Phase II studies of bryostatin-1 in patients with advanced sarcoma and advanced head and neck cancer

Background. Bryostatin 1 is a marinederived macrolactone with antineoplasticactivity modulated through protein kinaseC, and with good activity in in vitro and in vivomodels. There are fewdrugs that offer palliation for metastaticsoft-tissue sarcoma and head and neckcancer, and drugs with new mechanisms ofaction warrant detailed disease specificstudy. Patients and methods. Twophase II studies for patients withincurable soft tissue sarcoma (12), or headand neck cancer (12) were conducted. Patients were treated with bryostatin,120 mg/m²/72 hours every 2 weeks for 3cycles prior to re-evaluation. Mostpatients had received priorchemotherapy. Results. No patientshad objective responses to therapy. Sixpatients had brief periods of diseasestabilization. Toxicity was generallymild, with myalgia being prominent (n=8). Hyponatremia, not previously described,occurred in 5 patients. The mechanism ofthis toxicity was unclear. Conclusions. Bryosytatin 1given as a single agent for advanced adult soft tissuesarcoma and head and neck cancer isinactive. Myalgia and hyponatremia werethe predominant toxicities.