BACKGROUND: Mitomycin C (MMC) produces significant upregulation of thymidine phosphorylase, a principal determinant of the therapeutic index of capecitabine-based treatment, starting 4-6 days after treatment. On the basis of the time-dependency of this upregulation, we performed a phase I dose escalation study of capecitabine and MMC in patients with gastrointestinal malignancies. METHODS: A total of 29 patients with advanced gastrointestinal malignancies received MMC at 6 mg/m2 on day 1 and capecitabine escalated in four successive patient cohorts of doses 500-1,000 mg/m2/day twice daily on days 8-21, every 28 days. MMC was capped at 36 mg/m2. RESULTS: A total of 29 patients were enrolled and 90% had at least one prior treatment in the metastatic setting. There was one DLT, grade 3 hand and foot syndrome, at dose level four. The most common toxicity was fatigue (61%). No patients experienced grade 4 toxicities. Nine patients experienced prolonged stability of disease. CONCLUSION: Capecitabine in combination with MMC in the proposed schedule is well-tolerated with evidence of preliminary activity. The recommended dose for phase II studies are MMC at 6 mg/m2 on day 1 of a 28-day cycle with the dose capped at 36 mg/m2, in combination with capecitabine at 1,000 mg/m2 twice daily on days 8-21.
BACKGROUND:Mitomycin C (MMC) produces significant upregulation of thymidine phosphorylase, a principal determinant of the therapeutic index of capecitabine-based treatment, starting 4-6 days after treatment. On the basis of the time-dependency of this upregulation, we performed a phase I dose escalation study of capecitabine and MMC in patients with gastrointestinal malignancies. METHODS: A total of 29 patients with advanced gastrointestinal malignancies received MMC at 6 mg/m2 on day 1 and capecitabine escalated in four successive patient cohorts of doses 500-1,000 mg/m2/day twice daily on days 8-21, every 28 days. MMC was capped at 36 mg/m2. RESULTS: A total of 29 patients were enrolled and 90% had at least one prior treatment in the metastatic setting. There was one DLT, grade 3 hand and foot syndrome, at dose level four. The most common toxicity was fatigue (61%). No patients experienced grade 4 toxicities. Nine patients experienced prolonged stability of disease. CONCLUSION:Capecitabine in combination with MMC in the proposed schedule is well-tolerated with evidence of preliminary activity. The recommended dose for phase II studies are MMC at 6 mg/m2 on day 1 of a 28-day cycle with the dose capped at 36 mg/m2, in combination with capecitabine at 1,000 mg/m2 twice daily on days 8-21.
Authors: P Therasse; S G Arbuck; E A Eisenhauer; J Wanders; R S Kaplan; L Rubinstein; J Verweij; M Van Glabbeke; A T van Oosterom; M C Christian; S G Gwyther Journal: J Natl Cancer Inst Date: 2000-02-02 Impact factor: 13.506
Authors: Rafael G Amado; Michael Wolf; Marc Peeters; Eric Van Cutsem; Salvatore Siena; Daniel J Freeman; Todd Juan; Robert Sikorski; Sid Suggs; Robert Radinsky; Scott D Patterson; David D Chang Journal: J Clin Oncol Date: 2008-03-03 Impact factor: 44.544
Authors: Paulo M Hoff; Richard Pazdur; Yvonne Lassere; Susan Carter; Dvorit Samid; Diane Polito; James L Abbruzzese Journal: J Clin Oncol Date: 2004-06-01 Impact factor: 44.544
Authors: S Rao; D Cunningham; T Price; M E Hill; P J Ross; N Tebbutt; A R Norman; J Oates; P Shellito Journal: Br J Cancer Date: 2004-08-31 Impact factor: 7.640