- Email: [email protected]
Good manners for the pharmaceutical industry
THE LANCET
Good manners for the pharmaceutical industry SIR—The results of two randomised studies of cisplatin-cyclophosphamide versus cisplatin-paclitaxel in advanced epithelial ovarian cancer are now available (Gynecologic Oncology Group trial no 111 and the Intergroup trial).1,2 Your June 7 editorial3 makes two inaccurate statements: these studies are not “relatively small” since their combined total is over 1000 patients, and to describe the Intergroup results as preliminary is misleading since it implies that the interpretation may change with further follow-up. This is unlikely because the primary endpoint is progression-free survival and 469 events have occurred (data presented in May, 1997, at the American Society for Clinical Oncology meeting). Response rates and progression-free survival show an impressive advantage for cisplatinpaclitaxel (table). A third study, also presented at ASCO, GOG no 132,4 randomised patients to cisplatin-paclitaxel or singleagent cisplatin or paclitaxel. Response rates to single-agent paclitaxel were significantly lower than those observed in the other two arms, but there was no difference between the three in terms of progression-free or overall survival. This trial has been used to justify not adopting cisplatin-paclitaxel as standard. However, in GOG-132 half the patients crossed over to one of the other treatment groups and this sometimes happened before progression was documented, which calls into question the progression-free survival data. GOG132 is therefore essentially a study of sequential cisplatin-paclitaxel versus first-line treatment with the two drugs combined. It has been difficult to demonstrate an overall survival benefit for individual chemotherapy agents in ovarian cancer because of the relative salvage effect of “crossover” treatment. Advanced Ovarian Cancer Trialists Group5 metaanalysis failed to prove a survival benefit for platinum-based regiments compared with non-platinum-based chemotherapy yet everyone accepts Treatment
platinum as standard. This explains the excitement over GOG-111 and the immediate adoption of the cisplatinpaclitaxel regimen in some quarters. We were unhappy with this change, based on only one trial, and said so at the International Gynaecological Cancer Society in September, 1995. ICON 3 was designed to detect a 10% difference in 2-year survival. 1254 patients have been recruited but with only about 100 events, there is little to analyse. The data monitoring committee has recommended a further 800 patients to allow 4–5% difference in survival to be detected and to permit subset analysis of the two treatments on the main prognostic indicator, the bulk of residual disease after initial surgery. If we assume a range of possible 5-year survivals of 40% down to 15%, a 50% baseline survival at two years (ICON 3 protocol), and statistical power of 90% we calculate that only a 1–2% extra survival benefit can be detected by the addition of 800 patients. The AOCTG overview strongly suggests that carboplatin and cisplatin are of similar efficacy5 (updated by L Stewart in 1997) and there are obvious advantages to carboplatin including reduced neurotoxicity, ototoxicity, and renal toxicity and avoidance of intravenous hydration before and after treatment. Also single-arm carboplatin-paclitaxel dose-escalation phase I/II studies show this to be a well-tolerated regimen. The problem facing ICON 3 investigators is that two good trials already show an impressive advantage in terms of response rates and progression-free survival for cisplatin-paclitaxel over a standard platinum combination regimen. First-line treatment with carboplatin-paclitaxel could therefore be advocated with its low toxicity. ICON 3 is an important trial but crossover treatment may confound the survival data and a further 800 patients are not going to help with the statistical evaluation of any impact on survival. *Martin Gore, Roger A’Hern, Kenneth Swenerton *Royal Marsden Hospital, London SW3 6JJ, UK; and BC Cancer Agency, Vancouver Cancer Centre, BC, Canada
Responses
Progression-free survival
No
%
HR (95% CI)
p
No
Median mo
HR (95% CI)
GOG 111 PC PP
116 100
60 73
Intergroup PC PP
151 149
Overall PC PP
267 249
p
1·76 (1·00–3·09)
<0·05
202 184
13 18
0·7 (0·5–0·8)
<0·001
66 77
1·71 (1·04–2·83)
<0·05
330 338
11 14
0·66 (0·52–0·77)
<0·0001
64 75
1·73 (1·19–2·52)
<0·004
532 522
.. ..
0·68 (0·58–0·79)
<0·000001
PC=cisplatin-cyclophosphamide, PP=cisplatin-paclitaxel, HR=hazard ratio (and 95 % confidence interval).
