Mitomycin C, 5-Fluorouracil, Leucovorin, and Oxaliplatin as a Salvage Therapy for Patients with Cisplatin-Resistant Advanced Gastric Cancer: A Phase I Dose Escalation Trial

Abstract

This study aimed at evaluating the feasibilityand toxicity of a salvage therapy with mitomycin C(MMC), 5-fluorouracil (5-FU), leucovorin, and oxaliplatinin patients with cisplatin-resistant advanced gastric cancer.Methods: A 3-patient cohort dose-escalating studydesign was used. The patients received FLO: oxaliplatin85 mg/m2, 5-FU 2,600 mg/m2 (24 h), leucovorin 200mg/m2 on days 1, 15, and 29 plus MMC on day 1 (FLOM).The MMC dose was escalated from 6 to 12 mg/m2 in 2-mg/m2 steps. Cycles were repeated every 6 weeks. Results:Twenty patients were enrolled in 4 treatment cohorts.The treatment was well tolerated with grade 3 or 4nonhematological toxicities affecting less than 5% of patients.Grade 3 or 4 neutropenia, anemia, and thrombocytopeniawere observed in 9 (45%), 7 (35%), and 5 (25%)of 20 patients, respectively. Mild but prolonged thrombocytopeniawas dose limiting, requiring treatment discontinuationor a treatment delay =2 weeks in 8 (40%) of20 patients. MMC 10 mg/m2 every 6 weeks was consideredas the optimal dose in combination with FLO. Objectiveresponses were observed in 7 (35%) of 20 patients,and 7 further patients (35%) had stable disease. Mediantime to progression and overall survival were 4.1 and 8months, respectively. Conclusions: Prolonged cumulativemyelotoxicity was dose limiting in the therapy withMMC, 5-FU, and oxaliplatin. This combination chemotherapyseems to overcome cisplatin resistance in patientswith advanced gastric cancer.