SULTAN-UL-ULOOM COLLEGE OF PHARMACY

This is to certify that the project work entitled “A RETROSPECTIVE

SULTAN-UL-ULOOM COLLEGE OF PHARMACY

This is to certify that the project work entitled “A RETROSPECTIVE

Signature of Guide Signature of External

SULTAN-UL-ULOOM COLLEGE OF PHARMACY

MARIAM ABDUL SAMAD H.T. NO – 18451T0006

MARIAM ABDUL SAMAD

2. Literature review 20-23

3. Aim and objective 24

DEPARTMENT OF PHARMACY PRACTICE SUCP

S.NO Abbreviations Explanation

DEPARTMENT OF PHARMACY PRACTICE SUCP

S.no Title Pg no.

DEPARTMENT OF PHARMACY PRACTICE SUCP

S.no Title Pg no.

DEPARTMENT OF PHARMACY PRACTICE SUCP

Neo adjuvant chemotherapy with Gemcitabine/nab-paclitaxel

Results:. The haematological toxicities rates were similar between

DEPARTMENT OF PHARMACY PRACTICE SUCP

The pancreas is a retroperitoneal gland located behind the greater

DEPARTMENT OF PHARMACY PRACTICE SUCP

DEPARTMENT OF PHARMACY PRACTICE SUCP

 Obesity and inactivity

DEPARTMENT OF PHARMACY PRACTICE SUCP

 Of bile, a substance produced in the liver. When

DEPARTMENT OF PHARMACY PRACTICE SUCP

pancreatic cells. Mutations in tumor suppressor genes (such as TP53,

DEPARTMENT OF PHARMACY PRACTICE SUCP

DEPARTMENT OF PHARMACY PRACTICE SUCP

 Stage I: The tumor is confined to the pancreas and measures

LOCALLY ADVANCED PANCREATIC CANCER

DEPARTMENT OF PHARMACY PRACTICE SUCP

Targeted therapies. Overall, understanding the genetic changes that

TREATMENT OPTIONS OF PANCREATIC CANCER

DEPARTMENT OF PHARMACY PRACTICE SUCP

 Surgery to remove the tumor. Different types of surgery are

 Distal pancreatectomy. This surgery is commonly done if

DEPARTMENT OF PHARMACY PRACTICE SUCP

o Total pancreatectomy. If the cancer has spread throughout

DEPARTMENT OF PHARMACY PRACTICE SUCP

 Stereotactic body radiation (SBRT) or cyber knife. These

NEOADJUVANT CHEMOTHERAPY OF LOCALLY

DEPARTMENT OF PHARMACY PRACTICE SUCP

The neo-adjuvant chemotherapy for locally advanced pancreatic

 Gemcitabine plus nab- paclitaxel ( GnP)

DEPARTMENT OF PHARMACY PRACTICE SUCP

DEPARTMENT OF PHARMACY PRACTICE SUCP

Pregnancy (teratogenic category): Category D.

DEPARTMENT OF PHARMACY PRACTICE SUCP

Drug Interactions: Paclitaxel metabolism may be affected by

DEPARTMENT OF PHARMACY PRACTICE SUCP

cerebrospinal fluid and brain

DEPARTMENT OF PHARMACY PRACTICE SUCP