Response rates and progression-free survival in GOG-111 and Intergroup studies
370
1
2
3
4
5
McGuire WP, Hoskins WJ, Brady MF, et al. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med 1996; 334: 1–6. Piccart MJ, Bertelsen K, Stuart G, et al. Is cisplatin-paclitaxel the standard in first-line treatment of advanced ovarian cancer? The EORTC-GCCG, NOCOVA, NCI-C and Scottish intergroup experience. Proc ASCO 1997; 16: 1258. Editorial. Good manners for the pharmaceutical industry. Lancet 1997; 349: 1635. Muggia FM, Braly PS, Brady MF, et al. Phase III of cisplatin or paclitaxel, versus their combination in suboptimal stage III and IV epithelial ovarian cancer: Gynecologic Oncology Group study 132. Proc ASCO 1997; 16: 1257. Advanced Ovarian Cancer Trialists Group. Chemotherapy in advanced ovarian cancer: an overview of randomised clinical trials. BMJ 1991; 303: 884–93.
SIR—Your June 7 editorial,1 discusses the negative response of Bristol-Myers Squibb to the recommendation by the independent data monitoring committee that the ICON 3 trial should continue. In this trial patients with epithelial ovarian cancer are randomised to receive paclitaxel plus carboplatin or an appropriate platinum control. As one of the larger contributors to the ICON 3 trial, I wish to disagree with the position taken by Bristol-Myers Squibb. The presentation of early data from the Intergroup study2 at the American Society of Clinical Oncology meeting in May, 1997, which confirmed the improvement in progression-free survival study previously shown by the GOG-111 trial3 lends support to the use of paclitaxel in the first-line treatment of patients with epithelial ovarian cancer. However, the publication of data from GOG-1324 at the same meeting demonstrated just how difficult it is to draw conclusions from the results of individual clinical trials. In GOG-132 patients with advanced disease were randomised three ways, and received full-dose single agent cisplatin, paclitaxel 200 mg/m2 given as a 24-h infusion, or a combination of cisplatin and paclitaxel as used previously in GOG-111. Progression-free survival for the two platinum containing arms of the trial was significantly better than in the single agent paclitaxel arm (11·4 months), but there was no difference between single-agent cisplatin and the cisplatin-paclitaxel combination (16·4 and 14·1 months, respectively). There was no difference between the three arms in the survival analysis (paclitaxel 25·9 months, cisplatin 30·2 months, cisplatin-paclitaxel 26·6 months). One of the main differences between GOG132 and both the Intergroup study and GOG-111 is the widespread use of paclitaxel as a salvage treatment. In the UK carboplatin is the most
Vol 350 • August 2, 1997
THE LANCET
widespread standard chemotherapy treatment for ovarian cancer. Previous trials have not been able to show any significant difference in efficiency between single-agent cisplatin and single-agent carboplatin. Carboplatin is of course virtually devoid of the troublesome gastrointestinal and neurotoxicity associated with cisplatin in GOG-132. Within ICON 3, single-agent carboplatin is one of the available control arms and will therefore provide vital data on this comparison. It may indeed turn out that the combination of a platinum drug with paclitaxel is better than standard platinum-based therapy. But if non-responders can be salvaged by the use of paclitaxel later on then this may be a more efficient use of scarce health service resources, particularly since the excess treatment cost of the paclitaxel containing regimen is in the region of £9000. I believe that the ICON 3 trial has to continue in order to provide information that will help to answer these issues. A 2000 patient trial which includes quality-of-life assessment will provide us with extremely valuable and robust information on which we may base our clinical and research decisions for the years to come. It will also provide vital information to those responsible for commissioning health care in the future. Timothy Perren ICRF Cancer Medicine Research Unit, St James’s University Hospital, Leeds LS9 7TF, UK
1
2
3
4
Editorial. Good manners for the pharmaceutical industry. Lancet 1997; 349: 1635. Piccart MJ, Bertelsen K, Stuart G, et al. Is cisplatin-Paclitaxel (P-T) the standard in first-line treatment of advanced ovarian cancer (Ov Ca)? The EORTC-GCCG, NOCOVA, NCI-C and Scottish intergroup experience. Procs Am Soc Clin Oncol 1997; 16: 352a. McGuire WP, Hoskins WJ, Brady MF, et al. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage 111 and stage IV ovarian cancer (see comments). N Engl J Med 1996; 334: 1–6. Muggia FM, Braley PS, Brady MF, et al. Phase 111 of cisplatin (P) or paclitaxel (T), versus their combination in suboptimal stage 111 and IV epithelial ovarian cancer (EOC): Gynecologic Oncology Group. Procs Am Soc Clin Oncol 1997; 16: 352a.
