Cancer incidence and mortality is increasing in the developing world. Inequities between low-, mi... more Cancer incidence and mortality is increasing in the developing world. Inequities between low-, middle-, and high-income countries affect disease burden and the infrastructure needs in response to cancer. We surveyed early-career oncologists attending workshops in clinical research in three countries with emerging economies about their perception of the evolving cancer burden. A cross-sectional survey questionnaire was distributed at clinical trial concept development workshops held in Beijing, Lahore, Karachi, and Mumbai at major hospitals to acquire information regarding home-country health conditions and needs. A total of 100 respondents participated in the workshops held at major hospitals in the region (India = 29, China = 25, Pakistan = 42, and other = 4). Expected consensus on many issues (e.g., emergence of cancer as a significant health issue) was balanced with significant variation in priorities, opportunities, and challenges. Chinese respondents prioritized improvements in...
Most patients with incurable cancer want information about the impact cancer will have on their f... more Most patients with incurable cancer want information about the impact cancer will have on their future, and many want specific estimates of the most likely, best case, and worst case scenarios for survival. With improved understanding of life expectancy, patients are better equipped to make appropriate treatment decisions and plans for the future. Although physicians acknowledge that patients with incurable cancer want prognostic information and benefit from this, most struggle to provide it and experience difficulty in making reliable estimates, communicating them, and tailoring the information to the individual patient. In this review we address some of the implications that arise from thinking and talking about life expectancy with people who have incurable cancer, particularly those considering first- or second-line chemotherapy.
Docetaxel administered 3-weekly with cisplatin and 5-fluorouracil leads to better survival than d... more Docetaxel administered 3-weekly with cisplatin and 5-fluorouracil leads to better survival than does standard therapy in patients with oesophagogastric cancer, but leads to high rates of haematological toxicity. Weekly docetaxel is associated with less haematological toxicity. This randomised phase II study tested weekly docetaxel-based combination chemotherapy regimens, with the aim of maintaining their activity while reducing toxicity. Patients with histologically confirmed metastatic oesophageal or gastric carcinoma were randomised to receive weekly docetaxel (30 mg m(-2)) on days 1 and 8, cisplatin (60 mg m(-2)) on day 1, and 5-fluorouracil (200 mg m(-2) per day) continuously, every 3 weeks (weekly TCF, wTCF); or docetaxel (30 mg m(-2)) on days 1 and 8 and capecitabine (1600 mg m(-2) per day) on days 1-14, every 3 weeks (weekly TX, wTX). A total of 106 patients were enrolled (wTCF, n=50; wTX, n=56). Response rates, the primary end point, were 47% with wTCF and 26% with wTX. Rate...
Hepatocellular carcinoma (primary liver cancer) is the third commonest cause of cancer mortality ... more Hepatocellular carcinoma (primary liver cancer) is the third commonest cause of cancer mortality world-wide. Survival is poor for patients with advanced disease. Trials of tamoxifen for hepatocellular carcinoma have conflicting results. To conduct a systematic review of the literature to assess the effect of tamoxifen on overall survival, quality-of-life, tumour response, and treatment toxicity in people with advanced hepatocellular carcinoma. We identified trials from The Cochrane Hepato-Biliary Group Controlled Trials Register (January 2004), The Cochrane Central Register of Controlled Trials on The Cochrane Library (Issue 3, 2003), and MEDLINE database (1966 to November 2003). We searched bibliographies of review articles and identified trials, and hand-searched abstracts from relevant other meetings. All randomised clinical trials of treatment with tamoxifen compared to a control treatment without tamoxifen in people with hepatocellular carcinoma, including trials of tamoxifen versus placebo, tamoxifen versus best supportive care, and tamoxifen plus other treatment versus the same other treatment alone. Three independent reviewers selected studies for inclusion, rated them for methodologic quality components (generation of allocation sequence; allocation concealment; blinding; and follow-up), and extracted data on the specified outcomes. Hazard ratios were derived for overall survival where possible. Meta-analysis was performed using a fixed-effect model. Ten randomised trials randomising 1709 patients were included. Tamoxifen versus placebo/no intervention had no significant effect on overall survival (hazard ratio 1.05; 95% CI 0.94 to 1.16; P = 0.4). This comparison showed no statistical heterogeneity (P = 0.2 and I(2 ) = 25.9%). Subgroup analysis showed that tamoxifen tended to increase mortality in trials with three adequate/three methodological components (hazard ratio 1.15; 95% CI 0.99 to 1.34; P = 0.06), showed no significant effect in trials with two adequate/three methodological components (hazard ratio 1.00; 95% CI 0.84 to 1.18; P = 0.98), and tended to reduce mortality in trials with one or less adequate/three methodological components (hazard ratio 0.82; 95% CI 0.60 to 1.12; P = 0.2), although this may have been confounded by the use of higher doses of tamoxifen in the better quality trials. Tamoxifen was associated with adverse effects. One trial measured patient quality of life, but the results were not reported in detail. These data do not support the use of tamoxifen for patients with hepatocellular carcinoma. Further research on the effects of tamoxifen in hepatocellular carcinoma does not seem warranted.
