Table 2.

Summary of some chronotherapeutic approaches applied in cancer therapy.

Effect of Chronotherapy in Chemotherapy
Oxaliplatin	Chronomodulated delivery: peak at 16:00 h.	[83,84,85,86,87,88,89]
Cisplatin	Non-small cell lung cancer:
	Low hematological and gastrointestinal adverse effects in the group following chronotherapy.	[90]
Cisplatin + doxorubicin or pirarubicin	Ovarian cancer:
	Cisplatin in the evening 16:00–20:00) combined with doxorubicin or pirarubicin in the morning (06:00) cause less toxicity/side effects and high tumor response.	[60,81,91]
	Cisplatin + doxorubicin had also tumor response in endometrial carcinoma and bladder cancer.	[91]
Fluorodeoxyuridine	Renal cell carcinoma: Circadian-modulated (68% of the daily dose administered in the evening) administration induces a durable tumor response with little toxicity.	[91]
5-FU	Fewer adverse side effects in digestive cancers. Chronoadministration of oxaliplatin-5FU-leucovorin (ChronoFLO4) produced a survival advantage in males with colorectal cancer.	[88]
Irinotecan	Better tolerability after morning delivery in men and in the afternoon in women with metastatic colorectal cancer.	[93]
Effect of chronotherapy in radiotherapy
	Brain metastasis in patients with non-small cell lung cancer: Better survival in patients treated in the morning (before 12:30 h).	[101]
	High-grade glioma: No differences in survival.	[102]
	Breast cancer: Radiotherapy in the afternoon induced less skin toxicity.	[104]
	Bone metastases: Females treated with radiotherapy in the morning exhibited a higher complete or partial response.	[105]
Effect of chronotherapy on the blood–brain barrier
Temozolomide (TMZ)	Morning administration increases overall survival in patients with methylated MGMT, coinciding with the peak of BMAL1 expression.	[114]
Bortezomib	Night administration induces 70% tumor growth inhibition.	[115]
Effect of chronotherapy on the immune system
LYC-53772 and LYC-54143	RORγ synthetic agonists: Activate BMAL1 transcription, induce T cells differentiation, block regulatory T cell-induced immunosuppression, elevate the secretion of cytokines, induced resistance to PD-L1 inhibition in T cells, and increase the cytotoxic activity of T cells.	[116,117]
SR1078	RORα synthetic agonist: Increases CD8+ T cell response.	[119]
Interferon-β	Better antitumor effect during the day in mice.	[120]
Ipilimumab, Nivolumab, or Pembrolizumab	Melanoma: Morning or early afternoon administration extended overall survival.	[122]