A phase II evaluation of tirapazamine plus cisplatin in the treatment of recurrent platinum-sensitive ovarian or primary peritoneal cancer: a Gynecologic Oncology Group study

OBJECTIVES: To estimate the anti-tumor activity, nature and degree of toxicity of tirapazamine in combination with cisplatin in patients with recurrent platinum-sensitive ovarian or primary peritoneal cancers. METHODS: Eligible consenting patients had to have recurrent epithelial ovarian or primary peritoneal carcinoma with measurable disease. Patients were not allowed to have received any additional cytotoxic chemotherapy for management of recurrent or persistent disease, including re-treatment with initial chemotherapy regimens. Patients must have been platinum-sensitive, meaning a treatment-free interval of >6 months after response to a platinum-based regimen. The RECIST criteria were used for parameters of response. Tirapazamine was administered at a dose of 390 mg/m2 IV over 2 h followed 1 h later by cisplatin 60 mg/m2 IV every 3 weeks until disease progression or adverse effects prohibited further therapy. RESULTS.: Between June 2001 and February 2004, 65 patients were entered onto this study by 27 institutions; one patient was excluded due to ineligible tumor type. Twenty-six patients (41%) received six or more cycles of therapy; however, 16 (25%) received one course of therapy (mainly due to side effects or patient request). There were six (9%) complete responders and 28 (44%) partial responders for a total response rate of 53%. Only two patients (3%) developed increasing disease on this protocol, and response could not be assessed in 18 patients (28%). The median progression-free and overall survival for all patients is 10.9 and 26.4 months, respectively. The regimen did not cause major hematologic toxicity, however, it did cause frequent constitutional (23%) and gastrointestinal (mostly nausea/vomiting) (44%) grade 3 or 4 toxicity. CONCLUSIONS: The combination of tirapazamine and cisplatin has definite activity in the treatment of recurrent platinum-sensitive ovarian or primary peritoneal cancer. However, toxicity, primarily non-hematologic, was substantial. Reducing the toxicity of a tirapazamine-platinum combination should be pursued in future trials.