Folfirinox (FFX) and Nab-paclitaxel/Gemcitabine (AG) showed significant improvement in efficacy compared to Gemcitabine alone in metastatic pancreatic cancer (mPC). Alternating AG and FFX may overcome resistance to primary therapy and delay tumor progression. We designed a multicenter phase I-II trial with a new sequential regimen of AG followed by FFX in first-line treatment of mPC. The phase I primary objective was to determine the recommended AG and FFX doses. Primary endpoint was to determine the dose-limiting toxicities (DLTs). The phase II will assess the efficacy of the recommended doses.
AG and FFX were administered sequentially, each AG cycle followed by a FFX cycle. Dose-escalation was:
|One cycle D1 = D57||AG (mg/m2) D1, D8, D15||FFX (mg/m2) D29, D43|
|Dose level||Nab-paclitaxel||Gemcitabine||Oxaliplatin||Irinotecan||LV 5-FU|
|2b||125||1000||70||150||5-FU bolus: 400|
|3||125||1000||85||180||5-FU infusion: 2400|
Chemotherapeutic agents were administered according to standard practice, except for Gemcitabine (10mg/m2/min).
From September 2013 to October 2015, 33 mPC patients were included: 7, 6 and 7 patients in levels 1, 2a and 2b, respectively, and 13 in level 3. 31 patients were evaluable for tolerance (2 not evaluable at levels 1 and 2b). Patients' characteristics at baseline were: male 54.8%, median age 61 years (42-75), ECOG PS 0 (35.5%) or 1 (64.5%). Five DLTs were reported: 1, 2 and 2 in levels 2a, 2b and 3, respectively. All DLTs were grade 4 transient, asymptomatic neutropenia with spontaneous resolution. They occurred at treatment initiation, probably due to the absence of prophylactic GCSF treatment during AG administration. There was no limiting neurotoxicity. Promising efficacy results (response and survival) will be presented at the meeting.
This new regimen alternating AG and FFX shows acceptable toxicity and promising efficacy results. The recommended dose (level 3) is being confirmed in a 12 patient-expansion cohort before starting the phase II accrual.
Clinical trial identification
Legal entity responsible for the study
Institut régional du Cancer de Montpellier (ICM), France
This project was supported by Celgene.
E. Assenat: Honoraria: Ipsen, Novartis, Sanofi Consulting. Advisory Role: Ipsen. Research Funding: Bayer (Institution), Celgene (Institution). Travel, Accomodations, Expenses: Novartis, Celgene.
C. de la Fouchardiere: Consulting or Advisory Role: Bayer, Celgene Research. Funding: Roche/Genentech (Institution). Travel, Accomodations, Expenses: Ipsen, Bayer, Roche. E. Samalin: Honoraria: Lilly, Sanofi, Amgen, Roche. Consulting or Advisory Role: Amgen, Sanofi, Roche. Research funding: Bayer (institution). Travel, Accommodations, Expenses: Novartis, Lilly, Ipsen, Roche. F. Portales: Honoraria: Sanofi Consulting or Advisory Role: Sanofi. Research funding: Celgene (Institution). Travel, Accommodations, Expenses: Ipsen. T. Mazard: Honoraria: Amgen, Sanofi. Research funding: Roche, Parma AG (Institution). Travel, Accomodations, Expenses: Amgen. M. Ychou: Honoraria: Bayer, Merck-Serono, Roche/Genentech, Celgene. Consulting or Advisory Role: Bayer, Celgene, Roche. All other authors have declared no conflicts of interest.