A Phase II Trial of JM-216 in Cervical Cancer: An NCIC CTG Study

OBJECTIVE: BMS-182751 (JM-216) is an orally bioavailable platinum compound with activity in platinum-sensitive and platinum-resistant preclinical models. The objective was to determine its activity in recurrent/metastatic squamous cell carcinoma of the cervix. METHODS: We conducted a phase II study of BMS-182751 given at a dose of 30 mg/m(2) daily for 14 days every 5 weeks. RESULTS: Eighteen patients (pts) with advanced/recurrent squamous cancer of the cervix not amenable to curative therapy with measurable disease who had received no prior chemotherapy for systemic disease were entered, all of whom are evaluable for response and toxicity. Median age was 47 years (35-74 years); all pts had received prior pelvic irradiation (RT); 4 pts had received cisplatin as adjustment therapy with radiation; PS was 0 (6 pts), 1 (7 pts), and 2 (5 pts); sites of disease included nodes (10 pts), pelvis (5 pts), lung (4 pts), and bone (3 pts). Median number of cycles was two (1-6) with 8 pts receiving three or more cycles. Toxicity was modest and usually grade 1 or 2 in severity with the most frequent drug related toxicity being nausea (56%), fatigue (50%), anorexia (39%), diarrhea (39%), vomiting (39%), constipation (28%), and altered taste (22%). Six pts had grade 3 or 4 granulocytopenia and only 1 pt, grade 3 or 4 thrombocytopenia. Two pts had grade 2 or 3 creatinine increases. There were no treatment-related deaths. One pt with a treatment-free interval of 30 years achieved a partial response, while 12 pts had a best response of stable disease. CONCLUSIONS: BMS-182751 is generally well tolerated, but has limited activity in pts with recurrent cervical cancer.