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Carcinogenic activity in rats of combined treatment with cyclophosphamide, methotrexate and 5‐fluorouracil
Author(s) -
Habs Michael,
Schmähl Dietrich,
Lin P. Z.
Publication year - 1981
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.2910280116
Subject(s) - cyclophosphamide , methotrexate , medicine , carcinogen , fluorouracil , drug , regimen , chemotherapy , cancer , oncology , pharmacology , pathology , biology , genetics
A total of 240 outbred Sprague‐Dawley rats were treated with 3 different doses of the cyclophosphamide‐methotrexate‐5‐fluorouracil (CMF) regimen adopted from clinical chemotherapy studies in breast cancer patients. Eighty untreated rats served as controls. Individual and total doses of the drugs applied were lower than corresponding doses used in human adjuvant therapy protocols compared on a mg/m 2 basis. Lifelong observation of the animals demonstrated a strong doserelated carcinogenic response to the tested scheme. Main target organs of treatment‐related neoplasms were the nervous system, the hematopoietic and lymphatic tissue, the urinary bladder, and the suprarenal gland. It is concluded that the CMF drug combination evokes carcinogenic responses in several organ systems in the rat and should be regarded as representing a carcinogenic risk to humans. Uncritical clinical use of the three‐drug protocol should be avoided.