To systematically review studies of antiemetics used in the treatment of nausea in patients with ... more To systematically review studies of antiemetics used in the treatment of nausea in patients with far-advanced cancer. Randomized controlled trials (RCT) and uncontrolled studies identified by electronic and hand searching. Identified studies were appraised for quality and effect size. Of 21 studies included, 2 were systematic reviews, 7 were RCT and 12 were uncontrolled studies or case series. Differences in interventions and outcomes amongst the RCT precluded any quantitative data synthesis and all seven studies were prone to bias. Whereas uncontrolled studies indicated a high response rate to standard regimens (75-93% for both nausea and vomiting), RCT showed much lower response rates to these agents (23-36% for nausea, 18-52% for vomiting). The two methods of antiemetic choice (choice based either on the inferred mechanism or empirical) were equally effective. There is reasonably strong evidence for the use of metoclopramide in cancer-associated dyspepsia and steroids in malignant bowel obstruction. There was conflicting evidence about the efficacy of serotonin antagonists compared with standard treatments (e.g. metoclopramide, dopamine antagonists and dexamethasone). There was little or no evidence of the efficacy of some commonly used and seemingly effective drugs such as haloperidol, cyclizine, and methotrimeprazine. Evidence supporting the existing consensus-based guidelines for management of nausea and vomiting in advanced cancer is sparse. Current approaches to treatment based on the neuropharmacology of the emetic pathway may be inappropriate in this setting. Well-designed studies of the impact of "standard" management and novel agents on nausea and vomiting in palliative populations are needed.
This survey aimed to provide a symptom profile, in particular for nausea and its treatment, of ad... more This survey aimed to provide a symptom profile, in particular for nausea and its treatment, of advanced cancer patients prior to implementation of a clinical practice guideline for nausea. An audit of 82 advanced cancer patients admitted to a major Australian teaching hospital was undertaken. While nausea was present in 26 (32%) of respondents, antiemetics were prescribed in 52 (68%), a higher proportion than in the past, and being taken by 32 (39%). Patients reporting moderate-to-severe nausea often missed out on treatment. These findings underscore the need for more attention to education of hospital staff in the assessment and treatment of this frequently bothersome symptom, and raise issues for study design of symptom control research.
We sought the attitudes of people with a cancer experience to using best case, worst case, and ty... more We sought the attitudes of people with a cancer experience to using best case, worst case, and typical scenarios for survival to explain life expectancy. Oncology clinic attendees and Breast Cancer Network Australia (BCNA) members completed a survey describing two formats for explaining life expectancy to a hypothetical patient with advanced cancer-providing either three scenarios for survival or just the median survival time. Characteristics of the 505 respondents from outpatient clinics (n = 251) and BCNA (n = 254) were median age of 58 years, female 74 %, and breast primary 64 %. More respondents agreed that explaining three scenarios (vs. median survival) would make sense (93 vs. 75 %), be helpful (93 vs. 69 %), convey hope (68 vs. 44 %), and reassure (60 vs. 40 %), while fewer respondents agreed that explaining three scenarios (vs. median survival) would upset people (24 vs. 36 %); all p values < 0.001. Most respondents agreed that each scenario should be presented: best case 89 %, worst case 82 %, and typical 92 %. For information about their own prognosis, 88 % preferred all three scenarios and 5 % a single estimate of the median. Respondents with higher education were more likely to agree that presenting three scenarios would be helpful (95 vs. 90 %, p = 0.05). Respondents with breast cancer were more likely to agree that explaining three scenarios would upset people (31 vs. 13 %, p < 0.001). Most respondents judged presentation of best case, worst case, and typical scenarios preferable and more helpful and reassuring than presentation of just the median survival time when explaining life expectancy to patients with advanced cancer.
The hurdle of cost effectiveness for the selection and reimbursement of drugs in Australia limits... more The hurdle of cost effectiveness for the selection and reimbursement of drugs in Australia limits access to new medicines based on an assessment of cost relative to clinical benefit. Those drugs that are expensive and provide modest benefits will be less likely to receive a government price subsidy. There is concern that the cost-effectiveness hurdle will limit access to new cancer treatments because of their high costs and modest benefits. To test the hypothesis that Ceteris paribus, cancer drugs are less likely to receive a recommendation for reimbursement on the Pharmaceutical Benefits Scheme (PBS) than non-cancer drugs. We reviewed public summary documents (PSDs) on all major submissions considered by the Pharmaceutical Benefits Advisory Committee (PBAC) from July 2005 to March 2008. Each PSD includes summary information on the clinical, economic and utilization considerations of the PBAC in arriving at a recommendation. A total of 227 PSDs were reviewed, from which 243 PBAC recommendations were identified. Logistic regression was used to determine the effects of drug type (cancer vs non-cancer) and other potentially confounding variables on the outcome of PBS approval versus non-approval. There were 243 PBAC recommendations in 227 published PSDs: 108 for rejection (44%), 10 deferrals (4%) and 125 (51%) recommendations for listing. Recommendations for listing were made somewhat more often for non-cancer drugs than for cancer drugs: 104/191 (54%) versus 21/52 (40%), respectively; p = 0.07. Based on the results for univariable analyses, there is evidence that four variables have some association (p < 0.25) with PBAC approval, but only type of application, economic modelling and estimated cost to the PBS remained statistically significant at p < 0.05 in the multivariable model. No interaction terms were statistically significant. Cancer drug submissions tend to have a modelled economic evaluation and have a higher cost per QALY than non-cancer drugs (29% vs 15% of cancer and non-cancer drugs, respectively had a reported modelled cost per QALY of more than Australian dollars [$A]45 000; p < 0.001). Submissions that include a modelled economic evaluation and have a higher cost per QALY get approved less often than submissions without an economic modelling (p = 0.04). However, after adjusting for economic modelling, there is no statistical difference between cancer and non-cancer drugs in terms of gaining recommendation for PBS listing. The PBAC applies decision criteria equitably to cancer and non-cancer drugs, in that cancer drugs are neither favoured nor disadvantaged but they are more expensive and target a smaller population than non-cancer drugs. Further debate and research is needed to determine society's willingness to pay for a QALY and whether this differs between drugs for cancer and other indications or for interventions that differ on criteria other than cost effectiveness.
Cancer incidence and mortality is increasing in the developing world. Inequities between low-, mi... more Cancer incidence and mortality is increasing in the developing world. Inequities between low-, middle-, and high-income countries affect disease burden and the infrastructure needs in response to cancer. We surveyed early-career oncologists attending workshops in clinical research in three countries with emerging economies about their perception of the evolving cancer burden. A cross-sectional survey questionnaire was distributed at clinical trial concept development workshops held in Beijing, Lahore, Karachi, and Mumbai at major hospitals to acquire information regarding home-country health conditions and needs. A total of 100 respondents participated in the workshops held at major hospitals in the region (India = 29, China = 25, Pakistan = 42, and other = 4). Expected consensus on many issues (e.g., emergence of cancer as a significant health issue) was balanced with significant variation in priorities, opportunities, and challenges. Chinese respondents prioritized improvements in...
Most patients with incurable cancer want information about the impact cancer will have on their f... more Most patients with incurable cancer want information about the impact cancer will have on their future, and many want specific estimates of the most likely, best case, and worst case scenarios for survival. With improved understanding of life expectancy, patients are better equipped to make appropriate treatment decisions and plans for the future. Although physicians acknowledge that patients with incurable cancer want prognostic information and benefit from this, most struggle to provide it and experience difficulty in making reliable estimates, communicating them, and tailoring the information to the individual patient. In this review we address some of the implications that arise from thinking and talking about life expectancy with people who have incurable cancer, particularly those considering first- or second-line chemotherapy.
Docetaxel administered 3-weekly with cisplatin and 5-fluorouracil leads to better survival than d... more Docetaxel administered 3-weekly with cisplatin and 5-fluorouracil leads to better survival than does standard therapy in patients with oesophagogastric cancer, but leads to high rates of haematological toxicity. Weekly docetaxel is associated with less haematological toxicity. This randomised phase II study tested weekly docetaxel-based combination chemotherapy regimens, with the aim of maintaining their activity while reducing toxicity. Patients with histologically confirmed metastatic oesophageal or gastric carcinoma were randomised to receive weekly docetaxel (30 mg m(-2)) on days 1 and 8, cisplatin (60 mg m(-2)) on day 1, and 5-fluorouracil (200 mg m(-2) per day) continuously, every 3 weeks (weekly TCF, wTCF); or docetaxel (30 mg m(-2)) on days 1 and 8 and capecitabine (1600 mg m(-2) per day) on days 1-14, every 3 weeks (weekly TX, wTX). A total of 106 patients were enrolled (wTCF, n=50; wTX, n=56). Response rates, the primary end point, were 47% with wTCF and 26% with wTX. Rate...
