Pegylated liposomal doxorubicin, 5-fluorouracil and cisplatin versus mitomycin-C, 5-fluorouracil and cisplatin for advanced gastric cancer: A randomised phase II trial

Abstract

13521 Background: In the treatment of gastric cancer a debated question is represented by the role of anthracyclines. In fact, in spite of the results obtained by ECF and the Cochrane’s metanalysis results, there is no general agreement on the contribution of anthracyclines to cisplatin and 5-fluorouracil (5FU). The development of alternative formulations of anthracyclines, such as pegylated liposomal doxorubicin with lower inherent toxicity may improve tolerability and efficacy of anthracycline based regimens. Based on these considerations, a combination of pegylated liposomal doxorubicin, 5FU and cisplatin was evaluated and compared with mitomycin-C and 5FU and cisplatin which served as internal control arm to avoid selection bias. Methods: Patients with locally advanced and/or metastatic gastric cancer were randomly assigned to receive: 5FU 400 mg/m2 bolus, followed by 600 mg/m2, 22h continuous infusion day and 2 and cisplatin 50 mg/m2 day 1 every two weeks combined with pegylated liposomal doxorubicin 20 mg/m2 day 1 every two weeks or mitomycinC 7 mg/m2 every 6 weeks. Results: Seventy-eight patients were randomly assigned. Toxicity was rarely severe. Major toxic effects included leukopenia and cutaneous toxicity, 305 and 25% of patients, respectively in liposomal doxorubicin arm, and leukopenia and thrombocytopenia (35% and 33%, respectively) in mitomycin-C arm. Activity and efficacy are summarised in table 1. Conclusions: Liposomal doxorubicin in combination with 5FU and cisplatin shows promising efficacy compared with a three-drug regimen commonly used in our group. The three-drug regimen including liposomal doxorubicin could be compared with the TCF regimen and may represent a treatment option for the treatment of advanced gastric cancer. Liposomal Doxorubicin Mitomycin-C Evaluable patients 39 39 CR 5 4 PR 17 11 SD 10 13 PD 7 11 PFD (median, months) (HR 0.62, 95%CI, 0.37–0.97, p= 0.04) 7.93 5.14 OS (median, months) (HR, 0.59. 95% CI, 0.34–0.94, p=0.02) 12.1 8.3 No significant financial relationships to disclose.