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The anti‐tumor arotinoid RO 40‐8757 protects bone marrow from the toxic effects of 5‐fluorouracil
Author(s) -
Eliason James F.,
Inoue Tomoaki,
Kubota Akiko,
Horii Ikuo,
Hartmann Diethelm
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910570211
Subject(s) - fluorouracil , bone marrow , cancer research , medicine , biology , chemotherapy , pathology
Combination therapy with 5‐Fluorouracil (5‐FU) and the arotinoid Ro 40‐8757 (mofarotene) of established chemically induced mammary tumors in rats was examined. The cytotoxic drug was administered weekly and Ro 40‐8757 was given daily. The dose of Ro 40‐8757 used in this study did not have an effect on tumor burden but, in combination with 5‐FU, significantly enhanced the reduction in tumor burden and tumor number. In order to determine if Ro 40‐8757 had a protective effect on 5‐FU‐treated animals, several studies were performed with non‐tumor‐bearing mice. The 5‐FU was given once a week for 3 weeks at a dose that was lethal only after the third administration. When this treatment was combined with Ro 40‐8757 given 5 times/week, approximately 50% of the mice survived. Examination of the progenitor cell contents of femura and spleens of treated mice indicated that the protective effect of Ro 40‐8757 was manifested at the primitive hemopoietic progenitor cell level. Studies with murine bone marrow cells and human breast‐cancer cell lines in vitro demonstrated that there was no interaction between the 2 drugs at the cellular level, indicating that the arotinoid does not enhance the ability of cells to metabolize 5‐FU. This protective effect of the arotinoid makes it a useful potential partner for combination therapy with 5‐FU. © 1994 Wiley‐Liss, Inc.