Intraperitoneal versus intravenous cisplatin in combination with intravenous cyclophosphamide and epidoxorubicin in optimally cytoreduced advanced epithelial ovarian cancer: A randomized trial of the Gruppo Oncologico Noud-Ovest

Intraperitoneal chemotherapy has a strong biological and pharmacological rationale in the treatment of ovarian cancer. From 1989 to 1996 the present study included 113 patients with FIGO stage II-IV ovarian cancer with residual disease less than 2 cm who were randomly allocated to receive 50 mg/m(2) intraperitoneal cisplatin (CDDP) plus 60 mg/m(2) intravenous epidoxorubicin (EPIDOX) and 600 mg/m(2) intravenous cyclophosphamide (CTX) (ipPEC arm) or 50 mg/m(2) intravenous CDDP plus 60 mg/m(2) intravenous EPIDOX and 600 mg/m(2) intravenous CTX (ivPEC arm). Chemotherapy was repeated every 4 weeks for six cycles. Treatment protocol was changed in 22 patients, 2 from the iv arm (who received single-agent carboplatin) and 20 from the ip arm (who were crossed to systemic chemotherapy, ivPEC, or single-agent carboplatin). At the end of chemotherapy, a second-look was performed in 33 of the 54 patients from the ip arm and in 34 of the 57 patients from the systemic arm. The pathologic complete response rate was 41% of all entered patients and 69% of patients submitted to second-look. No significant difference in pathologic response rate as well as in hematologic and nonhematologic toxicities was seen between the two arms. Up to September 1998, 72 patients showed a disease recurrence (33 treated with ipPEC and 39 treated with ivPEC), 55 died (22 ipPEC and 30 ivPEC), and 10 were lost to follow-up (6 ipPEC and 4 ivPEC). Median progression-free survival was 42 and 25 months for ipPEC and ivPEC, respectively (p = 0.13). Median overall survival was 67 and 51 months for ipPEC and ivPEC, respectively (p = 0.14). In conclusion, besides confirming that intraperitoneal chemotherapy is feasible with acceptable toxicity but with poor compliance in community hospitals, this trial showed that intraperitoneal CDDP compared with intravenous CDDP in combination with EPIDOX and CTX obtained a slight (not significant) improvement in progression-free survival and overall survival of optimally cytoreduced advanced ovarian cancer patients. (C) 2000 Academic Press.