no affect on representatives of the two largest accruing centres as to whether the trial should continue. When we first heard that the Intergroup study had confirmed that patients in the paclitaxel group showed improvement in progression free survival, as previously reported by the Gynaecologic Oncology Group, our initial reaction was that the ICON 3 trial should stop. We wish to explain why we have changed our minds. It is possible that the ICON 3 trial already shows a significant improvement in progression free survival in the paclitaxel group. However, if the improvement in progression free survival of adding paclitaxel in the three trials only amounts to a few months, this may be insufficient benefit to persuade purchasers to provide an extra £9000 for each patient with ovarian cancer. The Intergroup trial has not yet divulged any survival data, and we presume that the data monitoring committee recommended the continuation of ICON 3 because there is not yet a highly significant difference in survival between the paclitaxel group and controls. Unlike the situation in the USA, only a small proportion of our patients who have a relapse are crossing over to paclitaxel, which will allow us to see the effect of paclitaxel on survival. Unless the Intergroup and ICON 3 trials show an improvement in survival sufficient to persuade purchasers to provide more money for cytotoxic chemotherapy, we will not be able to use paclitaxel for NHS patients. It is essential that NHS Regional Research and Development insist that all purchasers fund paclitaxel for this trial, otherwise the trial will stop recruiting UK patients in the UK because of inadequate funding and not because of pressure from Bristol-Myers Squibb. Patients would be the ultimate losers because without reliable data showing whether paclitaxel improves survival, how can they decide whether it is worth losing their hair? *Gordon J S Rustin, Derek Crowther *Centre for Cancer Treatment, Mouth Vernon Hospital, Northwood, Middlesex HA6 2RN, UK; and CRC Department of Medical Oncology, Christie Hospital, Manchester
1
SIR—Your June 7 editorial1 discusses the manners of Bristol-Myers Squibb over the continuation of the third International Collaboration on Ovarian Neoplasm study (ICON 3), in which patients with epithelial ovarian cancer are randomised to receive paclitaxel plus carboplatin or an appropriate platinum control. The media interest inhibited discussion at the open meeting in London on June 2, but had
Vol 350 • August 2, 1997
Editorial. Good manners for the pharmaceutical industry. Lancet 1997; 349: 1635.
SIR—Your June 7 editorial1 justifiably draws attention to the value of large randomised trials of cancer treatment and to the dangers of drawing premature conclusions on new treatments. However, to say that the decision of the Data Monitoring Committee to continue the ICON 3 study to recruit up to 2000 patients should not be debated is unreasonable.
There is a substantial amount of data from randomised trials of paclitaxel in ovarian cancer. As with any series of clinical investigations, many different interpretations are possible. Although arguments in favour of continuing recruitment to ICON 3 can certainly be marshalled, concern over this is understandable because some important points have not, to our knowledge, been clearly answered. What is the statistical probability that the existing randomised studies that show an advantage for paclitaxel are wrong? To what degree was the survival in the cisplatin only group of the GOG132 study affected by second-line treatment with taxanes, and was the serious toxicity observed in this highdose platinum group justifiable? Will the information on these new studies be included in the consent form for patients entering ICON 3? Even the most pessimistic interpretation of the current data still suggests that the overall survival of patients with advanced ovarian cancer is enhanced by the use of paclitaxel given at relapse. Continuation of recruitment to ICON 3 should be conditional on this treatment being available to all patients who are allocated to the control group of this study. *Hilary Calvert, Stan Kaye, Richard Osborne, Karol Sikora, Hilary Thomas *Department of Oncology, University of Newcastle, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE, UK; Department of Medical Oncology, Beatson Institute, University of Glasgow, Glasgow; Dorset Cancer Centre, Poole Hospital Health Trust, Poole; and Department of Clinical Oncology, Royal Postgraduate Medical School, London
1
Editorial. Good manners for the pharmaceutical industry. Lancet 1997; 349: 1635.
