PHASE-II CLINICAL-TRIALS WITH RHIZOXIN IN BREAST-CANCER AND MELANOMA

Rhizoxin is a new anti-tumour agent isolated from the pathogenic fungu s Rhizopus chinensis. It has shown broad activity against murine tumou r models and is also active against vinca alkaloid-resistant cells. Th e purpose of our studies was to determine the clinical activity of thi s compound in patients with advanced breast cancer and melanoma. Based on the results of a phase I study, 2.0 mg m(-2) was administered as i ntravenous infusion over 5 min every 21 days. Nineteen patients were e ntered into the breast cancer phase II trial and received a total of 5 0 courses (median 2, range 1-6). Of these, dose reductions were perfor med in three courses because of leucopenia or stomatitis (1.5 mg m(-2) , one course; 1.45 mg m(-2), two courses). Twenty-six patients were en tered into the melanoma trial and received a total of 70 courses (medi an 2, range 1-12). No dose reductions were required. All patients were eligible for toxicity. Haematological toxicity included neutropenia C TC grade 3 (29/120 courses, 24.2%) and grade 4 (11/20 courses, 9.2%). Only drug-related CTC grade 1 thrombocytopenia was observed. Non-haema tological toxicity included alopecia in all patients after two courses of treatment as well as CTC grade 3/4 stomatitis and asthenia. In the breast cancer study, one patient achieved a more than 50% tumour redu ction after six cycles but was progressing after 6 weeks. Another pati ent showed a partial remission after the first course but was taken of f the study because of CTC grade 3 skin toxicity. One patient was not evaluable for response (early death). No objective remissions were obs erved in 15 evaluable patients. In melanoma, no objective remissions w ere observed. We conclude that rhizoxin can be safely administered at 2.0 mg m(-2) every 3 weeks. However, it has little activity in patient s with advanced breast cancer and melanoma.