Phase II Study of Paclitaxel Plus the Protein Kinase C... : American Journal of Clinical Oncology (original) (raw)

Original Articles: Gastrointestinal

Phase II Study of Paclitaxel Plus the Protein Kinase C Inhibitor Bryostatin-1 in Advanced Pancreatic Carcinoma

Lam, Anthony P. MD*; Sparano, Joseph A. MD*; Vinciguerra, Vincent MD†; Ocean, Allyson J. MD‡; Christos, Paul MPH, MS‡; Hochster, Howard MD§; Camacho, Fernando MD*; Goel, Sanjay MD*; Mani, Sridhar MD*; Kaubisch, Andreas MD*

From the *New York Cancer Consortium (www.newyorkcancerconsortium.org), including the Montefiore-Einstein Cancer Center, Bronx, NY; †North Shore University Hospital, Manhasset, New York; ‡New York Presbyterian-Cornell Medical Center, New York, New York; and §New York University Medical Center, New York, New York.

Supported by a contract from the National Institute of Health, National Cancer Institute (N01-CM-62204) (to J.A.S.).

Presented in part at the 2004 American Society of Clinical Oncology meeting, New Orleans, LA.

Reprints: Joseph A. Sparano, MD, New York Cancer Consortium Coordinating Center, -Weiler Division, Department of Oncology, Montefiore Medical Center, 2 South–Room 47-48, 1825 Eastchester Road, Bronx, NY 10461. E-mail: [email protected].

Abstract

Purpose:

To determine the efficacy and toxicity of the protein kinase C inhibitor bryostatin-1 plus paclitaxel in patients with advanced pancreatic carcinoma.

Methods:

Each treatment cycle consisted of paclitaxel 90 mg/m2 by intravenous infusion over 1 hour on days 1, 8, and 16, plus bryostatin 25 mcg/m2 as a 1-hour intravenous infusion on days 2, 9, and 15, given every 28 days. Patients were evaluated for response after every 2 treatment cycles, and continued therapy until disease progression or prohibitive toxicity. The primary objective was to determine whether the combination produced a response rate of at least 30%.

Results:

Nineteen patients with locally advanced or metastatic pancreatic adenocarcinoma received a total of 52 cycles of therapy (range: 1–10). Patients received the combination as first-line therapy for advanced disease (N = 5) or after prior chemotherapy used alone or in combination with local therapy. No patients had a confirmed objective response. The median time to treatment failure was 1.9 months (95% confidence intervals: 1.2, 2.6 months). Reasons for discontinuing therapy included progressive disease or death in 14 patients (74%) or because of adverse events or patient choice in 5 patients (26%). The most common grade 3 to 4 toxicities included leukopenia in 26%, anemia in 11%, myalgias in 11%, gastrointestinal bleeding in 11%, infection in 10%, and thrombosis in 10%.

Conclusion:

The combination of weekly paclitaxel and bryostatin-1 is not an effective therapy for patients with advanced pancreatic carcinoma.