Phase II Trial

Jeffrey A. Coderre,1 Eric H. Elowitz,2 Manjeet Chadha,3 Richard Bergland,2 Jacek Capala,1 Darrel D. Joel,1 Hungyuan B. Liu,1 Daniel N. Slatkin1 and Arjun D. Chanana1 1Medical Department Brookhaven National Laboratory, Upton, NY, 11973, USA; Departments of 2 ...

Introduction Cancer cervix is the second most common cancer
among women worldwide and is the cause of largest number of
cancer-related deaths among women in the developing countries.
In India cervical cancer is the commonest cancer among women
(126 000 new cases, 71 000 deaths around the year 2000). Due to
the lack of any population based screening in India nearly 80% of
the patients are detected at stage III or higher. There are trials
that do not conclusively prove that currently recommended
chemo-radiation will be equally effective in treating these large
number of advanced cases. With the objectives to evaluate
response and survival rates in patients with stage-III cervical
cancer treated with immunotherapy concomitant with
radiotherapy and compare the same with concomitant
chemo-radiation and to evaluate the safety of concomitant
immunotherapy and radiation this phase II trial was conducted by
Chittaranjan National Cancer Institute from 2008 to 2010 and
patients were followed up at 3 monthly intervals for 3 years.
Methods Stage III cervical cancer patients were randomized to study
arm (N = 104) or control arm (N = 105). In both arms the patients
received standard external beam radiation followed by brachytherapy.
In the study arm the patients received interferon-alpha 2b (3 mIU
subcutaneously thrice a week for 4 weeks) and retinoic acid (40 mg/
day orally for 30 days) starting from first day of radiation. Patients in
the control arm received cisplatin (40 mg/m2 once a week for
5 weeks) starting from first day of radiation. Patients were evaluated
for response 1 month after completion of treatment. They were
followed up every 3 months for 3 years or till death.
Results The study arms were comparable for demographic and
disease variables. Complete response was seen in 84.6% in study
arm and 80.0% in control arm (P = 0.47). The 3 years overall
survival was superior in the control arm (Log Rank analysis:
X2 = 7.93; P = 0.005). The study and the control arms were
comparable for disease-free survival (Log Rank analysis:
X2 = 2.69; P = 0.10). The most frequently observed grade 3/4
toxicities were anemia, neutropenia and gastro-intestinal toxicities,
which were significantly more frequent in chemo-radiation arm
compared to immuno-radiation arm.
Conclusions Immuno-radiation therapy had the same response
rate and disease-free survival as chemo-radiation but better
toxicity profile. The overall survival was inferior.

Background and purposeWe aim to report on local control in a phase II trial on preoperative hyperfractionated and accelerated radiotherapy schedule (HART) in locally advanced resectable rectal cancer (LARC). This fractionation schedule was designed to keep the overall treatment time (OTT) as short as possible.

To investigate three genetic alterations (TP53 mutation, Kras mutation and microsatellite instability (MSI)) and three polymorphisms (methylene tetrahydrofolate reductase (MTHFR) C677T, excision repair cross complementing group 1 (ERCC1)-118 and X-ray repair cross complementing group 1 (XRCC1)-399) for their ability to predict response, survival and toxicity to FOLFOX first line chemotherapy in the treatment of metastatic colorectal cancer (mCRC). Tumour tissues from 118 mCRC patients who underwent FOLFOX treatment from three successive phase II trials were evaluated for mutations in TP53 (exons 5-8) and Kras (codons 12 and 13) and for MSI using PCR-based analysis. Genotyping for common single nucleotide polymorphisms in the MTHFR (codon 677), ERCC1 (codon 118) and XRCC1 (codon 399) genes was also carried out using PCR techniques. These genetic markers were correlated with clinical response, survival and toxicity to treatment. Patients with the T allele of ERCC1-118 showed significa...

In this phase II, multicentre trial, patients with metastatic breast cancer (MBC) were treated with a combination of gemcitabine, epirubicin and paclitaxel (GET). The primary objective of this study was to determine the tolerability and activity in terms of complete responce (CR) and overall response rate of the GET combination in this patient population. Patients with no prior treatment for MBC, and at least one bidimensionally measurable lesion received gemcitabine 1000 mg m(-2) intravenously (i.v.) over 30 min on days 1 and 4, followed by epirubicin i.v. at 90 mg m(-2) on day 1, and paclitaxel 175 mg m(-2) over 3 h on day 1, every 21 days, up to eight courses. From May 1999 to June 2000, 48 patients were enrolled from seven Italian institutions. A total of 297 chemotherapy courses were administered with a median of six cycles patient(-1) (range 1-8). Seven patients (15%) obtained CR and 27 patients (56%) had partial responce, for an overall response rate of 71% (95% CI: 58.3-83.7...

Our goal was to determine if a healing flare response seen on bone scintigraphy occurs following chemotherapy with Taxol (paclitaxel; Bristol-Myers Squibb Co., Princeton, NJ), a novel antimicrotubule agent for metastatic breast cancer. We performed 74 bone scans on 21 females with breast cancer and bone metastases entering a Phase II trial of Taxol chemotherapy with granulocyte colony stimulating factor (G-CSF). All patients had baseline scans within 6 wk prior to therapy, after the second cycle (4-6 wk) of Taxol, and then after 6-12 mo. All bone scans were reviewed by two nuclear medicine physicians, without knowledge of the patients' clinical history. Skeletal radiographs, CT and MRI scans, as well as clinical history were compared with scan findings. Seven of the 21 patients showed improvement in bone scan findings. Of these seven, three had a flare response following two cycles (4-6 wk) of Taxol, characterized by increased activity in baseline lesions and the appearance of n...