[Combination of irinotecan hydrochloride (CPT-11) and cisplatin as a new regimen for patients with advanced ovarian cancer].

Abstract

It has been reported that the antitumor effect of CPT-11 is manifested through the inhibition of topoisomerase I by SN-38 which is an active metabolite of CPT-11 produced by intracellular carboxylesterase, and that CPT-11 is effective against recurrent ovarian carcinoma. We investigated the antitumor effect and adverse reactions in the combined therapy with CPT-11 and CDDP in patients with prior chemotherapy for recurrent carcinoma, and in 7 patients without prior chemotherapy, consisting of 4 patients with postoperative adjuvant chemotherapy for clear cell carcinoma and 3 patients with metastatic ovarian carcinoma. CDDP was administered on day 1 and CPT-11 was administered three times on days 1, 8 and 15. The dose of both CDDP and CPT-11 was 50 mg/m2 or 60 mg/m2. Adverse reactions were investigated in all patients and the antitumor effect was assessed in 12 patients with recurrent carcinoma who had measurable lesions. (1) The DLF was neutropenia. The neutrophil count nadiar occurred on day 18 or 19. Grade 3 or 4 adverse reactions were observed in 60% or more of the patients, but they disappeared following short term administration of G-CSF. In patients with recurrent carcinoma given CDDP and CPT-11 at 60 mg/m2, the incidence of grade 3 or 4 adverse reactions and number of occasions on which CPT-11 administration had to be postponed were higher than those in patients given 50 mg/m2. (2) Mild platelet reduction was observed. (3) Grade 3 or 4 diarrhea was observed in 3.2% of patients with recurrent carcinoma and in 7.7% of patients with metastatic ovarian carcinoma. (4) The antitumor effect was evaluated in 12 patients with recurrent carcinoma: CR in 2 patients. PR in 3, NC in 6, and PD in one. The response rate was 41.7%. (5) An antitumor effect was observed in 2 patients with serous carcinoma and in one patient each with mucous carcinoma, clear cell carcinoma and endometrial carcinoma. In conclusion, adverse reactions caused by the combination therapy with CPT-11 and CDDP (CPT-11: 50-60 mg/m2 on days 1, 8 and 15, CDDP: 50-60 mg/m2 on day 1) can be relieved by short term administration of G-CSF and it is suggested that the combination therapy may be effective in treating ovarian carcinoma.