Health impact of human rights violations in Haitian refugees SIR—After the 1991 coup in Haiti, extreme oppression by the military resulted in over 40 000 Haitians fleeing the country. During their flight, those intercepted at sea by the US Coast Guard were detained at a naval base in Guantanamo Bay, Cuba. At Guantanamo Bay, the refugees were further exposed to an insecure and unsanitary living environment. Between June, 1992, and October, 1995, we interviewed refugees who had been detained in Guantanamo Bay and were receiving assistance for asylum claims from a legal services agency in the USA. 19 refugees were randomly selected, and 15 (80%)
371
Good manners for the pharmaceutical industry SIR—The results of two randomised studies of cisplatin-cyclophosphamide versus cisplatin-paclitaxel in advanced epithelial ovarian cancer are now available (Gynecologic Oncology Group trial no 111 and the Intergroup trial).1,2 Your June 7 editorial3 makes two inaccurate statements: these studies are not “relatively small” since their combined total is over 1000 patients, and to describe the Intergroup results as preliminary is misleading since it implies that the interpretation may change with further follow-up. This is unlikely because the primary endpoint is progression-free survival and 469 events have occurred (data presented in May, 1997, at the American Society for Clinical Oncology meeting). Response rates and progression-free survival show an impressive advantage for cisplatinpaclitaxel (table). A third study, also presented at ASCO, GOG no 132,4 randomised patients to cisplatin-paclitaxel or singleagent cisplatin or paclitaxel. Response rates to single-agent paclitaxel were significantly lower than those observed in the other two arms, but there was no difference between the three in terms of progression-free or overall survival. This trial has been used to justify not adopting cisplatin-paclitaxel as standard. However, in GOG-132 half the patients crossed over to one of the other treatment groups and this sometimes happened before progression was documented, which calls into question the progression-free survival data. GOG132 is therefore essentially a study of sequential cisplatin-paclitaxel versus first-line treatment with the two drugs combined. It has been difficult to demonstrate an overall survival benefit for individual chemotherapy agents in ovarian cancer because of the relative salvage effect of “crossover” treatment. Advanced Ovarian Cancer Trialists Group5 metaanalysis failed to prove a survival benefit for platinum-based regiments compared with non-platinum-based chemotherapy yet everyone accepts Treatment
platinum as standard. This explains the excitement over GOG-111 and the immediate adoption of the cisplatinpaclitaxel regimen in some quarters. We were unhappy with this change, based on only one trial, and said so at the International Gynaecological Cancer Society in September, 1995. ICON 3 was designed to detect a 10% difference in 2-year survival. 1254 patients have been recruited but with only about 100 events, there is little to analyse. The data monitoring committee has recommended a further 800 patients to allow 4–5% difference in survival to be detected and to permit subset analysis of the two treatments on the main prognostic indicator, the bulk of residual disease after initial surgery. If we assume a range of possible 5-year survivals of 40% down to 15%, a 50% baseline survival at two years (ICON 3 protocol), and statistical power of 90% we calculate that only a 1–2% extra survival benefit can be detected by the addition of 800 patients. The AOCTG overview strongly suggests that carboplatin and cisplatin are of similar efficacy5 (updated by L Stewart in 1997) and there are obvious advantages to carboplatin including reduced neurotoxicity, ototoxicity, and renal toxicity and avoidance of intravenous hydration before and after treatment. Also single-arm carboplatin-paclitaxel dose-escalation phase I/II studies show this to be a well-tolerated regimen. The problem facing ICON 3 investigators is that two good trials already show an impressive advantage in terms of response rates and progression-free survival for cisplatin-paclitaxel over a standard platinum combination regimen. First-line treatment with carboplatin-paclitaxel could therefore be advocated with its low toxicity. ICON 3 is an important trial but crossover treatment may confound the survival data and a further 800 patients are not going to help with the statistical evaluation of any impact on survival. *Martin Gore, Roger A’Hern, Kenneth Swenerton *Royal Marsden Hospital, London SW3 6JJ, UK; and BC Cancer Agency, Vancouver Cancer Centre, BC, Canada
Responses
Progression-free survival
No
%
HR (95% CI)
p
No
Median mo
HR (95% CI)
GOG 111 PC PP
116 100
60 73
Intergroup PC PP
151 149
Overall PC PP
267 249
p
1·76 (1·00–3·09)
<0·05
202 184
13 18
0·7 (0·5–0·8)
<0·001
66 77
1·71 (1·04–2·83)
<0·05
330 338
11 14
0·66 (0·52–0·77)
<0·0001
64 75
1·73 (1·19–2·52)
<0·004
532 522
.. ..
0·68 (0·58–0·79)
<0·000001
PC=cisplatin-cyclophosphamide, PP=cisplatin-paclitaxel, HR=hazard ratio (and 95 % confidence interval).
