Insulin Potentiation Therapy (IPT), a chemotherapy-based protocol using insulin as a biological response modifier of the endogenous mechanisms of malignancy to selectively target and enhance anticancer drug effects on cancer cells using greatly reduced doses of these drugs effectively eliminates their dose-related side effects, according to Dr Robert Jay Rowen, president International Association of Oxidative Medicine of San Francisco.

The IPT mechanism involves administration of exogenous insulin with low dose chemotherapy. The ligand effect is a function of receptor concentration. The exogenous insulin alters the cell membrane permeability and increases the intra-cellular dose intensity. At the same time the combination of low-dose chemotherapy and exogenous insulin leads to increased S-phase with increased sensitivity to anti-cancer drugs.

Thus, there is a synergy established between the insulin receptor performance and the IGF receptor performance to the detriment of cancer cell growth and survival, Dr Robert Jay Rowen said.

Though chemotherapy drugs are powerful, effective, cell-killing agents, there are many problems associated with them and in their administration such as-adequate intracellular dose intensity requires the systemic administration of high doses of drugs and lack of tissue specificity for drugs, which lead to widespread dose-related drug side effects.

A study was conducted on insulin-induced enhancement of antitumoral response to methotrexate in breast cancer patients in order to explore the clinical value of insulin as a potentiator of methotrexate with 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 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.

The results showed that 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.

The results confirmed in vivo the results of previous in vitro studies showing clinical evidence that 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.

In multi drug-resistant metastatic breast cancer, methotrexate + insulin produced a significant antitumoral response that was not seen with either methotrexate or insulin used separately, he revealed.