Phase 1B trial of Nab-paclitaxel plus gemcitabine, capecitabine, and cisplatin (PAXG regimen) in patients with unresectable or borderline resectable pancreatic adenocarcinoma

Michele Reni, Gianpaolo Balzano, Silvia Zanon, Paolo Passoni, Roberto Nicoletti, Paolo Giorgio Arcidiacono, Gino Pepe, Claudio Doglioni, Clara Fugazza, Domenica Ceraulo, Massimo Falconi, Luca Gianni, Michele Reni, Gianpaolo Balzano, Silvia Zanon, Paolo Passoni, Roberto Nicoletti, Paolo Giorgio Arcidiacono, Gino Pepe, Claudio Doglioni, Clara Fugazza, Domenica Ceraulo, Massimo Falconi, Luca Gianni

Abstract

Background: Nab-paclitaxel-gemcitabine combination significantly improved overall survival over gemcitabine in metastatic pancreatic adenocarcinoma. A phase 1b trial was performed (ClinicalTrials.gov number, NCT01730222) to determine the recommended phase 2 dose (RP2D) of nab-paclitaxel in combination with cisplatin, capecitabine, and gemcitabine at fixed dose (800, 30, and 1250 mg m(-2) every 2 weeks, respectively; PAXG regimen).

Methods: Nab-paclitaxel doses were escalated from 100 (level one) to 125 (level two) and 150 mg m(-2) (level three) every 2 weeks in cohorts of 3-6 patients with pathologically confirmed unresectable or borderline resectable pancreatic adenocarcinoma.

Results: Between Dec 2012 and Apr 2014, 24 patients were enroled (3 at level one, 5 at level two, 16 at level three) and received 117 cycles of PAXG. No dose-limiting toxicity occurred and level three was the RP2D. At this dose, nab-paclitaxel dose-intensity was 91%. Worse per patient grade 3/4 toxicity were neutropenia 25/31%; fatigue 19%; anaemia and hand-foot syndrome 12%, nausea 6%, and febrile neutropenia 6%. A partial response (PR) was observed in 16 (67%) and stable disease (SD) in 8 patients (33%). Among 21 patients with a baseline positive positron emission tomography (PET) scan, a complete metabolic response was observed in 9 (43%), PR in 10 (48%), SD in 2. CA19-9 decreased by ⩾49% in all the 19 patients with elevated basal value. Six patients were resected after chemotherapy. Progression-free survival at 6 months (PFS-6) was 96%.

Conclusions: The RP2D of nab-paclitaxel in the PAXG regimen was 150 mg m(-2) every 2 weeks. The preliminary results are promising and warrant further exploration.

Conflict of interest statement

This work was supported by Celgene, which provided funding for the study with an unrestricted grant and the supply of the drug. MR discloses: advisory role for Celgene, Boehringer Ingelheim, Genetech, Lilly, Merck Serono, Baxalta; research funding to his institution from Celgene, PharmaMar, and Novartis; expenses reimbursement from Celgene. GB discloses: advisory role for Celgene. MF discloses: research funding to his institution from Novartis. LG discloses: consulting or advisory role for Roche, Pfizer, GlaxoSmithKline, Synthon, Taiho Pharmaceutical, AstraZeneca, Genomic Health, Merck Sharp & Dohme, Boehringer Ingelheim, Tiziana Pharma, Synaffix, and Celgene; patents/royalties/other intellectual property with Roche. All other authors disclose no conflict of interest.

Figures

Figure 1
Figure 1
CONSORT flow diagram. PD=progressive disease; Pts=patients.

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