Hepatic arterial chemotherapy with raltitrexed and oxaliplatin versus standard chemotherapy in unresectable liver metastases from colorectal cancer after conventional chemotherapy failure (HEARTO): a randomized phase-II study

Autor: Leila Bengrine, François Ghiringhelli, Jean Louis Jouve, Julie Vincent, Julie Blanc, Aurélie Bertaut, Romaric Loffroy, Christophe Borg, Boris Guiu
Přispěvatelé: Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Département d'oncologie médicale [Centre Georges-François Leclerc], UNICANCER-UNICANCER, Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de radiologie et d'Imagerie médicale diagnostique et thérapeutique (CHU de Dijon), 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), Unité de Méthodologie, Biostatistiques et Data Management [Centre Georges François Leclerc]
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Cancer Research
Colorectal cancer
medicine.medical_treatment
Phases of clinical research
Gastroenterology
law.invention
Raltitrexed
0302 clinical medicine
Hepatic Artery
Randomized controlled trial
law
Antineoplastic Combined Chemotherapy Protocols
Liver metastasis
Aged
80 and over
Liver Neoplasms
virus diseases
Standard of Care
General Medicine
Middle Aged
3. Good health
Oxaliplatin
Treatment Outcome
Oncology
030220 oncology & carcinogenesis
Female
France
Colorectal Neoplasms
medicine.drug
Adult
medicine.medical_specialty
animal structures
[SDV.CAN]Life Sciences [q-bio]/Cancer
Thiophenes
03 medical and health sciences
Hepatic arterial infusion
Internal medicine
medicine
Humans
Infusions
Intra-Arterial
Aged
Chemotherapy
business.industry
medicine.disease
digestive system diseases
Irinotecan
030104 developmental biology
Drug Resistance
Neoplasm
Chemotherapy
Cancer
Regional Perfusion
Quinazolines
business
Zdroj: Journal of Cancer Research and Clinical Oncology
Journal of Cancer Research and Clinical Oncology, Springer Verlag, 2019, 145 (9), pp.2357-2363. ⟨10.1007/s00432-019-02970-8⟩
ISSN: 0171-5216
1432-1335
DOI: 10.1007/s00432-019-02970-8⟩
Popis: Hepatic arterial infusion (HAI) of chemotherapy could be used in patients with liver-only metastatic colorectal cancer (mCRC) to fight against chemoresistance. We previously reported the efficacy of raltitrexed plus oxaliplatin (HAI) in a retrospective series. We performed a randomized two-stage phase-II study to evaluate the efficacy of HAI of the combination of raltitrexed and oxaliplatin in refractory mCRC with only liver metastases in comparison with standard of care. Eligible patients had unresectable mCRC and were refractory or intolerant to fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF therapy, and anti-EGFR therapy (for tumors with wild-type KRAS). Patients were randomized between HAI raltitrexed (3 mg/m2 over 1 h) followed by oxaliplatin (130 mg/m2 over 2 h) every 3 weeks and standard of care in a 2:1 ratio. A total of 57 patients (38 in the experimental arm and 19 in the standard of care arm) were to be included. The main objective was to demonstrate 6-month PFS of 45% by intention-to-treat analysis in the experimental arm, compared to theoretical PFS of 20%, with a unilateral alpha risk of 5% and beta risk of 10%. After inclusion of 27 patients, the trial was terminated due to insufficient accrual. In the experimental arm, 11 and 4 patients experienced grade 3 and 4 toxicities, respectively. The most frequent grade 3–4 toxicities were neutropenia, liver toxicity, and abdominal pain. Median progression-free survival was 6.7 months (95% Confidence Interval; 3.9–7.2) in the HAI group and 2.2 months (95% CI 1.2–4.3) with standard of care [HR 0.32 (95% CI 0.14–0.76), p = 0.01]. Median overall survival did not differ between the two groups, at 11.2 months (95% CI 4.8–17.6) for the HAI group and 11.9 months (95% CI 2.8–14.3) for standard of care [HR 0.86 (95% CI 0.36–2.04), p = 0.73]. Although stopped prematurely, this randomized trial provides evidence for the benefit and safety of HAI of a combination of raltitrexed and oxaliplatin in liver-only mCRC with chemoresistant disease.
Databáze: OpenAIRE
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