According to the National Cancer Institute, pancreatic cancer affects 44,030 Americans annually. Treatment for patients with locally advanced or metastatic disease depends on the stage of the cancer. Surgical treatment for cancer of the head of the pancreas is performed with the Whipple procedure, while distal pancreatectomy is preferred for cancer of the tail of the pancreas. Adjuvant single-agent chemotherapy with gemcitabine is used as a treatment of metastatic pancreatic cancer. Expression of the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) in pancreatic tumors has led to the development of agents such as erlotinib, an EGFR tyrosine kinase inhibitor. Considering that the response rates with single-agent therapy are low, trials of combination second-line therapy for metastatic pancreatic cancer are being conducted.
One such study assessed the efficacy and toxicity of combination therapy involving 5-fluorouracil (5-FU) and leucovorin in combination with irinotecan plus oxaliplatin (FOLFIRINOX) as second-line therapy in metastatic pancreatic adenocarcinoma (MPA).
Irinotecan, a topoisomerase I inhibitor, is used against colorectal cancer in patients refractory to 5-FU treatment, and the combination of docetaxel and irinotecan is an active treatment for advanced pancreatic cancer. 5-FU is an antimetabolite pyrimidine analog that functions as an irreversible inhibitor of thymidylate synthase. Leucovorin, a folic acid analog, protects against the harmful effects of methotrexate. Intravenous oxaliplatin is an antineoplastic alkylating agent approved by the FDA for use with 5-FU and leucovorin to treat stage III colon cancer after surgery.
A retrospective analysis of 27 MPA patients treated with FOLFIRINOX as second-line therapy after progressing on first-line chemotherapy with gemcitabine (mean of 6 treatment cycles per patient) was recently published in Oncology. The dosage cycle was as follows:
1. Oxaliplatin 85 mg/m2 on day 1
2. Irinotecan 180 mg/m2 on day 1
3. Leucovorin 400 mg/m2 on day 1
4. 5-FU 400 mg/m2 as a bolus on day 1 and 2400 mg/m2 as 46-hour continuous infusion biweekly
Treatment tolerance was acceptable, with the relative dose density delivered per patient 92.8% for oxaliplatin, 89.1% for irinotecan, and 96.4% for 5-FU. Grade 3/4 neutropenia was seen in 55.6% of patients. As evaluated by WHO and RECIST criteria, the overall survival was 8.5 months, with median time to progression 5.4 months and median event-free survival 3 months. Overall disease control rate was 63%, and a clinical benefit was seen in 55% of patients.
An ESMO Symposium on Metastases to be held in Zurich, Switzerland, on November 10-11, 2011, will focus on the basic science and clinical impact of lymph node, hematopoietic, brain, lung, liver, and bone metastases, as well as biological rationales for new drugs in development, the use of biomarkers, and prevention of metastases. For more information:http://www.esmo.org/events/esmo-symposium-metastases-2011/program.html.
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