Lay Summary: Gemcitabine and irinotecan appears to be no better than gemcitabine alone
The combination of irinotecan and gemcitabine has been studied in pancreatic cancer. Rocha Lima and colleagues randomized 360 patients to either gemcitabine 1000 mg/m2 and irinotecan 100 mg/m2 on days 1 and 8 every 21 days (gem/irino) or the standard gemcitabine regimen (gem). The arms were well balanced as to age, performance status, metastatic disease, and prior radiotherapy. Diarrhea and nausea/vomiting were worse for patients on the gem/irino arm. While the gem/irino combination was associated with a higher response rate, overall survival and time to tumor progression were similar in both groups. The overall survival for the gem/irino and gem arms was 6.3 months and 6.6 months, respectively. Except for diarrhea, toxicity was very similar between both groups.
The combination of gemcitabine and irinotecan was clearly no better than single-agent gemcitabine. The study that compared the regimens should serve as a cautionary note to investigators regarding phase 2 results. While promising results from the phase 2 study of gemcitabine and irinotecan prompted the launch into this phase 3 trial, it is becoming increasingly clear that response rates in phase 2 trials for pancreatic cancer are often unreliable surrogates for overall survival. For example, in the phase 2 study, the median survival was 5.7 months, which is very similar to the 6.3-month median survival seen in the phase 3 study.
Rocha Lima CM, Sherman CA, Brescia FJ, Brunson CY, Green MR.Irinotecan/gemcitabine combination chemotherapy in pancreatic cancer.Oncology (Williston Park). 2001 Mar;15(3 Suppl 5):46-51.