Combination therapy with S-1 and irinotecan (CPT-11) for advanced or recurrent gastric cancer
Tóm tắt
S-1 and irinotecan (CPT-11) are active agents against gastric cancer. Some preclinical studies have demonstrated the theoretical background of combination therapy with S-1 and CPT-11 for gastric cancer. Based on these findings, several phase I/II studies of this combination therapy, which has been proposed as a candidate of standard treatment for advanced or recurrent gastric cancer in Japan, have been conducted. Although there were slight differences in the administration schedules of the combination therapy with S-1 and CPT-11 in these phase II studies, the response rates were more than 50%, and the median survival time (MST) exceeded 1 year. Also, good safety profiles were reported. These results warranted a further, phase III, study to define the efficacy of the combination in improving survival. In a phase III study (GC0301/TOP 002 trial), the response rate, the 1-year survival rate, and the MST in the arm with combination therapy of S-1 and CPT-11 were better than these parameters in the S-1 monotherapy arm. However, at 1.5-year follow-up, the overall survival (OS) in the combination therapy of S-1 and CPT-11 arm did not exceed that in the S-1 monotherapy arm [P = 0.23; hazard ratio (HR), 0.89]. As 22% of the patients were censored, further follow-up is needed to determine the OS with more precision. But, of note, in the SPIRITS trial, combination therapy with S-1 and cisplatin (CDDP) significantly prolonged OS compared to S-1 monotherapy (P = 0.037; HR, 0.77), suggesting that CPT-11 may not be the best partner to use in combination with S-1 at present.
Tài liệu tham khảo
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