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Optimizing Chemotherapy Scheduling Using Local Search Heuristics

Institute for Medical Biomathematics, 10 Ha'Teena Street, P.O.B. 282, 60991 Bene-Ataroth, Israel, and Optimata Ltd., 11 Tuval Street, Ramat Gan 52522, Israel
School of Mathematical Sciences, Tel Aviv University, Tel Aviv 69978, Israel
School of Mathematical Sciences, Tel Aviv University, Tel Aviv 69978, Israel, and The Academic College of Tel-Aviv-Yaffo, 4 Antokolsky Street, Tel Aviv 61161, Israel
agur{at}imbm.org
hassin{at}post.tau.ac.il
levy{at}post.tau.ac.il

We develop a method for computing efficient patient-specific drug protocols. Using this method, we identify two general categories of anticancer drug protocols, depending on the temporal cycle parameters of the host and cancer cells: a one-time intensive treatment, or a series of nonintensive treatments. Our method is based on a theoretical and experimental work showing that treatment efficacy can be improved by determining the dosing frequency on the drug-susceptible target and host cell-cycle parameters. Simulating the patient's pharmaco-dynamics in a simple model for cell population growth, we calculate the number of drug susceptible cells at every moment of therapy. Local search heuristics are then used to conduct a search for the desired solution, as defined by our criteria. These criteria include the patient's state at the end of a predetermined time period, the number of cancer and host cells at the end of treatment, and the time to the patient's cure. The process suggested here does not depend on the exact biological assumptions of the model, thus enabling its use in a more complex description of the system. We test three solution methods. Simulated annealing is compared to threshold acceptance and old bachelor acceptance, which are less known variants to this method. The conclusions concerning the three approximation methods are that good results can be achieved by choosing the proper parameters for each of the methods, but the computational effort required for achieving good results is much greater in simulated annealing than in the other methods. Also, a large number of iterations does not guarantee better solution quality, and resources would be better used in several short searches with different parameter values than in one long search.

Subject classifications: health care: treatment.
History: Received July 2000; revision received September 2005; accepted October 2005.

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