- Email: [email protected]
Dose-dense paclitaxel for advanced ovarian cancer
Correspondence
pathic remedy, which is only vigorously shaken water, costs €175 per L) whereas the vast majority of primary care trusts in the UK have cut funding. In 2007, the French medicine agency (Afssaps) issued a national official warning to pharmacists and doctors after a mix-up in the labelling of two homoeopathic remedies by the company.2 However, the preparations only differed in terms of the vial’s label! Placebos lack objective clinical effects: if you secretly slip a placebo into a person’s drink, it doesn’t work. Placebos are marketed by moneyhungry quacks, they strengthen medical arrogance and infantilise patients. This has a name: disease mongering.3 Neither drug-regulatory authorities, nor scientific committees, must support this prolonged mess. I declare that I have no conflicts of interest.
Alain Braillon [email protected] Department of Public Health, University Hospitals, 80000 Amiens, France 1
2
3
Garattini S, Bertelé V. Homoeopathy: not a matter for drug-regulatory authorities. Lancet 2009; 374: 1579–80. DC’s Improbable Science. Attention mes amis! Homeopathic emergency in France! http:// www.dcscience.net/?p=196 (accessed Jan 6, 2009). Braillon A. Placebo is far from benign: it is disease-mongering. Am J Bioeth 2009; 9: 52–54.
In this trial, less than half the women achieved an optimum level of residual disease. Currently reported rates of cytoreduction2 and chemotherapy feasibility are generally higher.2,3 Previous analyses of randomised trials have suggested that women with macroscopic residual disease are the ones that benefit most from aggressive chemotherapy schedules.4 Additionally, in the control group, 27% of women were unable to receive standard chemotherapy owing to toxic effects. This is likely to have had a detrimental role in their prognosis. If this hypothesis holds true, the benefits seen in the study group could reflect impaired prognosis in the control group, and high-dose paclitaxel may have compensated for a low platinum dose. An analysis of women who received six or more cycles would allow us to draw more generalisable conclusions. Weekly regimens in ovarian cancer treatment are yielding important results with favourable toxicity profiles. Results from ongoing trials5 will show whether such schedules really need to be dose-intense. We declare that we have no conflicts of interest.
Filippo Bellati, *Marco Calcagno, Pierluigi Benedetti Panici [email protected] Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Rome “Sapienza”, 00161 Rome, Italy 1
Dose-dense paclitaxel for advanced ovarian cancer Science Photo Library
The results of the JGOG trial in ovarian cancer (Oct 17, p 1331)1 show a significant benefit in terms of progression-free survival in the group on adjuvant weekly high-dose paclitaxel. Such improvements are in the magnitude of those achieved by the introduction of platinum compounds. However, some features of the JGOG study should be highlighted. 280
2
3
4 5
Katsumata N, Yasuda M, Takahashi F, et al. Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, openlabel, randomised controlled trial. Lancet 2009; 374: 1331–38. Bookman MA, Brady MF, McGuire WP, et al. Evaluation of new platinum-based treatment regimens in advanced-stage ovarian cancer: a phase III trial of the Gynecologic Cancer Intergroup. J Clin Oncol 2009; 27: 1419–25. Ozols RF, Bundy BN, Greer BE. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol 2003; 21: 3194–200. Earl H. ICON3 and chemotherapy for ovarian cancer. Lancet 2002; 360: 2087. Bookman MA. Dose-dense chemotherapy in advanced ovarian cancer. Lancet 2009; 374: 1303–05.
Noriyuki Katsumata and colleagues1 report that dose-dense weekly paclitaxel plus carboplatin improves survival compared with the conventional regimen in patients with advanced ovarian cancer. This study presents a new treatment option for women with advanced disease. As is known, a reduction in CA-125 antigen concentration is regarded as evidence of response to treatment in ovarian cancer.2 Some studies have suggested that a 50% or 75% reduction in CA-125 concentration could be accepted as measurements of response and could be used in addition to or in place of criteria set out by WHO, the Eastern Cooperative Oncology Group, or the Gynecologic Oncology Group for patients receiving initial chemotherapy.3,4 So we suggest that Katsumata and colleagues could add CA-125 antigen concentration to the baseline characteristics; thus, through the Cox’s proportional hazards model, much more information would be obtained. Another issue is why Katsumata and colleagues did not use RECIST (response evaluation criteria in solid tumours) as response criteria.5 The WHO criteria sometimes lead to confusion in interpretation of trial results since they are often “modified” to accommodate new technologies or to address areas that were unclear in the original document. RECIST uses unidimensional, rather than bidimensional (as in the WHO criteria), measures of overall evaluation of tumour burden. The RECIST criteria have subsequently been widely adopted by academic institutions and cooperative groups for trials in which the primary endpoints are objective response or progression. We declare that we have no conflicts of interest.
