DIDEMNIN-B IN METASTATIC MALIGNANT-MELANOMA - A PHASE-II TRIAL OF THESOUTHWEST-ONCOLOGY-GROUP

Didemnin B is a cyclic peptide isolated from the marine tunicate Tridi demnin cyanophorum. It is a known potent inhibitor of RNA, DNA and pro tein synthesis, with activity against the murine B16 melanoma. Fourtee n patients with disseminated malignant melanoma were evaluated in a So uthwest Oncology Group phase II trial of didemnin B at 4.2 mg/m(2) by 30 min i.v. infusion every 28 days (SWOG-8754). Only patients with no prior chemotherapy were eligible; prior radiation therapy, surgery and at most one prior biologic regimen were allowed. Patients with brain metastasis were eligible only if the disease in the brain had been tre ated and controlled. All patients had to have normal renal and hepatic function and adequate granulocyte and platelet counts, a performance status of 0-2, and bidimensionally measurable disease. Fourteen patien ts were entered on the study; five received one and nine received two courses of didemnin B. No responses were noted among the 11 patients e valuable for response. Five patients developed unusual but reversible hypersensitivity reactions during the second course of therapy. Other toxicity in this trial was nausea and vomiting and diarrhea, none of s everity greater than grade 3. Given the lack of antitumor efficacy and the unusual toxicity, further evaluation of didemnin B in this dose a nd schedule in malignant melanoma is not warranted.