Activity and safety of a low dose, fractional administration of irinotecan hydrochloride (CPT-11) in combination with cisplatin for relapsed gastric cancer patients: a preliminary report

Abstract.

Background: Irinotecan hydrochloride (CPT-11) in combination with cisplatin has emerged as a new therapeutic option for the treatment of advanced gastric cancer. So far, very few combination trials have been reported, and a relatively high frequency of grade 3/4 toxicities in previous trials has been a major problem. The purpose of this study was to elucidate the efficacy and safety of a low dose, fractional administration of CPT-11 and cisplatin that is principally based on recently acquired knowledge of the synergistic antitumor activities between these two agents.

Methods: Five relapsed gastric cancer patients were treated every 2 weeks with a starting dose of CPT-11 (30 mg/m²) and a fixed dose of cisplatin (30 mg/m²). All patients were of performance status 0 and had received prior chemotherapy. Dose escalation of CPT-11 to 40 mg/m² or to 50 mg/m² was performed whenever possible. Responses, toxicities, and at-home ratio during chemotherapy were evaluated.

Results: The response rate reached 40%. Toxicities were grade 1/2, and no grade 3/4 hematological toxicities or diarrhea were observed. Repeated subsequent treatments could be performed in an outpatient setting without treatment delay or cancellations, which resulted in an 83%–92% at-home ratio in four patients receiving five or more cycles of treatment. There were no treatment-related deaths.

Conclusion: A low dose, fractional administration of CPT-11 and cisplatin seems rational, encouraging, and safe, and compares well with other trials of the combination. Outpatient administration provides the patients with a better quality of life, suggesting a meaningful therapeutic option for relapsed gastric cancer patients in particular.