Phase II trial of sequential paclitaxel and 1 h infusion of bryostatin-1 in patients with advanced esophageal cancer.

Background: We sought to determine the response rate and toxicity profile of sequential paclitaxel and bryostatin-1, a novel, selective inhibitor of protein kinase C, in patients with advanced esophageal cancer.

Patients And Methods: Patients with advanced esophageal and gastroesophageal junction cancer were enrolled. All gave informed consent. They were initially treated with paclitaxel 90 mg/m(2) intravenously on Day 1 and bryostatin-1 50 microg/m2 on Day 2 weekly for three consecutive weeks out of four. Because of severe myalgias, dosing was reduced to paclitaxel 80 mg/m2 with bryostatin-1 40 microg/m2 and then to paclitaxel 80 mg/m2 with bryostatin-1 25 microg/m2.

Results: Twenty-four patients were enrolled, with 22 assessable for response. The partial response rate was 27%. 10 patients treated with bryostatin-1 40-50 microg/m2 had a response rate of 40 versus 17% at bryostatin-1 25 microg/m2 (p-value = 0.3). Median time-to-progression was 3.7 months and median survival was 8.3 months. Grade 3/4 myalgias were seen in 50% of patients. Myalgias appeared to be related to bryostatin-1 dose. Because of toxicity, the trial was closed prior to full accrual.

Conclusions: Despite potential anti-tumor activity of this combination in patients with advanced esophageal cancer, further development is not warranted, given the severe toxicity, especially myalgias, that were seen.