Phase I study of paclitaxel plus irinotecan combination therapy for patients with refractory and advanced gastric cancer

Summary

Background

No adequate second-line chemotherapy regimen for advanced gastric cancer is available.

Aims

To determine the safety and optimal dose of paclitaxel/irinotecan as a second-line chemotherapy for patients with advanced and recurrent gastric cancer.

Patients and methods

Sixteen patients with refractory and advanced measurable gastric cancer who were resistant to 5-FU plus cis-diamminedichloroplatinum (CDDP) therapy (FP) were enrolled. Paclitaxel/irinotecan was given intravenously on days 1, 8, and 15 in repeated 4-week cycles. Paclitaxel/irinotecan doses were escalated in a stepwise fashion as follows: 50/40 mg/m², 50/50 mg/m², 50/60 mg/m², 60/60 mg/m², 60/70 mg/m² in levels I, II, III, IV and V, respectively.

Results

Because of one patient with Grade 3 febrile neutropenia at level I, three more patients were enrolled in level I. Doses were consequently escalated, and in level IV, Grade 3 febrile neutropenia occurred in one patient. Since an additional patient in level IV had grade 4 neutropenia, Level IV was judged as the maximum tolerated dose (MTD). The recommended dose and schedule for phase II study is paclitaxel 50 mg/m² and irinotecan 60 mg/m² on days 1, 8, and 15 every 4 weeks. Partial response was observed in 4 of 16 patients.

Conclusion

Paclitaxel/irinotecan combination regimen at the level III dosage was safe and well tolerated.