Gemcitabine Plus Irinotecan as First-Line Weekly Therapy in Locally Advanced and/or Metastatic Pancreatic Cancer

Abstract

Single-agent gemcitabine has been established as standard treatment for advanced pancreatic cancer since clinical studies have shown an improvement in overall survival and significant clinical benefit when compared to the best supportive care despite low overall objective response. Several phase II studies have tested other single agents and different gemcitabine-based regimens in pancreatic cancer, but both response and survival rates have remained low. Irinotecan, a topoisomerase I inhibitor currently approved for the treatment of metastatic colon cancer, has also demonstrated improved response rate in patients with pancreatic cancer. Our purpose was to determine the activity and toxicity of this regimen in patients with unresectable or metastatic pancreatic cancer. Patients with histologically confirmed pancreatic adenocarcinoma received gemcitabine 1000 mg/m2 plus irinotecan 100 mg/m2 IV on days 1, 8, and 15 of a 28-day cycle for 6-8 months. From February 2004 to April 2006, 33 patients were entered into this study, 32 of whom were evaluable for treatment response, toxicity, median time to progression, and median survival. Characteristics included a median age of 63 years (range 41-79), 21 males (64%), and 12 females (36%). One patient discontinued treatment due to adverse effects. The total number of cycles administered was 188 and the median number of cycles for patients was 5.6 (range 2-7). Thirty-two patients were assessable for toxicity and response. Grade 3 hematological toxicity occurred in 9% of patients and was primarily neutropenia. No grade >2 gastrointestinal toxicities or death due to treatment were observed. The most frequent nonhematological adverse event was fatigue. Ten patients responded to treatment with two complete responses (6.3%) and eight partial responses (25.0%), for an overall response rate of 31.3%; 11 patients achieved stable disease (34.3%). The median time to tumor progression and the median survival were 9.2 (95% CI: 6.0-12.4) and 11.8 (95% CI: 7.7-15.9) months, respectively, with a 2-year survival of 22%. On the basis of this trial, the combination of gemcitabine plus irinotecan, administered in a weekly schedule and at this dose, is well tolerated and offers encouraging activity in the treatment of advanced and/or metastatic pancreatic cancer.

A review of clinical trials of chemotherapy for pancreatic cancer

“…Before 2006, some trials had explored the combination and several achieved positive results. Similar results were reported by Neri et al (2009) with 33 patients enrolled. Of 32 evaluable patients, 10 responded to treatment (2 complete responses and 8 partial responses) and 11 got stable diseases.…”

“…In a small trial reported by Neri et al (2009), long median time to progression (9.2 months) and overall survival (11.8 months) were observed in the combination of gemcitabine and irinotecan. However, a multicenter phase III trial (Stathopoulos et al, 2006), which seemed more convincing due to the large sample size and the establishment of control group, did not gain meaningful difference between this combination and gemcitabine alone groups.…”

Randomized trials in exocrine pancreatic cancer

“…Dwa badania z randomizacją nad terapią łączoną gemcytabiną z irinotekanem wskazują także, że połączenie tych związków może być korzystne [52,53]. Połączenie gemcytabiny z uracylem lub tegafurem nie miało przewagi nad stosowaniem gemcytabiny w monoterapii [54].…”