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Phase Ib Trial of Nab-Paclitaxel Plus Gemcitabine, Capecitabine, and Cisplatin (Paxg Regimen) in Patients with Stage III Pancreatic Adenocarcinoma
Annals of Oncology 25 (Supplement 4): iv210–iv253, 2014 doi:10.1093/annonc/mdu334.96
711P
PHASE IB TRIAL OF NAB-PACLITAXEL PLUS GEMCITABINE, CAPECITABINE, AND CISPLATIN (PAXG REGIMEN) IN PATIENTS WITH STAGE III PANCREATIC ADENOCARCINOMA
M. Reni1, C. Belli1, G. Balzano2, S. Cereda1, R. Nicoletti3, G. Pepe4, C. Sessa5, S. Cappio3, C. Doglioni6, V. Palazzo1, D. Ceraulo1, L. Gianni1 1 Oncology, IRCCS San Raffaele, Milan, ITALY 2 Surgery, IRCCS San Raffaele, Milan, ITALY 3 Radiology, IRCCS San Raffaele, Milan, ITALY 4 Nuclear Medicine, IRCCS San Raffaele, Milan, ITALY 5 Division of Oncology, IOSI Istituto Oncologico Svizzera Italiana Ospedale Regionale Bellinzona e Valli, Bellinzona, SWITZERLAND 6 Pathology, IRCCS San Raffaele, Milan, ITALY
abstracts
Aim: Gemcitabine (GEM) and nab-paclitaxel (nab-P) significantly improved overall survival over GEM in metastatic pancreatic adenocarcinoma (PA). Given the synergism of taxanes with platinum compounds and fluoropyrimidines, we determined the recommended phase 2 dose (RP2D) of nab-P in combination with cisplatin, capecitabine, and GEM (PAXG regimen) in a phase Ib trial in patients ( pts) with stage III PA (NCT01730222).
Methods: GEM, cisplatin and capecitabine were given at fixed dose (800, 30, and 1250 mg/m2, respectively) q 2 weeks. Doses of nab-P were escalated in cohorts of 3 to 6 pts from 100 (level 1), to 125 (level 2) and 150 mg/m2 (level 3) q 2 weeks. The maximum tolerated dose (MTD) was defined as the dose at which > 2 out of 3-6 pts developed dose-limiting toxicity (DLT) during the first month of therapy. DLT was defined as G ≥ 4 neutropenia lasting ≥ 7 days; G ≥ 3 febrile neutropenia, fever ≥38.5°C, thrombocytopenia, diarrhea, nausea or vomiting; G ≥ 2 neurological toxicity or failure to recover to grade ≤ 1 toxicity (except alopecia) or to baseline values after delaying the initiation of next cycle by > 2 weeks. Results: Between Dec 2012 and Mar 2014, 23 pts (16 males; median age 63 years) with unresectable (according to a surgical team performing >100 duodenocephalopancreasectomy/year) stage III PA, were enrolled at a single institution (3 at level 1, 5 at level 2, 15 at level 3). To date, 197 cycles of PAXG were administered. Therapy is ongoing in 5 pts at level 3. No DLT has occurred. Worse per patient toxicity was G3/4 neutropenia 29/29%; G3 fatigue 14%; G3 neuropathy, anemia, nausea, diarrhea 7%. After 123 cycles at 150 mg/m2 the nab-P dose-intensity was 90%. To date, a partial response (PR) was observed in 15 pts (65%) and stable disease (SD) in 8 pts; among 20 pts with positive PET scan a complete response was observed in 8 (40%), PR in 10 (50%), SD in 2; 19 pts had elevated basal CA19-9 which was reduced by >50% in 18 (95%); 15/16 (94%) pts with mature follow-up were progression-free at 6 months from therapy start. Conclusions: The RP2D of nab-P in the PAXG regimen was 150 mg/m2 every 2 weeks. Preliminary results are promising and a phase II randomized trial with this regimen is ongoing. Disclosure: M. Reni: Participation in an Advisory Board : Merck; Celgene; CLOVIS; Genentech; Boehringer L. Gianni: advisory board Celgene. All other authors have declared no conflicts of interest.
