A randomized phase II trial of two different four-drug combinations in advanced pancreatic adenocarcinoma: Cisplatin, capecitabine, gemcitabine plus either epirubicin or docetaxel

• Published in: Journal of clinical oncology Vol. 27; no. 15_suppl; p. 4614
• Main Authors: Cereda, S., Rognone, A., Ghidini, M., Rezzonico, S., Passoni, P., Mazza, E., Nicoletti, R., Zerbi, A., Villa, E., Reni, M.
• Format: Journal Article
• Language: English
• Published: 20.05.2009
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.2009.27.15_suppl.4614

Abstract only 4614 Background: The combination of cisplatin (P), epirubicin (E), 5-fluorouracil (F) and gemcitabine (G) (PEFG regimen) yielded a progression-free survival at 6 months from treatment start (PFS6) of about 50% and a 1-year overall survival (OS) around 40% in patients with advanced pancreatic adenocarcinoma (PA). The current trial was aimed to assess whether the replacement of E with docetaxel (D) may improve PFS6. Methods: Chemo-naive patients with stage III or metastatic PA, age 18–75y, Karnofsky performance status (PS) >50 received P (30 mg/m 2 day 1), G (800 mg/m 2 day 1) and capecitabine (1250 mg/m 2 /day days 1 to 14) and were randomized to receive either D at 25–30 mg/m 2 day 1 (arm A: PDXG regimen) or E at 30 mg/m 2 day 1 (arm B: PEXG regimen). Cycles were repeated every 14 days for a maximum of 6 months. Tumor was assessed by CT scan every 8 weeks. The Fleming design was used to calculate the sample size on the probability of being PFS6 (primary endpoint). Assuming P0=40% and P1=60%, α .05 and β.10, the study was to enroll 52 patients per arm. The regimen had to be considered of interest with > 26 patients being PFS6. Results: Between July 2005 and September 2008, 105 patients were enrolled at a single institution, stratified by stage and randomized (53 arm A). Patients’ characteristics were (A/B): median age 61/59, PS > 70 92/88%, metastatic disease 66/65%; CA19.9 > upper limit of laboratory normal (ULN) 87/90%, median CA19.9 820/755 UI/mL. To date, 46 patients per arm are assessable for the primary endpoint: PFS6 was 58/54%. One- year OS was 41% in both arms. A partial response was observed in 61/37% of patients. Among assessable patients with basal CA19.9 value > ULN (37 per arm), a major biochemical response (reduction >89%) was observed in 46/35% and a minor biochemical response (reduction between 50 and 89%) in 43/35% of patients. Main per cycle G3–4 toxicity was: neutropenia 4/13%, thrombocytopenia 3/2%, anemia 4/3%, fatigue 6/4%. Conclusions: PEXG yielded similar results when compared to prior series treated by PEFG, suggesting that capecitabine may replace F. The inclusion of D instead of E seems to be promising. The present trial confirms the relevant impact on outcome of advanced PA of four-drug regimens. No significant financial relationships to disclose.