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A pilot study of perillyl alcohol in pancreatic cancer
Jesus M Matos1, C Max Schmidt, Howard J Thomas
1Department of Surgery, Indiana University School of Medicine at Indiana University/Purdue University at Indianapolis, Indianapolis, Indiana, USA.
Background:
Chemotherapy has been largely unsuccessful in pancreatic cancer. Measurement of cell-specific biological endpoints may clarify the evaluation of a newer generation of compounds. Perillyl alcohol has shown chemotherapeutic activity in preclinical systems through enhancing apoptosis.
Aims:
To pilot a new trial template for testing novel agents in pancreatic cancer and to assess the biological activity of perillyl alcohol in patients with resectable pancreatic cancer.
Methods:
Apoptosis was quantified with ApopTag in situ, Bak staining, and light microscopy. Tumor size, serum CA 19-9 level, and survival were also measured.
Results:
Eight patients enrolled. Toxicity was mild and perillyl alcohol was generally well tolerated. Tumor size and CA 19-9 level were unchanged with perillyl alcohol treatment. Survival time was longer in patients who received full perillyl alcohol treatment (288 +/- 32 days) compared to those who did not (204 +/- 96 days), but this result did not achieve statistical significance (P = 0.2). There was a trend toward greater apoptosis in patients receiving perillyl alcohol compared to fresh operative controls; there was also a suggestion of greater apoptosis in tumor compared to normal pancreatic tissue in the same patient.
Conclusions:
Incorporation of cell-specific biological endpoints is challenging but feasible and should be used in clinical studies of pancreatic cancer treatment. Our pilot study suggests that perillyl alcohol may indeed have effects on biological endpoints. This study will serve as a useful template for examining cell-specific biological endpoints in the testing of future agents that are thought to induce apoptosis in pancreatic cancer.
Insights
This pilot study explored perillyl alcohol for pancreatic cancer, finding it generally well-tolerated and showing a trend toward increased apoptosis. Further research is needed to confirm its efficacy in pancreatic cancer treatment.
Area of Science:
- Oncology
- Cancer Biology
- Pharmacology
Background:
- Pancreatic cancer chemotherapy remains largely ineffective.
- Novel agents require robust evaluation methods.
- Perillyl alcohol demonstrates preclinical apoptosis-enhancing activity.
Purpose of the Study:
- To pilot a novel trial template for pancreatic cancer drug testing.
- To assess perillyl alcohol's biological activity in resectable pancreatic cancer patients.
Main Methods:
- Quantified apoptosis using ApopTag, Bak staining, and microscopy.
- Monitored tumor size and serum CA 19-9 levels.
- Assessed patient survival time.
Main Results:
- Eight patients completed the study; perillyl alcohol was well-tolerated with mild toxicity.
- No significant changes in tumor size or CA 19-9 levels were observed.
- A trend towards increased apoptosis was noted in perillyl alcohol-treated patients and tumor tissue compared to controls.
Conclusions:
- Integrating cell-specific endpoints into clinical trials is feasible for pancreatic cancer.
- Perillyl alcohol shows potential biological effects in pancreatic cancer.
- This study provides a template for evaluating apoptosis-inducing agents in pancreatic cancer.
