Researchers from the Seattle Cancer Treatment and Wellness Center have reported significant and prolonged responses in 7 patients with metastatic pancreatic cancer treated with weekly Taxol (paclitaxel), Eloxatin(oxaliplatin), leucovorin, and 5-FU for 12 weeks. The details of this small phase II study were presented at the 2007 Gastrointestinal Symposium in Orlando Florida sponsored by the American Society of Clinical Oncology.

Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States. Treatment for advanced or metastatic disease typically consists of single-agent Gemzar or Gemzar in combination with other agents. Recent clinical trials report response rates of 12-47%, median survivals of less than one year and one year survivals of 20-47% for patients with advanced unresectable pancreatic cancer treated with several two or three drug combinations. There is evolving evidence that the addition of a platinum compound to Gemzar can improve responses and possibly overall outcomes of patients with advanced pancreatic cancer.

Recently, researchers from Germany have reported that the addition of Eloxatin® or Platinol® (cisplatin) to Gemzar® (gemcitabine) improves progression-free and overall survival in patients with advanced pancreatic cancer. The results of this meta-analysis of two randomized German trials involving over 500 patients were presented at the 2006 annual meeting of the American Society of Clinical Oncology. A second report at the same meeting suggested that Avastin® (bevacizumab) could be added to a regimen of Gemzar and Eloxatin without increasing toxicity and may improve outcome of patients with advanced pancreatic cancer (see related news).

The current clinical trial evaluated a regimen of Taxol (60 mg/m2), Eloxatin (50 mg/m2), leucovorin (20 mg/m2) and 5-FU (425 mg/m2) given weekly for 12 weeks in 7 patients with metastatic pancreatic cancer. Five of the 7 treated patients had received prior chemotherapy. In addition, one patient received Erbitux® (cetuximab) intermittently. All patients also received glutathione, calcium and magnesium to reduce oxaliplatin induced neuropathy. This author reported that all 7 patients had a clinical response and all patients had a greater than 50% reduction of CA 19-9 levels after 12 weeks of therapy. Two patients with elevated bilirubin levels had return to normal levels. Four patients are currently alive 4.8 to 19.7 months following completion of therapy and 3 patients died at 6.7, 10.4 and 10.8 months after completion of therapy. Four patients have survived 12-24.8 months from diagnosis. However, the median survival for the entire group from diagnosis was 12 months. It was concluded that this regimen had significant activity for the treatment of patients with metastatic pancreatic cancer.

Comments: This is a very small study with better than average results, especially in terms of observing a biochemical and clinical response in all patients. These results are even more remarkable given that 5 of the 7 patients had failed prior chemotherapy. It would be of interest to evaluate this regimen in a formal phase III clinical trial if further phase II data holds up. However, in most clinical trials of advanced pancreatic cancer it takes the enrollment of large numbers of patients to detect improvements in therapy. For example, the Eloxatin and Traceva trials listed below both enrolled over 500 patients with advanced pancreatic cancer.

References:Chue BM. Early results of weekly, metronomic dosing of paclitaxel, oxaliplatin, leucovorin and 5-FU (POLF) in the treatment of metastatic pancreatic cancer (PC). 2007 Gastrointestinal Symposium, American Society of Clinical Oncology, abstract 230.http://gicancers.asco.org

Related News:

Gemzar® Combined with Eloxatin® or Platinol® Improves Survival for Patients with Advanced Pancreatic Cancer (7/16/2006)

Gemzar® Plus Oxaliplatin is a Well Tolerated Palliative Combination for Patients with Advanced Pancreatic Cancer  (4/22/2002)

Addition of Tarceva™ to Gemzar® Improves Survival in Pancreatic Cancer  (5/15/2005)

Gemzar® - New Standard of Care in Adjuvant Therapy for Pancreatic Cancer  (5/15/2005)