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The pemetrexed/gemcitabine combination in pancreatic cancer
1Director of Gastrointestinal Oncology, Section of Hematology/Oncology, University of Chicago, Chicago, Illinois 60637, USA. hkindler@medicine.bsd.uchicago.edu
Abstract:
Gemcitabine has modest antitumor activity in advanced pancreatic cancer. New agents are clearly needed. Pemetrexed (ALIMTA) is a novel antifolate that inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. Pemetrexed has shown in vitro activity against pancreatic cancer cell lines. In a Phase I trial of pemetrexed, two patients with pancreatic cancer achieved partial responses on the once every 21 days schedule. A Phase II trial of pemetrexed in patients with advanced pancreatic cancer showed an objective response rate of 6%, a one year survival of 28%, and a mild toxicity profile. The combination of pemetrexed and gemcitabine is synergistic in vitro and was broadly active in a Phase I trial. The pemetrexed/gemcitabine combination was evaluated in a Phase II trial in 42 patients with advanced pancreatic cancer. The promising activity observed in this study has led to an ongoing international, randomized, Phase III trial in 520 patients comparing the pemetrexed/gemcitabine combination with gemcitabine alone.
Insights
The combination of pemetrexed and gemcitabine shows promise for advanced pancreatic cancer. A Phase II trial indicated encouraging activity, leading to a larger Phase III study comparing this combination against gemcitabine alone.
Area of Science:
- Oncology
- Medical research
- Pharmacology
Background:
- Gemcitabine offers limited efficacy in advanced pancreatic cancer, necessitating novel therapeutic strategies.
- Pemetrexed, a novel antifolate, exhibits in vitro activity against pancreatic cancer cell lines and targets key enzymes like thymidylate synthase.
- Previous Phase I and II trials of pemetrexed monotherapy demonstrated modest activity and a favorable toxicity profile in advanced pancreatic cancer patients.
Purpose of the Study:
- To evaluate the efficacy and safety of the pemetrexed/gemcitabine combination in patients with advanced pancreatic cancer.
- To assess the synergistic potential of combining pemetrexed with gemcitabine.
- To provide rationale for a Phase III trial comparing the combination therapy with gemcitabine alone.
Main Methods:
- A Phase II clinical trial involving 42 patients with advanced pancreatic cancer.
- Administration of pemetrexed in combination with gemcitabine.
- Evaluation of objective response rate, one-year survival, and toxicity profile.
Main Results:
- The pemetrexed/gemcitabine combination demonstrated promising activity in advanced pancreatic cancer.
- A Phase II trial showed encouraging results, prompting further investigation.
- An ongoing international Phase III trial is comparing this combination against gemcitabine monotherapy in 520 patients.
Conclusions:
- The pemetrexed/gemcitabine combination represents a potentially valuable therapeutic option for advanced pancreatic cancer.
- The observed promising activity warrants further evaluation in a large-scale Phase III clinical trial.
- This combination therapy may offer improved outcomes compared to gemcitabine alone.