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Journal of Clinical Oncology, Vol 23, No 25 (September 1), 2005: pp. 6269-6270 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.01.6659
Is the Tolerance to MIP Chemotherapy Different Between English and Other European Populations?Department of Intensive Care Unit and Thoracic Oncology, Institut Jules Bordet, Brussels, Belgium To the Editor: We read with interest the article published by Rudd et al1 comparing the classical MIP chemotherapy regimen (cisplatin 50 mg/m2, ifosfamide 3 g/m2, mitomycin C 6 mg/m2), as initially described by Cullen et al,2 to the combination of carboplatin and gemcitabine. We are surprised by the number of patients who did not complete the planned four cycles of treatment, representing 36% of the total number of patients included in the MIP arm, though toxicity was moderate. These results are similar to another study previously published by Cullen et al3 in which 38% and 50% of the randomly assigned patients, with respectively localized and extensive diseases, did not receive the planned therapy. Our group, the European Lung Cancer Working Party, has a long experience with the MIP regimen, administered at the same dosage and frequency as in the study of Rudd et al. Three multinational phase III trials were performed by our group.4-6 At the difference of the English trials, the first complete evaluation work-up was planned after three cycles of chemotherapy. Only 13% among 784 patients included in our three trials did not receive the planned first three courses of MIP, compared with 36% in the Rudd et al trial1 who did not complete the planned treatment. Moreover, among patients planned for further chemotherapy according to the design of our randomized trials, only 4% did not complete at least four cycles of MIP. At the difference of Rudd et al, we also had significantly less early cessation for progressive disease (5% v 18%; P < .001) or unacceptable toxicity (3.4% v 8.6%; P = .002). The information available in the Rudd et al publication1 does not allow us explain these differences. Toxicity was moderate, as expected with the MIP regimen, except for 15% grade 4 neutropenia. Only four toxic deaths were documented. We could question the reasons for stopping treatment due to toxicity. Also, patients were assessed for response with minimal work-up such as chest x-ray at the difference of the European Lung Cancer Working Party trials, in which complete work-up with computed tomography scan assessment was performed. This minimal assessment is no longer felt to be standard in the majority of the guidelines. The high rate of early chemotherapy cessation observed in the Rudd et al trial1 and also in the Cullen et al trial3 could be due to some pessimism or minimalism when treating patients with lung cancer, leading to early treatment discontinuation. These considerations might give some explanation about the statistically significant difference observed between the two study arms. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES
1. Rudd RM, Gower NH, Spiro SG, et al: Gemcitabine plus carboplatin versus mitomycin, ifosfamide, and cisplatin in patients with stage IIIB or IV non-small-cell lung cancer: A phase III randomized study of the London Lung Cancer Group. J Clin Oncol 23:142-153, 2005 2. Cullen MH, Joshi R, Chetiyawardana AD, et al: Mitomycin, ifosfamide and cis-platin in non-small cell lung cancer: Treatment good enough to compare. Br J Cancer 58:359-361, 1988[Medline]
3. Cullen MH, Billingham LJ, Woodroffe CM, et al: Mitomycin, ifosfamide, and cisplatin in unresectable non-small-cell lung cancer: Effects on survival and quality of life. J Clin Oncol 17:3188-3194, 1999
4. Sculier JP, Paesmans M, Lafitte JJ, et al: A randomised phase III trial comparing consolidation treatment with further chemotherapy to chest irradiation in patients with initially unresectable locoregional non-small-cell lung cancer responding to induction chemotherapy: European Lung Cancer Working Party. Ann Oncol 10:295-303, 1999 5. Sculier JP, Lafitte JJ, Paesmans M, et al: Phase III randomized trial comparing moderate-dose cisplatin to combined cisplatin and carboplatin in addition to mitomycin and ifosfamide in patients with stage IV non-small-cell lung cancer. Br J Cancer 83:1128-1135, 2000[CrossRef][Medline]
6. Sculier JP, Lafitte JJ, Berghmans T, et al: A phase III randomised study comparing two different dose-intensity regimens as induction chemotherapy followed by thoracic irradiation in patients with advanced locoregional non-small-cell lung cancer. Ann Oncol 15:399-409, 2004
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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