Hepatocellular carcinoma (primary liver cancer) is the third commonest cause of cancer mortality ... more Hepatocellular carcinoma (primary liver cancer) is the third commonest cause of cancer mortality world-wide. Survival is poor for patients with advanced disease. Trials of tamoxifen for hepatocellular carcinoma have conflicting results. To conduct a systematic review of the literature to assess the effect of tamoxifen on overall survival, quality-of-life, tumour response, and treatment toxicity in people with advanced hepatocellular carcinoma. We identified trials from The Cochrane Hepato-Biliary Group Controlled Trials Register (January 2004), The Cochrane Central Register of Controlled Trials on The Cochrane Library (Issue 3, 2003), and MEDLINE database (1966 to November 2003). We searched bibliographies of review articles and identified trials, and hand-searched abstracts from relevant other meetings. All randomised clinical trials of treatment with tamoxifen compared to a control treatment without tamoxifen in people with hepatocellular carcinoma, including trials of tamoxifen versus placebo, tamoxifen versus best supportive care, and tamoxifen plus other treatment versus the same other treatment alone. Three independent reviewers selected studies for inclusion, rated them for methodologic quality components (generation of allocation sequence; allocation concealment; blinding; and follow-up), and extracted data on the specified outcomes. Hazard ratios were derived for overall survival where possible. Meta-analysis was performed using a fixed-effect model. Ten randomised trials randomising 1709 patients were included. Tamoxifen versus placebo/no intervention had no significant effect on overall survival (hazard ratio 1.05; 95% CI 0.94 to 1.16; P = 0.4). This comparison showed no statistical heterogeneity (P = 0.2 and I(2 ) = 25.9%). Subgroup analysis showed that tamoxifen tended to increase mortality in trials with three adequate/three methodological components (hazard ratio 1.15; 95% CI 0.99 to 1.34; P = 0.06), showed no significant effect in trials with two adequate/three methodological components (hazard ratio 1.00; 95% CI 0.84 to 1.18; P = 0.98), and tended to reduce mortality in trials with one or less adequate/three methodological components (hazard ratio 0.82; 95% CI 0.60 to 1.12; P = 0.2), although this may have been confounded by the use of higher doses of tamoxifen in the better quality trials. Tamoxifen was associated with adverse effects. One trial measured patient quality of life, but the results were not reported in detail. These data do not support the use of tamoxifen for patients with hepatocellular carcinoma. Further research on the effects of tamoxifen in hepatocellular carcinoma does not seem warranted.
To systematically review studies of antiemetics used in the treatment of nausea in patients with ... more To systematically review studies of antiemetics used in the treatment of nausea in patients with far-advanced cancer. Randomized controlled trials (RCT) and uncontrolled studies identified by electronic and hand searching. Identified studies were appraised for quality and effect size. Of 21 studies included, 2 were systematic reviews, 7 were RCT and 12 were uncontrolled studies or case series. Differences in interventions and outcomes amongst the RCT precluded any quantitative data synthesis and all seven studies were prone to bias. Whereas uncontrolled studies indicated a high response rate to standard regimens (75-93% for both nausea and vomiting), RCT showed much lower response rates to these agents (23-36% for nausea, 18-52% for vomiting). The two methods of antiemetic choice (choice based either on the inferred mechanism or empirical) were equally effective. There is reasonably strong evidence for the use of metoclopramide in cancer-associated dyspepsia and steroids in malignant bowel obstruction. There was conflicting evidence about the efficacy of serotonin antagonists compared with standard treatments (e.g. metoclopramide, dopamine antagonists and dexamethasone). There was little or no evidence of the efficacy of some commonly used and seemingly effective drugs such as haloperidol, cyclizine, and methotrimeprazine. Evidence supporting the existing consensus-based guidelines for management of nausea and vomiting in advanced cancer is sparse. Current approaches to treatment based on the neuropharmacology of the emetic pathway may be inappropriate in this setting. Well-designed studies of the impact of "standard" management and novel agents on nausea and vomiting in palliative populations are needed.
