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New drugs for patients with pancreatic cancer
Daniel D Von Hoff1, David Bearss
1Arizona Cancer Center, Tucson, Arizona 85724-5024, USA. dvonhoff@azcc.arizona.edu
Abstract:
This past year has proved to be a relatively disappointing one for the development of agents that could improve the survival rates of patients with advanced pancreatic cancer. A well designed randomized trial of treatment of patients with gemcitabine with or without a farnesyl transferase inhibitor (tried because pancreatic cancers have a high incidence of K- abnormalities) showed no improvement in survival rates. A definitive randomized controlled trial with a histone deacetylase inhibitor also proved negative. There are some signs of hope in that in early nonrandomized studies there are some new agents that appear to have some activity against the disease. These agents include the thymidylate synthase inhibitor capecitabine (which is possibly activated at the tumor site), the antigastrin immunogen G17DT (which is an immunization designed to neutralize the pancreatic growth factor gastrin), and the topoisomerase I inhibitor 9-nitrocamptothecin. In addition, the combination of the new agent oxaliplatin to high-dose 5FU plus leucovorin, which gave a median survival rate of 12.5 months, is also worthy of further study. Supportive care findings of interest for the patient with advanced pancreatic cancer of note include: the study in which eicosapentaenoic acid (fish oil) caused a modest weight gain (median of 1 kg), and the finding that ofloxacin plus ursodeoxycholic acid was not superior to ursodeoxycholic acid alone for the prevention or occlusion of biliary stents.
Insights
Advanced pancreatic cancer treatments showed limited success this year. While some new agents like capecitabine and oxaliplatin combinations offer hope, survival rates remain a challenge.
Area of Science:
- Oncology
- Gastroenterology
- Cancer Research
Background:
- Pancreatic cancer survival rates have seen minimal improvement with recent therapeutic developments.
- Standard treatments like gemcitabine and histone deacetylase inhibitors have not significantly enhanced patient outcomes in advanced stages.
Observation:
- Early studies indicate potential efficacy for novel agents including capecitabine, G17DT, and 9-nitrocamptothecin.
- A combination of oxaliplatin with high-dose 5-fluorouracil (5FU) and leucovorin demonstrated a median survival of 12.5 months.
- Supportive care research noted modest weight gain with eicosapentaenoic acid (fish oil) and no added benefit of ofloxacin to ursodeoxycholic acid for biliary stent patency.
Findings:
- Randomized trials of gemcitabine with farnesyl transferase inhibitors and histone deacetylase inhibitors yielded negative survival results.
- Non-randomized studies suggest potential activity of capecitabine, G17DT, and 9-nitrocamptothecin against advanced pancreatic cancer.
- The combination of oxaliplatin, 5FU, and leucovorin warrants further investigation for advanced pancreatic cancer treatment.
Implications:
- Despite setbacks, novel therapeutic strategies and supportive care interventions show promise for improving advanced pancreatic cancer management.
- Further research is crucial to validate the efficacy of emerging agents and treatment combinations.
- Optimizing supportive care, such as nutritional interventions, may play a role in patient management.