Insulin-induced enhancement of antitumoral response to methotrexate in breast cancer patients.
OBJECTIVE
It has been reported that insulin increases the cytotoxic effect in vitro of methotrexate by as much as 10,000-fold. The purpose of this study was to explore the clinical value of insulin as a potentiator of methotrexate.


METHODS
Included in this prospective, randomized clinical trial were 30 women with metastatic breast cancer resistant to fluorouracil + Adriamycin + cyclophosphamide and also resistant to hormone therapy with measurable lesions. Three groups each of ten patients received two 21-day courses of the following treatments: insulin + methotrexate, methotrexate, and insulin, respectively. In each patient, the size of the target tumor was measured before and after treatment according to the Response Evaluation Criteria In Solid Tumors. The changes in the size of the target tumor in the three groups were compared statistically.


RESULTS
Under the trial conditions, the methotrexate-treated group and the insulin-treated group responded most frequently with progressive disease. The group treated with insulin + methotrexate responded most frequently with stable disease. The median increase in tumor size was significantly lower with insulin + methotrexate than with each drug used separately.


CONCLUSIONS
Our results confirmed in vivo the results of previous in vitro studies showing clinical evidence that insulin potentiates methotrexate under conditions where insulin alone does not promote an increase in tumor growth. Therefore, the chemotherapy antitumoral activity must have been enhanced by the biochemical events elicited in tumor cells by insulin.


CONCLUSIONS
In multidrug-resistant metastatic breast cancer, methotrexate + insulin produced a significant antitumoral response that was not seen with either methotrexate or insulin used separately.
Lasalvia-Prisco
Eduardo
E
Department of Medicine, School of Medicine, University of Uruguay, Montevideo, Uruguay. research@pharmablood.com
Cucchi
Silvia
S
Vázquez
Jesús
J
Lasalvia-Galante
Eduardo
E
Golomar
Wilson
W
Gordon
William
W
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use* / Q000633:toxicity; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007328:Insulin / Q000627:therapeutic use* / Q000633:toxicity; D008727:Methotrexate / Q000627:therapeutic use* / Q000633:toxicity; D008875:Middle Aged
D000964:Antimetabolites, Antineoplastic; D007328:Insulin; D008727:Methotrexate