This survey aimed to provide a symptom profile, in particular for nausea and its treatment, of ad... more This survey aimed to provide a symptom profile, in particular for nausea and its treatment, of advanced cancer patients prior to implementation of a clinical practice guideline for nausea. An audit of 82 advanced cancer patients admitted to a major Australian teaching hospital was undertaken. While nausea was present in 26 (32%) of respondents, antiemetics were prescribed in 52 (68%), a higher proportion than in the past, and being taken by 32 (39%). Patients reporting moderate-to-severe nausea often missed out on treatment. These findings underscore the need for more attention to education of hospital staff in the assessment and treatment of this frequently bothersome symptom, and raise issues for study design of symptom control research.
We sought the attitudes of people with a cancer experience to using best case, worst case, and ty... more We sought the attitudes of people with a cancer experience to using best case, worst case, and typical scenarios for survival to explain life expectancy. Oncology clinic attendees and Breast Cancer Network Australia (BCNA) members completed a survey describing two formats for explaining life expectancy to a hypothetical patient with advanced cancer-providing either three scenarios for survival or just the median survival time. Characteristics of the 505 respondents from outpatient clinics (n = 251) and BCNA (n = 254) were median age of 58 years, female 74 %, and breast primary 64 %. More respondents agreed that explaining three scenarios (vs. median survival) would make sense (93 vs. 75 %), be helpful (93 vs. 69 %), convey hope (68 vs. 44 %), and reassure (60 vs. 40 %), while fewer respondents agreed that explaining three scenarios (vs. median survival) would upset people (24 vs. 36 %); all p values < 0.001. Most respondents agreed that each scenario should be presented: best case 89 %, worst case 82 %, and typical 92 %. For information about their own prognosis, 88 % preferred all three scenarios and 5 % a single estimate of the median. Respondents with higher education were more likely to agree that presenting three scenarios would be helpful (95 vs. 90 %, p = 0.05). Respondents with breast cancer were more likely to agree that explaining three scenarios would upset people (31 vs. 13 %, p < 0.001). Most respondents judged presentation of best case, worst case, and typical scenarios preferable and more helpful and reassuring than presentation of just the median survival time when explaining life expectancy to patients with advanced cancer.
The hurdle of cost effectiveness for the selection and reimbursement of drugs in Australia limits... more The hurdle of cost effectiveness for the selection and reimbursement of drugs in Australia limits access to new medicines based on an assessment of cost relative to clinical benefit. Those drugs that are expensive and provide modest benefits will be less likely to receive a government price subsidy. There is concern that the cost-effectiveness hurdle will limit access to new cancer treatments because of their high costs and modest benefits. To test the hypothesis that Ceteris paribus, cancer drugs are less likely to receive a recommendation for reimbursement on the Pharmaceutical Benefits Scheme (PBS) than non-cancer drugs. We reviewed public summary documents (PSDs) on all major submissions considered by the Pharmaceutical Benefits Advisory Committee (PBAC) from July 2005 to March 2008. Each PSD includes summary information on the clinical, economic and utilization considerations of the PBAC in arriving at a recommendation. A total of 227 PSDs were reviewed, from which 243 PBAC recommendations were identified. Logistic regression was used to determine the effects of drug type (cancer vs non-cancer) and other potentially confounding variables on the outcome of PBS approval versus non-approval. There were 243 PBAC recommendations in 227 published PSDs: 108 for rejection (44%), 10 deferrals (4%) and 125 (51%) recommendations for listing. Recommendations for listing were made somewhat more often for non-cancer drugs than for cancer drugs: 104/191 (54%) versus 21/52 (40%), respectively; p = 0.07. Based on the results for univariable analyses, there is evidence that four variables have some association (p < 0.25) with PBAC approval, but only type of application, economic modelling and estimated cost to the PBS remained statistically significant at p < 0.05 in the multivariable model. No interaction terms were statistically significant. Cancer drug submissions tend to have a modelled economic evaluation and have a higher cost per QALY than non-cancer drugs (29% vs 15% of cancer and non-cancer drugs, respectively had a reported modelled cost per QALY of more than Australian dollars [$A]45 000; p < 0.001). Submissions that include a modelled economic evaluation and have a higher cost per QALY get approved less often than submissions without an economic modelling (p = 0.04). However, after adjusting for economic modelling, there is no statistical difference between cancer and non-cancer drugs in terms of gaining recommendation for PBS listing. The PBAC applies decision criteria equitably to cancer and non-cancer drugs, in that cancer drugs are neither favoured nor disadvantaged but they are more expensive and target a smaller population than non-cancer drugs. Further debate and research is needed to determine society's willingness to pay for a QALY and whether this differs between drugs for cancer and other indications or for interventions that differ on criteria other than cost effectiveness.
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