Evaluation of oxaliplatin dose intensity in bimonthly leucovorin and 48-hour 5-fluorouracil continuous infusion regimens (FOLFOX) in pretreated metastatic colorectal cancer |
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Authors: | F Maindrault-Goebel A de Gramont C Louvet T André E Carola V Gilles J P Lotz C Tournigand M Mabro J L Molitor P Artru V Izrael M Krulik |
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Affiliation: | (1) Service de Médecine Interne-Oncologie, Hôpital Saint-Antoine, Paris, France;(2) Service d'Oncologie Médicale, Hôpital Tenon, Paris, France;(3) Service de Médecine 2, Hôpital de Senlis, Senlis, France |
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Abstract: | Background:studies of bimonthly 48-hour regimens of high-doseleucovorin (LV) (FOLinic acid), 5-fluorouracil (5-FU) by continuous infusioncombined with OXaliplatin (FOLFOX) in pretreated patients with metastaticcolorectal cancer suggest that oxaliplatin dose intensity is an importantprognostic factor for response rate and progression-free survival (PFS). Tohelp define the optimal dose schedule for oxaliplatin in pretreated metastaticcolorectal cancer, we retrospectively analyzed data from three phase IIstudies using different FOLFOX regimens (FOLFOX2, 3 and 6).Patients and methods:Data on 126/161 patients were analyzed.FOLFOX2 included oxaliplatin 100 mg/m2; FOLFOX3, 85mg/m2; and FOLFOX6, 100 mg/m2 (added to a simplifiedLV–5-FU regimen), all as two-hour infusions. A total of 47 patientsreceived low dose intensity oxaliplatin (LDI: 85 mg/m2/2 weeks)and 79 patients high dose intensity oxaliplatin (HDI: >85mg/m2/2 weeks).Results:Objective responses occurred in 31 (39%) HDIpatients and 9 (19%) LDI patients (P = 0.03). Median PFS was28 weeks, with 52% of HDI patients progression free at 6 months, and26 weeks with 36% of LDI patients progression free at six months(P = 0.02). Increased oxaliplatin dose intensity was not associatedwith increased neurotoxicity or other toxicities. FOLFOX are among the mosteffective regimens for treating LV–5-FU-resistant metastatic colorectalcancer.Conclusions:This study shows that oxaliplatin doseintensification significantly improves response rate and PFS in pretreatedmetastatic disease without increasing severe toxicity. |
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Keywords: | advanced colorectal carcinoma dose intensity 5-fluorouracil FOLFOX leucovorin oxaliplatin |
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