Stage III Pancreatic Cancer
Table 5. Randomized Studies in Stage III Pancreatic Cancer: Median Survival continued...
Gemcitabine has demonstrated activity in patients with pancreatic cancer and is a useful palliative agent.[10,11,12] 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 versus gemcitabine alone (hazard ratio [HR], 0.81; 95% 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.[14,15] 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.
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 considered a standard treatment option for patients with advanced pancreatic cancer.