The Chronotherapy clinical unit is dedicated to transfer experimental and theoretical results obtained by our translational research teams to clinical practice. Its main activities are:

Design and administration of chronotherapy regimens, and the setting of dedicated technologies and clinical logistics.

♦ Protocols involve the same drugs as the ones utilized in conventional chemotherapies but theit temporal administration are precisely stipulated.Tolerance and efficacy are continuously monitored by Medical Doctors of the Unit.      


Example : the chronoIFLO protocol                                                          

Thanks to drug infusion chronomodulation, it is now possible to safely the four most efficient anticancer drugs against digestive cancers with a satisfaying tolerance and a good efficacy, even in patients who have already received several prior chemotherapy cycles. this drug combination administered in a non-circadian based manner induces severe side effects which led to the decision of offering it only to patients in good general condition which have not received any prior chemotherapy. As an example, the chronoIFLO protocol is administered to patients at home through programmable pumps every 2 to 3 weeks (Figure 1).


Figure 1 : Protocol of cancer chronotherapy involving irinotecan, 5-fluorouracile- leucovorine and oxaliplatin administration (chronoIFLO)


Multi-channel programmable pumps can infuse up to 4 molecules following different doses and schedules (Figure 2). The Unit currently use the electronic pump Mélodie™ (Aguettant, Lyon) which can be programmed via a PC.


Figure 2 : Drug infusion pump for chronotherapy. Those two types of pumps allow for the administration of up to 4 drugs.


 Monitoring patient quality of life and circadian coordination

The clinical unit pays particular attention to the patients' quality of life and symptoms induced by chimiotherapies. The circadian rhythms of rest-activity is a valuable biomarker of the circadian timing system and can nowadays be recorded  by a wrist watch equiped with an accelerometer (Figure 3). Our Laboratory has demonstrated a strict correlation between the disruption of rest-activity rhythm and the incidence of fatigue, loss of appetite and various other symptoms in cancer patients. It is nowadays possible to follow the rest-activity rhythms over several consecutive weeks in individual patients and use this measurement to personalize the treatment to avoid severe side effects and circadian disruption.

 Figure 3 : Rest-activity recording (left panel) by a wrist actimeter (left panel). Chimiotherapy induced an intense fatigue and a circadian disruption of the patient's rest-activity rhythm.


Clinical and translational Research 

In order to improve treatment efficacy against liver metastasis, our Unit have settled down a collaboration with the Surgery and Radiology departments at the hôpital Paul Brousse for hepatic intra-arterial administration of chimiotherapies (Figure 4). Thus, our unit has coordinated the first European clinical trial testingthe adminsitration of three anticancer drugs directly through the hepatic artery (OPTILIV ( ; Institut National du Cancer)).

Figure 4 : the OPTILIV protocol: hepatic intra-arterial chronotherapy of irinotecan, 5-fluorouracile and oxaliplatin.



Unité INSERM U935

Campus du CNRS

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