Sequential first-line treatment with nab-paclitaxel/gemcitabine and FOLFIRINOX in metastatic pancreatic adenocarcinoma: GABRINOX phase Ib-II controlled clinical trial

Autor: C. de la Fouchardière, Marc Ychou, Françoise Desseigne, F. Portales, Caroline Mollevi, S. Iltache, Thibault Mazard, C. Fiess, Antoine Debourdeau, Eric Assenat
Přispěvatelé: Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut du Cancer de Montpellier (ICM), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Herrada, Anthony
Rok vydání: 2021
Předmět:
Male
Cancer Research
FOLFIRINOX
pancreatic cancer
Leucovorin
Deoxycytidine
Gastroenterology
law.invention
nab-paclitaxel
Randomized controlled trial
law
Antineoplastic Combined Chemotherapy Protocols
Original Research
MESH: Aged
MESH: Middle Aged
gemcitabine
Middle Aged
Oxaliplatin
MESH: Antineoplastic Combined Chemotherapy Protocols
Oncology
[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
MESH: Oxaliplatin
Adenocarcinoma
Female
Fluorouracil
MESH: Pancreatic Neoplasms
medicine.symptom
medicine.drug
Adult
medicine.medical_specialty
Paclitaxel
Nausea
[SDV.CAN]Life Sciences [q-bio]/Cancer
Neutropenia
Irinotecan
[SDV.CAN] Life Sciences [q-bio]/Cancer
Albumins
Internal medicine
Pancreatic cancer
medicine
Humans
metastasis
MESH: Paclitaxel
MESH: Irinotecan
Aged
adenocarcinoma
MESH: Humans
business.industry
MESH: Adenocarcinoma
MESH: Deoxycytidine
MESH: Adult
[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
medicine.disease
MESH: Male
[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Gemcitabine
Pancreatic Neoplasms
[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
MESH: Albumins
MESH: Leucovorin
business
MESH: Female
MESH: Fluorouracil
Febrile neutropenia
Zdroj: ESMO Open
ESMO Open, 2021, 6 (6), pp.100318. ⟨10.1016/j.esmoop.2021.100318⟩
ISSN: 2059-7029
DOI: 10.1016/j.esmoop.2021.100318
Popis: Background Nab-paclitaxel/gemcitabine (AG) and FOLFIRINOX (FFX) are promising drugs in metastatic pancreatic cancer (MPC). This study evaluated a new first-line sequential treatment (AG followed by FFX) in MPC that might overcome resistance to primary therapy and delay tumor progression. Patients and methods Patients with histologically/cytologically confirmed MPC were included in a multicentric trial receiving AG (day 1, 8 and 15) followed by FFX (day 29 and 43). In phase Ib, three dose-levels were tested for maximum tolerated dose (MTD) and recommended phase II dose. In phase II, the main outcome was the objective response rate (ORR) and secondarily safety, progression-free survival (PFS) and overall survival (OS). Results In phase Ib, we included 33 patients (31 assessable) of median age 61.0 years (range 42-75 years) and represented by 54.8% males. Five dose-limiting toxicities were reported without any death. The main grade 3/4 toxicities were neutropenia with spontaneous resolution (35.5%/32.3%), venous thromboembolism (grade 3: 22.6%) and thrombopenia (grade 3: 29.0%), while the MTD was not reached. In phase II, we included 58 patients of median age 60 years (range 34-72 years), 50% males and with Eastern Cooperative Oncology Group stage score 0 and 1 of 37.9% and 62.1%, respectively. They received a median of 4 (1-9) cycles in 8.5 months (0.5-19.8 months). The ORR was 64.9% [95% confidence interval (CI) 51.1% to 77.1%], and neurotoxicity was remarkably low. The main grade 3-4 toxicities were venous thromboembolism, thrombopenia, neutropenia/febrile neutropenia, nausea, diarrhea, weight loss and asthenia without any death. Tumor response was complete in 3.5% and partial in 61.4%, while disease was stable in 19.3% and progressive in 15.8% of patients. The median PFS was 10.5 months (95% CI 6.0-12.5 months) and median OS was 15.1 months (95% CI 10.6-20.1 months). Conclusion Sequential AG and FFX showed acceptable toxicity as first-line treatment with no limiting neurotoxicity, while high response rate and survival justify randomized trials.
Highlights • AG and FFX are promising drugs in MPC. • We hypothesize that nab-paclitaxel by targeting tumor microenvironment would increase FFX access in sequential treatment. • Phase Ib-II trial with AG followed by FFX showed acceptable toxicity with no limiting neurotoxicity. • The high response rate and promising survival justify a further randomized trial.
Databáze: OpenAIRE
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