Daytime versus evening infusions of immune checkpoint inhibitors.

Abstract

The delivery of treatments according to circadian rhythms, known as chronotherapy, has been instrumental in the discovery of oxaliplatin efficacy and safety in colon cancer 1 Lévi F Zidani R Misset JL Randomised multicentre trial of chronotherapy with oxaliplatin, fluorouracil, and folinic acid in metastatic colorectal cancer. Lancet. 1997; 350: 681-686 Summary Full Text Full Text PDF PubMed Scopus (604) Google Scholar and the efficacy of neoadjuvant chemotherapy for liver metastases from colorectal cancer in the late 1990s. 2 Giacchetti S Itzhaki M Gruia G et al. Long-term survival of patients with unresectable colorectal liver metastases following infusional chemotherapy with 5-fluorouracil, leucovorin, oxaliplatin and surgery. Ann Oncol. 1999; 10: 663-669 Summary Full Text PDF PubMed Scopus (589) Google Scholar However, no large trial has tested the chronotherapy hypothesis since 2006, when patients with metastatic colorectal cancer recruited between 1998 and 2002 given FOLFOX (a combination of folinic acid, fluorouracil, and oxaliplatin) had similar overall survival when receiving conventional or fixed-time chronomodulated therapy. 3 Giacchetti S Bjarnason G Garufi C et al. Phase III trial comparing 4-day chronomodulated therapy versus 2-day conventional delivery of fluorouracil, leucovorin, and oxaliplatin as first-line chemotherapy of metastatic colorectal cancer: the European Organisation for Research and Treatment of Cancer Chronotherapy Group. J Clin Oncol. 2006; 24: 3562-3569 Crossref PubMed Scopus (160) Google Scholar However, this trial showed for the first time the need for sex-specific chronotherapy schedules, with a large and significant survival benefit for chronotherapy in men, but not in women. 3 Giacchetti S Bjarnason G Garufi C et al. Phase III trial comparing 4-day chronomodulated therapy versus 2-day conventional delivery of fluorouracil, leucovorin, and oxaliplatin as first-line chemotherapy of metastatic colorectal cancer: the European Organisation for Research and Treatment of Cancer Chronotherapy Group. J Clin Oncol. 2006; 24: 3562-3569 Crossref PubMed Scopus (160) Google Scholar Effect of immunotherapy time-of-day infusion on overall survival among patients with advanced melanoma in the USA (MEMOIR): a propensity score-matched analysis of a single-centre, longitudinal studyOur findings are in line with an increasing body of evidence that adaptive immune responses are less robust when initially stimulated in the evening than if stimulated in the daytime. Although prospective studies of the timing of immune checkpoint inhibitor infusions are warranted, efforts towards scheduling infusions before mid-afternoon could be considered in the multidisciplinary management of advanced melanoma. Full-Text PDF