*Yue-Can Zeng, Rong Wu, Zhao-Guo Xu, Feng Chi [email protected] Department of Medical Oncology, Shengjing Hospital of China Medical University, Shenyang 110004, China
www.thelancet.com Vol 375 January 23, 2010
pathic remedy, which is only vigorously shaken water, costs €175 per L) whereas the vast majority of primary care trusts in the UK have cut funding. In 2007, the French medicine agency (Afssaps) issued a national official warning to pharmacists and doctors after a mix-up in the labelling of two homoeopathic remedies by the company.2 However, the preparations only differed in terms of the vial’s label! Placebos lack objective clinical effects: if you secretly slip a placebo into a person’s drink, it doesn’t work. Placebos are marketed by moneyhungry quacks, they strengthen medical arrogance and infantilise patients. This has a name: disease mongering.3 Neither drug-regulatory authorities, nor scientific committees, must support this prolonged mess. I declare that I have no conflicts of interest.
Alain Braillon [email protected] Department of Public Health, University Hospitals, 80000 Amiens, France 1
2
3
Garattini S, Bertelé V. Homoeopathy: not a matter for drug-regulatory authorities. Lancet 2009; 374: 1579–80. DC’s Improbable Science. Attention mes amis! Homeopathic emergency in France! http:// www.dcscience.net/?p=196 (accessed Jan 6, 2009). Braillon A. Placebo is far from benign: it is disease-mongering. Am J Bioeth 2009; 9: 52–54.
In this trial, less than half the women achieved an optimum level of residual disease. Currently reported rates of cytoreduction2 and chemotherapy feasibility are generally higher.2,3 Previous analyses of randomised trials have suggested that women with macroscopic residual disease are the ones that benefit most from aggressive chemotherapy schedules.4 Additionally, in the control group, 27% of women were unable to receive standard chemotherapy owing to toxic effects. This is likely to have had a detrimental role in their prognosis. If this hypothesis holds true, the benefits seen in the study group could reflect impaired prognosis in the control group, and high-dose paclitaxel may have compensated for a low platinum dose. An analysis of women who received six or more cycles would allow us to draw more generalisable conclusions. Weekly regimens in ovarian cancer treatment are yielding important results with favourable toxicity profiles. Results from ongoing trials5 will show whether such schedules really need to be dose-intense. We declare that we have no conflicts of interest.
Filippo Bellati, *Marco Calcagno, Pierluigi Benedetti Panici [email protected] Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Rome “Sapienza”, 00161 Rome, Italy 1
Dose-dense paclitaxel for advanced ovarian cancer Science Photo Library
The results of the JGOG trial in ovarian cancer (Oct 17, p 1331)1 show a significant benefit in terms of progression-free survival in the group on adjuvant weekly high-dose paclitaxel. Such improvements are in the magnitude of those achieved by the introduction of platinum compounds. However, some features of the JGOG study should be highlighted. 280
2
3
4 5
Katsumata N, Yasuda M, Takahashi F, et al. Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, openlabel, randomised controlled trial. Lancet 2009; 374: 1331–38. Bookman MA, Brady MF, McGuire WP, et al. Evaluation of new platinum-based treatment regimens in advanced-stage ovarian cancer: a phase III trial of the Gynecologic Cancer Intergroup. J Clin Oncol 2009; 27: 1419–25. Ozols RF, Bundy BN, Greer BE. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol 2003; 21: 3194–200. Earl H. ICON3 and chemotherapy for ovarian cancer. Lancet 2002; 360: 2087. Bookman MA. Dose-dense chemotherapy in advanced ovarian cancer. Lancet 2009; 374: 1303–05.
Noriyuki Katsumata and colleagues1 report that dose-dense weekly paclitaxel plus carboplatin improves survival compared with the conventional regimen in patients with advanced ovarian cancer. This study presents a new treatment option for women with advanced disease. As is known, a reduction in CA-125 antigen concentration is regarded as evidence of response to treatment in ovarian cancer.2 Some studies have suggested that a 50% or 75% reduction in CA-125 concentration could be accepted as measurements of response and could be used in addition to or in place of criteria set out by WHO, the Eastern Cooperative Oncology Group, or the Gynecologic Oncology Group for patients receiving initial chemotherapy.3,4 So we suggest that Katsumata and colleagues could add CA-125 antigen concentration to the baseline characteristics; thus, through the Cox’s proportional hazards model, much more information would be obtained. Another issue is why Katsumata and colleagues did not use RECIST (response evaluation criteria in solid tumours) as response criteria.5 The WHO criteria sometimes lead to confusion in interpretation of trial results since they are often “modified” to accommodate new technologies or to address areas that were unclear in the original document. RECIST uses unidimensional, rather than bidimensional (as in the WHO criteria), measures of overall evaluation of tumour burden. The RECIST criteria have subsequently been widely adopted by academic institutions and cooperative groups for trials in which the primary endpoints are objective response or progression. We declare that we have no conflicts of interest.
*Yue-Can Zeng, Rong Wu, Zhao-Guo Xu, Feng Chi [email protected] Department of Medical Oncology, Shengjing Hospital of China Medical University, Shenyang 110004, China
www.thelancet.com Vol 375 January 23, 2010