Chronotherapy of colorectal cancer.
Chronotherapy consists of chemotherapy delivery according to circadian rhythms. These genetically based rhythms modulate cellular metabolism and cell proliferation in normal tissues. As a result, both the host tolerance and antitumor efficacy of 5-fluorouracil (5-FU) and oxaliplatin (L-OHP), like 30 other anticancer drugs, vary largely according to the dosing time in laboratory rodents. The transfer of this concept to the clinic is aimed primarily at increasing the dose-intensity of the therapy through adjustment of drug-delivery to 24h rhythms in host tolerance. A specific technology (programmable-in-time infusion pumps) enables administration of chronotherapy to fully ambulatory patients. Phase I-III clinical trials show chronotherapy significantly increases tolerance to high doses of cancer drugs and improves antitumor activity in patients with metastatic colorectal cancer. These safe conditions of drug-delivery led to the first demonstration of the high activity of the 5-FU-leucovorin-L-OHP protocol. Chronotherapy with these three drugs also allows surgical removal of previously unresectable liver and lung metastases. This novel medico-surgical management provides hope for the cure of metastatic disease in patients with unresectable colorectal cancer metastases.
Giacchetti
Sylvie
S
Chronotherapy Unit, Federation des maladies Sanguines Immunitaires et tumorales and INSERM EPI 0118, Hĵpital Paul Brousse, Villejuif, France. . sylvie.giacchetti@pbr.ap-hop-paris.fr
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016190:Carboplatin / Q000008:administration & dosage; D019454:Chronotherapy; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000556:secondary / Q000601:surgery; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D051379:Mice; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D018714:Radiotherapy, Adjuvant; D051381:Rats
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D016190:Carboplatin; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin