Pancreatic Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Stage IV Pancreatic Cancer
The low objective response rate and lack of survival benefit with current chemotherapy indicates clinical trials as appropriate treatment of all newly diagnosed patients. Occasional patients have palliation of symptoms when treated by chemotherapy with well-tested older drugs such as fluorouracil (5-FU). Gemcitabine has demonstrated activity in patients with pancreatic cancer and is a useful palliative agent.[1,2,3] A phase III trial of gemcitabine versus 5-FU as first-line therapy in patients with advanced or metastatic adenocarcinoma of the pancreas reported a significant improvement in survival among patients treated with gemcitabine (1-year survival was 18% with gemcitabine as compared with 2% with 5-FU, P = .003).[Level of evidence: 1iiA] The National Cancer Institute of Canada performed a phase III trial (CAN-NCIC-PA3 [NCT00026338]) that compared gemcitabine alone versus the combination of gemcitabine and erlotinib (100 mg/day) in patients with advanced or metastatic pancreatic carcinomas. They showed that the addition of erlotinib modestly prolonged survival when combined with gemcitabine alone (hazard ratio [HR], 0.81; 95% confidence interval [CI], P = .038). The corresponding median and 1-year survival rates for patients who received erlotinib versus placebo were 6.2 months and 5.9 months, and 23% versus 17%, respectively.[Level of evidence: 1iiA]
Many phase III studies have evaluated a combination regimen with either a platinum analogue (cisplatin or oxaliplatin) or fluoropyrimidine versus single-agent gemcitabine.[5,6] Not one of these phase III trials has demonstrated a statistically significant advantage favoring the use of combination chemotherapy in the first-line treatment of metastatic pancreatic cancer.
Pancreatic cancer often goes undetected until it's advanced and difficult to treat. In the vast majority of cases, symptoms only develop after pancreatic cancer has grown and begun to spread.
Because more than 95% of pancreatic cancer is the adenocarcinoma type, we'll describe those symptoms first, followed by symptoms of rare forms of pancreatic cancer.
A multicenter phase II–III trial included 342 patients with metastatic pancreatic adenocarcinoma with an Eastern Cooperative Oncology Group performance status score of 0 or 1. The patients were randomly assigned to receive FOLFIRINOX (oxaliplatin [85 mg/m2], irinotecan [180 mg/m2], leucovorin [400 mg/m2], and fluorouracil [400 mg/m2] given as a bolus followed by 2400 mg/m2 given as a 46-hour continuous infusion, every 2 weeks) or gemcitabine (1000 mg/m2 weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks). The median OS was 11.1 months in the FOLFIRINOX group compared with 6.8 months in the gemcitabine group (HR for death, 0.57; 95% CI, 0.45–0.73; P < .001).[Level of evidence: 1iiA] Median progression-free survival was 6.4 months in the FOLFIRINOX group and 3.3 months in the gemcitabine group (HR for disease progression, 0.47; 95% CI, 0.37–0.59; P < .001). The objective response rate was 31.6% in the FOLFIRINOX group versus 9.4% in the gemcitabine group (P < .001). FOLFIRINOX was more toxic than gemcitabine; 5.4% of patients in this group had febrile neutropenia. At 6 months, 31% of the patients in the FOLFIRINOX group had a definitive degradation of the quality of life versus 66% in the gemcitabine group (HR, 0.47; 95% CI, 0.30–0.70; P < .001). Therefore, FOLFIRINOX is now considered a standard treatment option for patients with advanced pancreatic cancer.