A randomized phase II trial of two different 4-drug combinations in advanced pancreatic adenocarcinoma: Cisplatin, capecitabine, gemcitabine plus either epirubicin or docetaxel (PEXG or PDXG regimen)

Michele Reni, Stefano Cereda, Alessia Rognone, Carmen Belli, Michele Ghidini, Simonetta Longoni, Clara Fugazza, Sara Rezzonico, Paolo Passoni, Najla Slim, Giampaolo Balzano, Roberto Nicoletti, Stefano Cappio, Claudio Doglioni, Eugenio Villa

Research output: Contribution to journalArticle

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Abstract

Purpose: PEFG regimen (P:cisplatin, E:epirubicin, F:5-fluorouracil, G:gemcitabine) significantly prolonged progression-free (PFS) and overall survival (OS) of patients with advanced pancreatic adenocarcinoma (PA) with respect to standard gemcitabine. The current trial was aimed at assessing whether the replacement of E with docetaxel (D) may improve 6 months PFS (PFS6). Methods: Chemo-naive patients with stage III or metastatic PA received P (30 mg/m 2 day 1 and 15), G (800 mg/m 2 day 1 and 15), and capecitabine (1,250 mg/m 2/day days 1-28, without a break) and were randomized to receive either D at 25-30 mg/m 2 day 1 and 15 (arm A: PDXG regimen) or E at 30 mg/m 2 day 1 and 15 (arm B: PEXG regimen). Cycles were repeated every 28 days for a maximum of 6 months. The Fleming design was used to calculate the sample size on the probability of being PFS6. Assuming P0 = 40% and P1 = 60%, α = 0.05 and β = 0.10; the study was to enroll 52 patients per arm. Results: Between July 2005 and September 2008, 105 patients were enrolled, stratified by stage and randomized. Patients' characteristics were (A/B) the following: median age 61/59, PS >70 92/88%, metastatic disease 66/65%. PFS6 was 58%, and median OS was 11 months in both arms. A partial response was observed in 60/37% of patients. Main per cycle G3-4 toxicity was the following: neutropenia 4/13%, thrombocytopenia 2/4%, anemia 4/4%, and fatigue 6/3%. Conclusions: The inclusion of D instead of E yielded more objective response and less G3-4 neutropenia but did not improve PFS and OS. The present trial confirms the relevant impact on outcome of advanced PA of 4-drug regimens.

Original languageEnglish
Pages (from-to)115-123
Number of pages9
JournalCancer Chemotherapy and Pharmacology
Volume69
Issue number1
DOIs
Publication statusPublished - Jan 2012

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docetaxel
gemcitabine
Epirubicin
Drug Combinations
Cisplatin
Adenocarcinoma
Fluorouracil
Toxicity
Fatigue of materials
Neutropenia
Survival
Pharmaceutical Preparations
Sample Size
Fatigue
Capecitabine
Anemia

Keywords

  • Capecitabine
  • Chemotherapy
  • Cisplatin
  • Docetaxel
  • Gemcitabine
  • Pancreatic cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

Cite this

A randomized phase II trial of two different 4-drug combinations in advanced pancreatic adenocarcinoma : Cisplatin, capecitabine, gemcitabine plus either epirubicin or docetaxel (PEXG or PDXG regimen). / Reni, Michele; Cereda, Stefano; Rognone, Alessia; Belli, Carmen; Ghidini, Michele; Longoni, Simonetta; Fugazza, Clara; Rezzonico, Sara; Passoni, Paolo; Slim, Najla; Balzano, Giampaolo; Nicoletti, Roberto; Cappio, Stefano; Doglioni, Claudio; Villa, Eugenio.

In: Cancer Chemotherapy and Pharmacology, Vol. 69, No. 1, 01.2012, p. 115-123.