Response rates and progression-free survival in GOG-111 and Intergroup studies
370
1
2
3
4
5
McGuire WP, Hoskins WJ, Brady MF, et al. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med 1996; 334: 1–6. Piccart MJ, Bertelsen K, Stuart G, et al. Is cisplatin-paclitaxel the standard in first-line treatment of advanced ovarian cancer? The EORTC-GCCG, NOCOVA, NCI-C and Scottish intergroup experience. Proc ASCO 1997; 16: 1258. Editorial. Good manners for the pharmaceutical industry. Lancet 1997; 349: 1635. Muggia FM, Braly PS, Brady MF, et al. Phase III of cisplatin or paclitaxel, versus their combination in suboptimal stage III and IV epithelial ovarian cancer: Gynecologic Oncology Group study 132. Proc ASCO 1997; 16: 1257. Advanced Ovarian Cancer Trialists Group. Chemotherapy in advanced ovarian cancer: an overview of randomised clinical trials. BMJ 1991; 303: 884–93.
SIR—Your June 7 editorial,1 discusses the negative response of Bristol-Myers Squibb to the recommendation by the independent data monitoring committee that the ICON 3 trial should continue. In this trial patients with epithelial ovarian cancer are randomised to receive paclitaxel plus carboplatin or an appropriate platinum control. As one of the larger contributors to the ICON 3 trial, I wish to disagree with the position taken by Bristol-Myers Squibb. The presentation of early data from the Intergroup study2 at the American Society of Clinical Oncology meeting in May, 1997, which confirmed the improvement in progression-free survival study previously shown by the GOG-111 trial3 lends support to the use of paclitaxel in the first-line treatment of patients with epithelial ovarian cancer. However, the publication of data from GOG-1324 at the same meeting demonstrated just how difficult it is to draw conclusions from the results of individual clinical trials. In GOG-132 patients with advanced disease were randomised three ways, and received full-dose single agent cisplatin, paclitaxel 200 mg/m2 given as a 24-h infusion, or a combination of cisplatin and paclitaxel as used previously in GOG-111. Progression-free survival for the two platinum containing arms of the trial was significantly better than in the single agent paclitaxel arm (11·4 months), but there was no difference between single-agent cisplatin and the cisplatin-paclitaxel combination (16·4 and 14·1 months, respectively). There was no difference between the three arms in the survival analysis (paclitaxel 25·9 months, cisplatin 30·2 months, cisplatin-paclitaxel 26·6 months). One of the main differences between GOG132 and both the Intergroup study and GOG-111 is the widespread use of paclitaxel as a salvage treatment. In the UK carboplatin is the most
Vol 350 • August 2, 1997
THE LANCET
widespread standard chemotherapy treatment for ovarian cancer. Previous trials have not been able to show any significant difference in efficiency between single-agent cisplatin and single-agent carboplatin. Carboplatin is of course virtually devoid of the troublesome gastrointestinal and neurotoxicity associated with cisplatin in GOG-132. Within ICON 3, single-agent carboplatin is one of the available control arms and will therefore provide vital data on this comparison. It may indeed turn out that the combination of a platinum drug with paclitaxel is better than standard platinum-based therapy. But if non-responders can be salvaged by the use of paclitaxel later on then this may be a more efficient use of scarce health service resources, particularly since the excess treatment cost of the paclitaxel containing regimen is in the region of £9000. I believe that the ICON 3 trial has to continue in order to provide information that will help to answer these issues. A 2000 patient trial which includes quality-of-life assessment will provide us with extremely valuable and robust information on which we may base our clinical and research decisions for the years to come. It will also provide vital information to those responsible for commissioning health care in the future. Timothy Perren ICRF Cancer Medicine Research Unit, St James’s University Hospital, Leeds LS9 7TF, UK
1
2
3
4
Editorial. Good manners for the pharmaceutical industry. Lancet 1997; 349: 1635. Piccart MJ, Bertelsen K, Stuart G, et al. Is cisplatin-Paclitaxel (P-T) the standard in first-line treatment of advanced ovarian cancer (Ov Ca)? The EORTC-GCCG, NOCOVA, NCI-C and Scottish intergroup experience. Procs Am Soc Clin Oncol 1997; 16: 352a. McGuire WP, Hoskins WJ, Brady MF, et al. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage 111 and stage IV ovarian cancer (see comments). N Engl J Med 1996; 334: 1–6. Muggia FM, Braley PS, Brady MF, et al. Phase 111 of cisplatin (P) or paclitaxel (T), versus their combination in suboptimal stage 111 and IV epithelial ovarian cancer (EOC): Gynecologic Oncology Group. Procs Am Soc Clin Oncol 1997; 16: 352a.
