Phase II Trial of CI-980 in Patients with Disseminated Malignant Melanoma and no Prior Chemotherapy – A Southwest Oncology Group Study

Abstract

Malignant melanoma is increasing infrequency at a rapid rate in the UnitedStates. Metastatic disease ischemoresistant with DTIC considered themost active single agent. CI-980 is asynthetic mitotic inhibitor that blocks theassembly of tubulin and microtubules. Ithas shown cytotoxic activity against abroad spectrum of murine and human tumorcell tines. CI-980 can cross the bloodbrain barrier, is effective when givenorally or parenterally, and is activeagainst multidrug resistant cell linesoverexpressing P-glycoprotein. In thistrial, patients with disseminated melanomawith measurable disease, SWOG performancestatus of 0–1, no prior chemotherapy orimmunotherapy for metastatic disease, andadequate hepatic and renal function, wereenrolled. Treatment with CI-980 was givenby 72 h continuous IV infusion at a doseof 4.5 mg/m 2 /day, days 1–3 every 21 days. Twenty-four patients were registered onthis study with no patients ineligible. They ranged in age from 33–78 withperformance status of 0 in 15 patients and1 in 9 patients. Nineteen patients hadvisceral disease with 12 having liverinvolvement. There were no confirmedresponses. The overall response rate was0% (95% CI 0%–14%). The medianoverall survival is eleven months (95% CI4–14 months). The most common toxicitieswere hematologic and consisted ofleukopenia/granulocytopenia and anemia,with nausea/vomiting andmalaise/fatigue/weakness also frequent. CI-980 administered at this dose andschedule has insufficient activity in thetreatment of disseminated malignantmelanoma to warrant furtherinvestigation.