Schedule dependent effectiveness of CCNU and 5-fluorouracil in experimental chemotherapy
article
The effect of combination chemotherapy with CCNU and 5-FU given either simultaneously or with a time interval of 24 hr was atudied in the Lewis lung carcinoma and in the mouse osteosarcoma C22LR. Tumour growth delay, number of lung metastases and lung colonies as well as the survival time of mice with and without surgical removal of the primary tumour were used as parameters. Treatment with CCNU followed by 5-FU was the least effective schedule in both tumor lines. In order to evaluate therapeutic gain, the authors also investigated the cell killing effect of both drugs in different schedules on resting and on rapidly proliferating bone marrow stem cells: CCNU followed by 5-FU was the most toxic treatment sequence. Consequently the therapeutic effect (the ratio between effect on tumor and effect on normal tissues) must be low when this sequence is given. If a combination of CCNU and 5-FU is considered for the clinical treatment of gastrointestinal cancer, the most frequently used scheme is a nitrosourea on the first day of a 5-day course of 5-FU. Based on our preclinical studies, we suggest a schedule in which 5-FU is followed within a short time interval by CCNU. Chemicals/CAS: fluorouracil, 51-21-8; lomustine, 13010-47-4; Fluorouracil, 51-21-8; Lomustine, 13010-47-4; Nitrosourea Compounds
Topics
fluorouracillomustinebone marrow cellcancer chemotherapycell killingin vitro studylewis carcinomalung carcinomamouseosteosarcomatheoretical studyAnimalCell SurvivalDrug Therapy, CombinationFluorouracilHematopoietic Stem CellsLomustineLung NeoplasmsMaleMiceNeoplasm MetastasisNeoplasms, ExperimentalNitrosourea CompoundsOsteosarcoma
TNO Identifier
228315
ISSN
02775379
Source
European Journal of Cancer and Clinical Oncology, 13(10), pp. 1123-1131.
Pages
1123-1131
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