no affect on representatives of the two largest accruing centres as to whether the trial should continue. When we first heard that the Intergroup study had confirmed that patients in the paclitaxel group showed improvement in progression free survival, as previously reported by the Gynaecologic Oncology Group, our initial reaction was that the ICON 3 trial should stop. We wish to explain why we have changed our minds. It is possible that the ICON 3 trial already shows a significant improvement in progression free survival in the paclitaxel group. However, if the improvement in progression free survival of adding paclitaxel in the three trials only amounts to a few months, this may be insufficient benefit to persuade purchasers to provide an extra £9000 for each patient with ovarian cancer. The Intergroup trial has not yet divulged any survival data, and we presume that the data monitoring committee recommended the continuation of ICON 3 because there is not yet a highly significant difference in survival between the paclitaxel group and controls. Unlike the situation in the USA, only a small proportion of our patients who have a relapse are crossing over to paclitaxel, which will allow us to see the effect of paclitaxel on survival. Unless the Intergroup and ICON 3 trials show an improvement in survival sufficient to persuade purchasers to provide more money for cytotoxic chemotherapy, we will not be able to use paclitaxel for NHS patients. It is essential that NHS Regional Research and Development insist that all purchasers fund paclitaxel for this trial, otherwise the trial will stop recruiting UK patients in the UK because of inadequate funding and not because of pressure from Bristol-Myers Squibb. Patients would be the ultimate losers because without reliable data showing whether paclitaxel improves survival, how can they decide whether it is worth losing their hair? *Gordon J S Rustin, Derek Crowther *Centre for Cancer Treatment, Mouth Vernon Hospital, Northwood, Middlesex HA6 2RN, UK; and CRC Department of Medical Oncology, Christie Hospital, Manchester
1
SIR—Your June 7 editorial1 discusses the manners of Bristol-Myers Squibb over the continuation of the third International Collaboration on Ovarian Neoplasm study (ICON 3), in which patients with epithelial ovarian cancer are randomised to receive paclitaxel plus carboplatin or an appropriate platinum control. The media interest inhibited discussion at the open meeting in London on June 2, but had
Vol 350 • August 2, 1997
Editorial. Good manners for the pharmaceutical industry. Lancet 1997; 349: 1635.
SIR—Your June 7 editorial1 justifiably draws attention to the value of large randomised trials of cancer treatment and to the dangers of drawing premature conclusions on new treatments. However, to say that the decision of the Data Monitoring Committee to continue the ICON 3 study to recruit up to 2000 patients should not be debated is unreasonable.
There is a substantial amount of data from randomised trials of paclitaxel in ovarian cancer. As with any series of clinical investigations, many different interpretations are possible. Although arguments in favour of continuing recruitment to ICON 3 can certainly be marshalled, concern over this is understandable because some important points have not, to our knowledge, been clearly answered. What is the statistical probability that the existing randomised studies that show an advantage for paclitaxel are wrong? To what degree was the survival in the cisplatin only group of the GOG132 study affected by second-line treatment with taxanes, and was the serious toxicity observed in this highdose platinum group justifiable? Will the information on these new studies be included in the consent form for patients entering ICON 3? Even the most pessimistic interpretation of the current data still suggests that the overall survival of patients with advanced ovarian cancer is enhanced by the use of paclitaxel given at relapse. Continuation of recruitment to ICON 3 should be conditional on this treatment being available to all patients who are allocated to the control group of this study. *Hilary Calvert, Stan Kaye, Richard Osborne, Karol Sikora, Hilary Thomas *Department of Oncology, University of Newcastle, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE, UK; Department of Medical Oncology, Beatson Institute, University of Glasgow, Glasgow; Dorset Cancer Centre, Poole Hospital Health Trust, Poole; and Department of Clinical Oncology, Royal Postgraduate Medical School, London
1
Editorial. Good manners for the pharmaceutical industry. Lancet 1997; 349: 1635.
Health impact of human rights violations in Haitian refugees SIR—After the 1991 coup in Haiti, extreme oppression by the military resulted in over 40 000 Haitians fleeing the country. During their flight, those intercepted at sea by the US Coast Guard were detained at a naval base in Guantanamo Bay, Cuba. At Guantanamo Bay, the refugees were further exposed to an insecure and unsanitary living environment. Between June, 1992, and October, 1995, we interviewed refugees who had been detained in Guantanamo Bay and were receiving assistance for asylum claims from a legal services agency in the USA. 19 refugees were randomly selected, and 15 (80%)
371