EVALUATION OF MERBARONE (NSC-336628) IN DISSEMINATED MALIGNANT-MELANOMA - A SOUTHWEST-ONCOLOGY-GROUP STUDY

Merbarone, NSC 336628, is an investigational anticancer drug with acti vity against experimental animal tumors including melanoma. This paper presents results of a Phase II clinical study of merbarone in patient s with biopsy proven stage IV malignant melanoma without prior chemoth erapy and with no evidence of CNS involvement. Thirty-five patients wi th median age 58 (range 27-81), with performance status 0-2 were treat ed with merbarone 1000 mg/m(2)/day for five days by intravenous contin uous infusion repeated every 3 weeks. All patients (21 males and 14 fe males) were evaluable for toxicity. Two patients were not evaluable fo r response having been removed from protocol treatment due to toxicity and received other treatment during the first course of chemotherapy. Among the evaluable patients there was one complete response in a sup raclavicular lymph node lasting four months and one partial liver resp onse lasting three months. The remaining thirty-one patients were non- reponders. Of these one had a stable disease lasting 21 months. The ov erall objective response rate was 6% (2/35) with a 95% confidence inte rval of 1%-19%. Twenty-six of the 35 patients have died. The estimated median survival of the entire group was 9 months with a 95% confidenc e interval of six to eleven months. Renal toxicity was dose-limiting a nd manifested as increasing serum creatinine (54% of patients), protei nuria (51%) and hematuria (9%). One patient experienced grade 4 creati nine increase, proteinuria and acute renal failure. Other toxicities i ncluded nausea (71%), vomiting (51%), malaise (23%), weakness (20%), a lopecia (17%), diarrhea (17%), anorexia (14%), transaminase (SCOT, SGP T) increase (14%), constipation (14%), alkaline phosphatase or 5'nucle otidase increase (9%), and fever (9%). Hematologic toxicity (granulocy topenia, leukopenia, and anemia) was generally mild and infrequent (29 %, only one patient had grade 4 granulocytopenia). Overall 9 patients (26%) had at least one grade 3 toxicity. We conclude that merbarone at this dose and schedule has detectable but minimal activity in the tre atment of metastatic malignant melanoma and given the significant rena l toxicity this schedule does not merit further evaluation in this dis ease.