title: A phase II study of bryostatin 1 in metastatic malignant melanoma.
abstract: Bryostatin 1 is a protein kinase C partial agonist which has both antineoplastic and immune-stimulatory properties, including the induction of cytokine release and expansion of tumour-specific lymphocyte populations. In phase I studies, tumour responses have been observed in patients with malignant melanoma, lymphoma and ovarian carcinoma. The dose-limiting toxicity is myalgia. Sixteen patients (age 35-76 years, median 57 years) with malignant melanoma were treated. All had received prior chemotherapy. In each cycle of treatment, patients received bryostatin 25 degrees g m(-2) weekly for three courses followed by a rest week. The drug was given in PET diluent (10 microg bryostatin ml(-1) of 60% polyethylene glycol, 30% ethanol, 10% Tween 80) and infused in normal saline over 1 h. The principal toxicities were myalgia (grade 2, eight patients and grade 3, six patients) and grade 2 phlebitis (four patients), fatigue (three patients) and vomiting (one patient). Of 15 patients evaluable for tumour response, 14 developed progressive disease. One patient developed stable disease for 9 months after bryostatin treatment. In conclusion, single-agent bryostatin appears ineffective in the treatment of metastatic melanoma in patients previously treated with chemotherapy. It should, however, be investigated further in previously untreated patients.
authors.affiliation: ICRF Medical Oncology Unit, Churchill Hospital, Headington, Oxford, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Propper
authors.forename: V
authors.initials: V
authors.lastname: Macaulay
authors.forename: K J
authors.initials: KJ
authors.lastname: O'Byrne
authors.forename: J P
authors.initials: JP
authors.lastname: Braybrooke
authors.forename: S M
authors.initials: SM
authors.lastname: Wilner
authors.forename: T S
authors.initials: TS
authors.lastname: Ganesan
authors.forename: D C
authors.initials: DC
authors.lastname: Talbot
authors.forename: A L
authors.initials: AL
authors.lastname: Harris
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D054713:Bryostatins; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007783:Lactones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018942:Macrolides; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D054713:Bryostatins; D007783:Lactones; D018942:Macrolides; C046785:bryostatin 1