FOLFIRINOX, a combination chemotherapy regimen consisting of oxaliplatin (Eloxatin, generics), irinotecan (Camptosar, generics), fluorouracil (Adrucil, generics), and leucovorin (Fusilev, generics), was more effective than standard gemcitabine (Gemzar, generics) in increasing survival and delaying disease progression in patients with metastatic pancreatic cancer.
As the nation’s fourth-leading cause of death from cancer in 2010, pancreatic adenocarcinoma carries a grim prognosis: a 5-year survival rate of 6% in the United States as well as in Europe. Gemcitabine became the reference regimen after a randomized trial, published in 2003, showed the agent to improve median overall survival over fluorouracil (5.6 months vs 4.4 months), and subsequent trials of gemcitabine yielded median overall survival of 5.0 to 7.2 months. However, combining the drug with a variety of cytotoxic and targeted agents had not significantly increased patient survival.
Noting that oxaliplatin, irinotecan, fluorouracil, and leucovorin all had some activity against pancreatic cancer and no overlapping toxic effects, Thierry Conroy, MD, of France’s Nancy University and Centre Alexis Vautrin, and colleagues conducted phase 1 and phase 2 trials of FOLFIRINOX that demonstrated responses in persons with advanced pancreatic cancer. The current project is a phase 2-3 trial in which the combination therapy is further compared against single-agent gemcitabine in persons with metastatic pancreatic cancer.
As Conroy and associates described in The New England Journal of Medicine (2011;364:1817), 342 people with metastatic pancreatic cancer were randomized to FOLFIRINOX or gemcitabine for 6 months. Median overall survival was 11.1 months in the FOLFIRINOX group compared with 6.8 months for the gemcitabine group. Median progression-free survival was 6.4 months and 3.3 months, respectively.
FOLFIRINOX did have a less favorable safety profile than gemcitabine, causing more grade 3 or 4 febrile neutropenia, thrombocytopenia, diarrhea, sensory neuropathy, and grade 2 alopecia. However, FOLFIRINOX significantly increased time to definitive deterioration of the quality of life: At 6 months, only 31% of the FOLFIRINOX patients had such a definitive degradation, compared with 66% in the gemcitabine group.
New DRUG indications improve prognosis
The FDA has approved indications for two drugs for a rare, slow-growing pancreatic cancer known as PNET (progressive neuroendocrine tumors located in the pancreas).
Everolimus (Afinitor), an mTOR inhibitor, is approved for use in renal cell carcinoma and subependymal giant cell astrocytoma. Its new indication is for PNET in persons whose tumors have metastasized or cannot be removed surgically. The most commonly reported side effects in the treatment group were stomatitis, rash, diarrhea, fatigue, edema, abdominal pain, nausea, fever, and headache.
Sunitinib (Sutent) is also already on the market for late-stage renal cell carcinoma and for GI stromal tumor. The most commonly reported side effects were diarrhea, nausea, vomiting, fatigue, anorexia, high BP, asthenia, abdominal pain, changes in hair color, stomatitis, and neutropenia. ONA