title: Phase 1B trial of Nab-paclitaxel plus gemcitabine, capecitabine, and cisplatin (PAXG regimen) in patients with unresectable or borderline resectable pancreatic adenocarcinoma.
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.
authors.affiliation: Department of Medical Oncology, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Reni
authors.affiliation: Department of Surgery, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy.
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Balzano
authors.affiliation: Department of Medical Oncology, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Zanon
authors.affiliation: Department of Radiotherapy, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Passoni
authors.affiliation: Department of Radiology, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Nicoletti
authors.affiliation: Department of Gastroenterology, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy.
authors.forename: Paolo Giorgio
authors.initials: PG
authors.lastname: Arcidiacono
authors.affiliation: Nuclear Medicine Unit, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy.
authors.forename: Gino
authors.initials: G
authors.lastname: Pepe
authors.affiliation: Pathology Unit, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Doglioni
authors.affiliation: Department of Medical Oncology, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Fugazza
authors.affiliation: Department of Medical Oncology, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Ceraulo
authors.affiliation: Department of Surgery, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Falconi
authors.affiliation: Department of Medical Oncology, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Gianni
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000368:Aged; D000418:Albumins / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D015331:Cohort Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D016019:Survival Analysis; D000093542:Gemcitabine
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D003841:Deoxycytidine; D000069287:Capecitabine; D017239:Paclitaxel; D002945:Cisplatin; D000093542:Gemcitabine