Phase II study of pemetrexed plus gemcitabine in advanced pancreatic cancer

Hedy L. Kindler, William M. Dugan, Howard Hochster, Donald K. Strickland, Andrew Jacobs, Anna Marie Hayden, Astra M. Liepa, William J. John

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1 Scopus citations

Abstract

Background: Gemcitabine is the standard chemotherapy for the treatment of advanced pancreatic cancer. The novel multitargeted antifolate pemetrexed (Alimta®) has also demonstrated activity in this disease. These two drugs are synergistic in vitro, and a phase I study has demonstrated activity of single-agent pemetrexed in pancreatic cancer. Aim: To evaluate pemetrexed plus gemcitabine in a multicenter phase II study in patients with advanced pancreatic cancer. Patients and methods: Chemonaive patients with advanced pancreatic adenocarcinoma, metastatic or locally advanced, not amenable to curative resection, received intravenous gemcitabine 1250 mg/m2 over 30 minutes on days 1 and 8 and intravenous pemetrexed 500 mg/m2 over 10 minutes on day 8 every 21 days. The primary endpoint was objective response rate. Patients were evaluated for time-to-event variables including overall survival, time-to progression, time-to-treatment failure, and duration of response. Patients who were symptomatic were evaluated weekly for clinical benefit response. CT scans were obtained every two cycles. Results: Forty-two patients were treated; 41 were evaluable for efficacy. Ninety-five percent of patients had metastatic disease. There were five partial responses (objective response rate 12%), and 44% of patients had stable disease. The 1-year survival rate was 32%; median survival was 6.6 months (95% CI 4.4, 9.9). Of 30 eligible patients, four (13%) had a clinical benefit response. Grade 3 and 4 hematologic toxicities included neutropenia (84%), febrile neutropenia (12%), and thrombocytopenia (33%). Non-hematologic toxicities were minimal. Conclusion: The combination of pemetrexed and gemcitabine is active in advanced pancreatic cancer, and has acceptable toxicity; a 1-year survival rate of 32% is encouraging. A phase III trial comparing pemetrexed plus gemcitabine with gemcitabine has completed accrual.

Original languageEnglish (US)
Pages (from-to)185-191
Number of pages7
JournalAmerican Journal of Cancer
Volume4
Issue number3
DOIs
StatePublished - 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology

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