Intraperitoneal high-dose cisplatin and etoposide with systemic thiosulfate protection in second-line treatment of advanced ovarian cancer.
Several randomized trials of various malignancies treated with cisplatin indicate a dose-response relationship with higher MST and longer survival achieved with high-dose compared to standard dose cisplatin regimens. Thirty-five patients with stages II-IV ovarian cancer with refractory cancer at second look or recurrent disease were treated second line with intraperitoneal (ip) combination chemotherapy of high-dose cisplatin (100-200 mg/m2) plus etoposide (350 mg/m2) in 1-6 cycles. Sodium thiosulfate was given as an intravenous antidote to cisplatin. A WBC nadir < 2.0 x 10(9)/liter was registered in 39 courses and a platelet nadir < 50 x 10(9)/liter in 3 courses. Severe nephrotoxicity was observed in 2 patients. Nonhematologic and nonrenal toxicity was mild except for vomiting and nausea and alopecia. No severe neurotoxicity was observed. A total of 127 courses were administered. Total median administered dose was 960 mg and 49 mg/m2/week. Treatment was changed in 5 (14%) patients due to severe nausea and vomiting, in 4 (11%) patients due to PAC problems, and in 2 (6%) patients due to nephrotoxicity. In 4 (11%) patients the dose was reduced due to hematologic toxicity. No toxic death was recorded. Median survival time from date of diagnosis was 21.8 (mean 37.9) months and the median progression-free survival from start of ip chemotherapy was 13.7 months. For patients with MRD < or = 2 cm the MST was 18.1 months. At the closing point of this study after a median follow-up time of 16.1 (range, 4.6-55.6) months, 7 (20%) patients were alive without evidence of progression, 4 (11%) were alive with cancer, and 23 (66%) were dead of cancer and 1 (3%) was dead of intercurrent disease.
Department of Gynecologic Oncology, University Hospital, Linköping, Sweden.
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H
Malmström
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S
Rasmussen
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E
Simonsen
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate; D013885:Thiosulfates / Q000008:administration & dosage*
D013885:Thiosulfates; D005047:Etoposide; C017717:sodium thiosulfate; D002945:Cisplatin