A multicenter phase III trial comparing irinotecan-gemcitabine (IG) with gemcitabine (G) monotherapy as first-line treatment in patients with locally advanced or metastatic pancreatic cancer

Abstract

Our purpose was to determine the response rate and median and overall survival of gemcitabine as monotherapy versus gemcitabine plus irinotecan in advanced or metastatic pancreatic cancer. Patients with histologically or cytologically confirmed adenocarcinoma who were chemotherapy and radiotherapy naive were enrolled. Patients were centrally randomised at a one-to-one ratio to receive either gemcitabine monotherapy (900 mg m À2 on days 1, 8 and 15 every 4 weeks (arm G), or gemcitabine (days 1 and 8) plus irinotecan (300 mg m À2 on day 8) (arm IG), repeated every 3 weeks. The total number of cycles administered was 255 in the IG arm and 245 in the G arm; the median number of cycles was 3. In all, 145 patients (71 in arm IG and 74 in arm G) were enrolled; 60 and 70 patients from arms IG and G, respectively, were evaluable. A complete clinical response was achieved in three (4.3%) arm G patients; nine (15%) patients in arm IG and four (5.7%) in arm G achieved a partial response. The overall response rate was: arm IG 15% and arm G 10% (95% CI 5.96 -24.04 and 95% CI 2.97 -17.03, respectively; P ¼ 0.387). The median time to tumour progression was 2.8 months and 2.9 months and median survival time was 6.4 and 6.5 months for the IG and G arms, respectively. One-year survival was 24.3% for the IG arm and 21.8% for the G arm. No statistically significant difference was observed comparing gemcitabine monotherapy versus gemcitabine plus irinotecan in the treatment of advanced pancreatic cancer, with respect to overall and 1-year survival.

Metastatic Pancreatic Cancer 2008: Is the Glass Less Empty?

“…Table 3 summarizes 13 randomized phase III trials that attempted to improve upon the survival outcomes achieved with gemcitabine alone, typically by adding a second cytotoxic agent [20,[31][32][33][34][35][36][37][38][39][40][41][42]. With the exception of the gemcitabine plus capecitabine experimental arm reported by Cunningham et al [35] in abstract form only as of this review, these efforts have failed to identify a gemcitabine-based chemotherapy doublet that has produced significantly better median or 1-year survival outcomes.…”

A preclinical evaluation of pemetrexed and irinotecan combination as second-line chemotherapy in pancreatic cancer

“…In fact, not only PMX, as above reported, has demonstrated to be active as single agent but CPT-11 also has demonstrated activity, although modest, in pancreatic cancer (Wagener et al, 1995;Klapdor and Fenner, 2000;Pizzolato and Saltz, 2003). Unfortunately, a recently reported phase III trial of GEM with or without CPT-11 revealed no survival benefit (Rocha Lima et al, 2004;Stathopoulos et al, 2006) but other combinations of CPT-11 should continue to be explored in an effort to further improve the treatment of this chemorefractory disease (Taieb et al, 2006). Secondly, each drug in this combination has an independent mechanism of action.…”

Pancreatic cancer: treatment approaches and trends

“…Many phase II trials have demonstrated the efficacy of gemcitabine-based combinations, which comprise other cytotoxic molecules such as capecitabine, 5-FU, cisplatin, irinotecan [34][35][36][37] or the targeted agents sorafenib and cetuximab [38][39][40] . However, in some randomized phase III trials of gemcitabine based chemotherapy combinations, these combinations failed to show statistically significant improvement in patient's overall survival when compared to gemcitabine used as a single-agent [41][42][43][44][45][46] . Nowadays, gemcitabine is used in combination with taxol, a paclitaxel albumin-stabilized nanoparticle formulation (nab-paclitaxel) that is commercially known as abraxane.…”