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.


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.
Ku
Geoffrey Y
GY
Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Ilson
David H
DH
Schwartz
Lawrence H
LH
Capanu
Marinela
M
O'Reilly
Eileen
E
Shah
Manish A
MA
Kelsen
David P
DP
Schwartz
Gary K
GK
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D054713:Bryostatins / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D054713:Bryostatins; C046785:bryostatin 1; D017239:Paclitaxel