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/iv241/2241519 by National Science and Technology Library -Root user on 25 October 2019
gastrointestinal tumours, non-colorectal
711P
PHASE IB TRIAL OF NAB-PACLITAXEL PLUS GEMCITABINE, CAPECITABINE, AND CISPLATIN (PAXG REGIMEN) IN PATIENTS WITH STAGE III PANCREATIC ADENOCARCINOMA
M. Reni1, C. Belli1, G. Balzano2, S. Cereda1, R. Nicoletti3, G. Pepe4, C. Sessa5, S. Cappio3, C. Doglioni6, V. Palazzo1, D. Ceraulo1, L. Gianni1 1 Oncology, IRCCS San Raffaele, Milan, ITALY 2 Surgery, IRCCS San Raffaele, Milan, ITALY 3 Radiology, IRCCS San Raffaele, Milan, ITALY 4 Nuclear Medicine, IRCCS San Raffaele, Milan, ITALY 5 Division of Oncology, IOSI Istituto Oncologico Svizzera Italiana Ospedale Regionale Bellinzona e Valli, Bellinzona, SWITZERLAND 6 Pathology, IRCCS San Raffaele, Milan, ITALY
abstracts
Aim: Gemcitabine (GEM) and nab-paclitaxel (nab-P) significantly improved overall survival over GEM in metastatic pancreatic adenocarcinoma (PA). Given the synergism of taxanes with platinum compounds and fluoropyrimidines, we determined the recommended phase 2 dose (RP2D) of nab-P in combination with cisplatin, capecitabine, and GEM (PAXG regimen) in a phase Ib trial in patients ( pts) with stage III PA (NCT01730222).
Methods: GEM, cisplatin and capecitabine were given at fixed dose (800, 30, and 1250 mg/m2, respectively) q 2 weeks. Doses of nab-P were escalated in cohorts of 3 to 6 pts from 100 (level 1), to 125 (level 2) and 150 mg/m2 (level 3) q 2 weeks. The maximum tolerated dose (MTD) was defined as the dose at which > 2 out of 3-6 pts developed dose-limiting toxicity (DLT) during the first month of therapy. DLT was defined as G ≥ 4 neutropenia lasting ≥ 7 days; G ≥ 3 febrile neutropenia, fever ≥38.5°C, thrombocytopenia, diarrhea, nausea or vomiting; G ≥ 2 neurological toxicity or failure to recover to grade ≤ 1 toxicity (except alopecia) or to baseline values after delaying the initiation of next cycle by > 2 weeks. Results: Between Dec 2012 and Mar 2014, 23 pts (16 males; median age 63 years) with unresectable (according to a surgical team performing >100 duodenocephalopancreasectomy/year) stage III PA, were enrolled at a single institution (3 at level 1, 5 at level 2, 15 at level 3). To date, 197 cycles of PAXG were administered. Therapy is ongoing in 5 pts at level 3. No DLT has occurred. Worse per patient toxicity was G3/4 neutropenia 29/29%; G3 fatigue 14%; G3 neuropathy, anemia, nausea, diarrhea 7%. After 123 cycles at 150 mg/m2 the nab-P dose-intensity was 90%. To date, a partial response (PR) was observed in 15 pts (65%) and stable disease (SD) in 8 pts; among 20 pts with positive PET scan a complete response was observed in 8 (40%), PR in 10 (50%), SD in 2; 19 pts had elevated basal CA19-9 which was reduced by >50% in 18 (95%); 15/16 (94%) pts with mature follow-up were progression-free at 6 months from therapy start. Conclusions: The RP2D of nab-P in the PAXG regimen was 150 mg/m2 every 2 weeks. Preliminary results are promising and a phase II randomized trial with this regimen is ongoing. Disclosure: M. Reni: Participation in an Advisory Board : Merck; Celgene; CLOVIS; Genentech; Boehringer L. Gianni: advisory board Celgene. All other authors have declared no conflicts of interest.
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/iv241/2241519 by National Science and Technology Library -Root user on 25 October 2019
gastrointestinal tumours, non-colorectal