Research output: Contribution to journalArticle

Reni, Michele ; Cereda, Stefano ; Rognone, Alessia ; Belli, Carmen ; Ghidini, Michele ; Longoni, Simonetta ; Fugazza, Clara ; Rezzonico, Sara ; Passoni, Paolo ; Slim, Najla ; Balzano, Giampaolo ; Nicoletti, Roberto ; Cappio, Stefano ; Doglioni, Claudio ; Villa, Eugenio. / A randomized phase II trial of two different 4-drug combinations in advanced pancreatic adenocarcinoma : Cisplatin, capecitabine, gemcitabine plus either epirubicin or docetaxel (PEXG or PDXG regimen). In: Cancer Chemotherapy and Pharmacology. 2012 ; Vol. 69, No. 1. pp. 115-123.
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abstract = "Purpose: PEFG regimen (P:cisplatin, E:epirubicin, F:5-fluorouracil, G:gemcitabine) significantly prolonged progression-free (PFS) and overall survival (OS) of patients with advanced pancreatic adenocarcinoma (PA) with respect to standard gemcitabine. The current trial was aimed at assessing whether the replacement of E with docetaxel (D) may improve 6 months PFS (PFS6). Methods: Chemo-naive patients with stage III or metastatic PA received P (30 mg/m 2 day 1 and 15), G (800 mg/m 2 day 1 and 15), and capecitabine (1,250 mg/m 2/day days 1-28, without a break) and were randomized to receive either D at 25-30 mg/m 2 day 1 and 15 (arm A: PDXG regimen) or E at 30 mg/m 2 day 1 and 15 (arm B: PEXG regimen). Cycles were repeated every 28 days for a maximum of 6 months. The Fleming design was used to calculate the sample size on the probability of being PFS6. Assuming P0 = 40{\%} and P1 = 60{\%}, α = 0.05 and β = 0.10; the study was to enroll 52 patients per arm. Results: Between July 2005 and September 2008, 105 patients were enrolled, stratified by stage and randomized. Patients' characteristics were (A/B) the following: median age 61/59, PS >70 92/88{\%}, metastatic disease 66/65{\%}. PFS6 was 58{\%}, and median OS was 11 months in both arms. A partial response was observed in 60/37{\%} of patients. Main per cycle G3-4 toxicity was the following: neutropenia 4/13{\%}, thrombocytopenia 2/4{\%}, anemia 4/4{\%}, and fatigue 6/3{\%}. Conclusions: The inclusion of D instead of E yielded more objective response and less G3-4 neutropenia but did not improve PFS and OS. The present trial confirms the relevant impact on outcome of advanced PA of 4-drug regimens.",
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T1 - A randomized phase II trial of two different 4-drug combinations in advanced pancreatic adenocarcinoma

T2 - Cisplatin, capecitabine, gemcitabine plus either epirubicin or docetaxel (PEXG or PDXG regimen)

AU - Reni, Michele

AU - Cereda, Stefano

AU - Rognone, Alessia

AU - Belli, Carmen

AU - Ghidini, Michele

AU - Longoni, Simonetta

AU - Fugazza, Clara

AU - Rezzonico, Sara

AU - Passoni, Paolo

AU - Slim, Najla

AU - Balzano, Giampaolo

AU - Nicoletti, Roberto

AU - Cappio, Stefano

AU - Doglioni, Claudio

AU - Villa, Eugenio

PY - 2012/1

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N2 - Purpose: PEFG regimen (P:cisplatin, E:epirubicin, F:5-fluorouracil, G:gemcitabine) significantly prolonged progression-free (PFS) and overall survival (OS) of patients with advanced pancreatic adenocarcinoma (PA) with respect to standard gemcitabine. The current trial was aimed at assessing whether the replacement of E with docetaxel (D) may improve 6 months PFS (PFS6). Methods: Chemo-naive patients with stage III or metastatic PA received P (30 mg/m 2 day 1 and 15), G (800 mg/m 2 day 1 and 15), and capecitabine (1,250 mg/m 2/day days 1-28, without a break) and were randomized to receive either D at 25-30 mg/m 2 day 1 and 15 (arm A: PDXG regimen) or E at 30 mg/m 2 day 1 and 15 (arm B: PEXG regimen). Cycles were repeated every 28 days for a maximum of 6 months. The Fleming design was used to calculate the sample size on the probability of being PFS6. Assuming P0 = 40% and P1 = 60%, α = 0.05 and β = 0.10; the study was to enroll 52 patients per arm. Results: Between July 2005 and September 2008, 105 patients were enrolled, stratified by stage and randomized. Patients' characteristics were (A/B) the following: median age 61/59, PS >70 92/88%, metastatic disease 66/65%. PFS6 was 58%, and median OS was 11 months in both arms. A partial response was observed in 60/37% of patients. Main per cycle G3-4 toxicity was the following: neutropenia 4/13%, thrombocytopenia 2/4%, anemia 4/4%, and fatigue 6/3%. Conclusions: The inclusion of D instead of E yielded more objective response and less G3-4 neutropenia but did not improve PFS and OS. The present trial confirms the relevant impact on outcome of advanced PA of 4-drug regimens.

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KW - Capecitabine

KW - Chemotherapy

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KW - Pancreatic cancer

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