New Study Compares Chemotherapy Options in Pancreatic Cancer Patients
Approximately 44,000 Americans are diagnosed each year with pancreatic cancer, one of the most progressive and deadliest cancers for both men and women. In June 2010, the American Society of Clinical Oncology presented the FOLFIRINOX treatment: sequential administration of oxaliplatin 85 mg/m2 immediately followed by leucovorin 400 mg/m2 over 2 hours, then irinotecan 180 mg/m2, followed by a bolus dose of 5-fluorouracil 400 mg/m2 [5-FU], and finally, a 2.4-g/m2 46-hour infusion of 5-FU. FOLFIRINOX has become the new standard of care for patients with chemotherapy-naïve metastatic pancreatic cancer and relatively preserved performance statuses. Kevin Sullivan, MD, St. Vincent’s Cancer Center, New York, NY and Peter Kozuch, MD, Department of Medicine, Beth Israel and St Luke’s Roosevelt, New York, NY, recently conducted a review of cancer management for patients with metastatic pancreatic cancer focusing on evidence supporting the role of palliative systemic chemotherapy for advanced pancreatic cancer. Attention is given to patient selection, as well as supportive modalities in the areas of pharmacologic and nutritional support ( Cancer J . 2012;18:633-641).
Prior to FOLFIRINOX, gemcitabine chemotherapy was the mainstay treatment for pancreatic cancer. In a randomized phase 3 trial involving 342 patients, gemcitabine 1000 mg/m2 given intravenously over 30 minutes was compared to FOLFIRINOX. Overall survival (OS) was the primary end point. FOLFIRINOX showed a significant improvement compared to gemcitabine with an endpoint of 11.1 months versus 6.8 months respectively (hazard ratio for death, -0.57, P<.001). After 12 months, 48.4% of the FOLFIRINOX group was still alive compared to 20.6% of the gemcitabine group. Only 6% of the gemcitabine group was alive after 18 months, compared to 18.6% of the FOLFIRINOX group. While FOLFIRINOX has better end point results, it is a highly toxic regimen and led to significantly more grade 3 and 4 myelosuppression, febrile neutropenia, diarrhea, and sensory neuropathy. Filgrastim, used to treat neutropenia, had to be administered to 42.5% of the FOLFIRINOX group and to only 5.3% of the gemcitabine group. Based on the toxicity of FOLFIRINOX, patient selection for this treatment should be done carefully. Those best fit for the administration of FOLFIRINOX are patients with an ECOG (Eastern Cooperative Oncology Group) performance status of at least 1 and a normal level of bilirubin. In one study, only 26% of applicants were considered eligible; the exclusion criteria was poor performance status (64%), aged 76 years or older (22%), hyperbilirubinemia (22%), and inadequate organ function (6%).
Based on their review, Sullivan and Kozuch have acknowledged the limits of both gemcitabine chemotherapy and FOLFIRINOX. Pain management and optimization of nutrition status are two major factors in the quality of life of pancreatic cancer patients. While FOLFIRINOX can provide the statistical improvement desired in cancer treatment, the basic quality of life in patients is greatly lowered by toxicity. Gemcitabine allows for better quality of life, but also results in lower chances of overall improvement with treatment. Until there is a treatment that combines the results of FOLFIRINOX with the life quality of gemcitabine, it is extremely important that physicians use effective guides for patient treatment selection.