1. Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer
- Author
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Jia Li, Indukala Doddamane, Annmarie Boustani, Jill Lacy, Charles Cha, Xiangyu Cong, Yanhong Deng, Stacey Stein, Edward Samuel James, Carol Staugaard, Jeremy S. Kortmansky, Bryan W. Chang, Ronald R. Salem, Howard S. Hochster, and Vatsal Patel
- Subjects
Male ,Oncology ,Cancer Research ,Lung Neoplasms ,Organoplatinum Compounds ,FOLFIRINOX ,Leucovorin ,Phases of clinical research ,urologic and male genital diseases ,Bolus (medicine) ,0302 clinical medicine ,metastatic pancreatic cancer ,immune system diseases ,Antineoplastic Combined Chemotherapy Protocols ,Prospective Studies ,Peritoneal Neoplasms ,Liver Neoplasms ,Middle Aged ,Prognosis ,locally advanced pancreatic cancer ,3. Good health ,Oxaliplatin ,Survival Rate ,Tolerability ,Fluorouracil ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Female ,030211 gastroenterology & hepatology ,Folfirinox Regimen ,medicine.drug ,Adult ,medicine.medical_specialty ,Locally advanced ,Adenocarcinoma ,Filgrastim ,Irinotecan ,03 medical and health sciences ,Pancreatic cancer ,Internal medicine ,medicine ,Humans ,Survival rate ,Aged ,Neoplasm Staging ,business.industry ,medicine.disease ,Surgery ,Pancreatic Neoplasms ,Clinical Study ,Camptothecin ,business ,Follow-Up Studies - Abstract
395 Background: Toxicities associated with FOLFIRINOX have prompted use of modifications, despite absence of prospective data validating comparable efficacy and improved tolerability. To determine the impact of attenuated doses of irinotecan and bolus 5FU on efficacy and tolerability, we conducted a prospective phase II study of modified FOLFIRINOX in advanced PC. The efficacy of a FOLFIRINOX regimen has not been previously examined in locally advanced PC (LAPC). Previous studies in LAPC have compared chemo vs chemoRT with median OS in the 9-12 mo range (Loehrer et al, Chauffert et al, Hammel et al). Methods: Previously untreated pts with MPC or LAPC received modified FOLFIRINOX with pegylated filgrastim. Irinotecan and bolus FU were reduced by 25%. AEs were compared to historical control (Conroy et al NEJM 2011). Objective RR in MPC was compared to historical control. PFS and OS were calculated for both cohorts. Results: 31 and 44 pts with LAPC and MPC enrolled. Treatment-related grade 3 and 4 AEs were diarrhea (16.2%), neutropenia (12.2%), fatigue (12.2%), thrombocytopenia (9.5%), anemia (5.4%). Neutropenia (p < 0.0001), vomiting (p = 0.001), and fatigue (p = 0.01) were significantly decreased compared to historical control patients. In MPC, the RR (35.1%) was similar to the historical control group (36.3%; p 0.82); median PFS and OS were 6.1 months (95% CI, 5.19 to 8.31) and10.2 months (95% CI, 7.65 to 14.32) respectively. In LAPC, the RR was 17.2% and median PFS and OS were 17.8 mo (95% CI, 11.0 to 23.9) and 26.6 mo (95% CI, 16.7, NA) respectively. 13 pts went on to surgical resection with 10 now alive and 6 without recurrence. We found no significant association between early metabolic response by FDG-PET imaging and PFS and OS. Conclusions: In this first prospective study of modified FOLFIRINOX, the regimen was well tolerated and associated with decreased incidence of AEs compared to historical control of standard FOLFIRINOX. In MPC pts, the efficacy of the modified regimen appear uncompromised. In this first prospective study of a FOLFIRINOX regimen in LAPC, the PFS and OS surpasses that of previously studied regimens in LAPC. Clinical trial information: NCT01523457.
- Published
- 2016
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