Insulin-induced Enhancement of Tumor Response

Original Article

Insulin-induced enhancement of antitumoral response to methotrexate in breast cancer patients

Eduardo Lasalvia-Prisco1, 2, 3, 5 , Silvia Cucchi2, 4, Jesús Vázquez2, 3, Eduardo Lasalvia-Galante2, 3, Wilson Golomar2, 3 and William Gordon4

(1) Department of Medicine, School of Medicine, University of Uruguay, Montevideo, Uruguay (2) Interdoctors Medical Center, Montevideo, Uruguay (3) National Cancer Institute, Montevideo, Uruguay (4) PharmaBlood Inc, North Miami Beach, Florida, USA (5) (Former Director of the Department of Medicine, School of Medicine, University of Uruguay, Montevideo, Uruguay and National Cancer Institute, Montevideo, Uruguay), Research & Development Department, PharmaBlood Inc, 2050 NE 163rd Street, 2nd Fl, # 202, North Miami Beach, Florida 33162, USA


Purpose 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.

Patients and 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.

Discussion 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.

Cancer Chemotherapy and Pharmacology ISSN: 0344-5704 (Paper) 1432-0843 (Online) DOI: 10.1007/s00280-003-0716-7 Issue: Volume 53, Number 3

Date: March 2004 Pages: 220 - 224

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