Miami, Fla. — Chemotherapy-induced alopecia is considered to be one of the most distressing adverse events resulting from chemotherapeutic treatment regimens, having serious psychosocial ramifications for the patient.

A novel topical application of calcitriol is proving to halt the occurrence of chemotherapy-induced hair loss in neonatal rats receiving chemotherapy, giving much hope and needed relief to patients suffering from this psychologically devastating adverse event.

In a recent study, the secosteroid calcitriol in a proprietary delivery system (Cytotech Labs API 31543) was evaluated for its ability to protect the scalp hair follicles from the development of chemotherapy-induced alopecia following the administration of chemotherapy in neonatal rats.

On day 11, the rats were evenly divided into groups and received intraperitoneally different chemotherapeutic agents and combinations of chemotherapeutic agents including etoposide (1.5 mg/kg daily, for three days), cyclophosphamide (37.5 mg/kg once), cyclophosphamide plus doxorubicin (35 mg/kg once; 2.5 mg/kg daily, for three days), cytarabine (25 mg/kg daily, for seven days) and cytarabine plus doxorubicin (25 mg/kg daily, for seven days; 2.5 mg/kg daily, for three days).

Results

Results showed that alopecia was seen 10 days after the last dose of chemotherapy. In the rats treated with vehicle, a total alopecia was seen, but a localized protection was seen in all of the rats treated with 0.2 micrograms of calcitriol and a total body protection was seen in the group treated with 0.3 micrograms of calcitriol.

"Up until now, there has not been a product that consistently protects against any chemotherapy or against any combination of chemotherapy in patients who develop chemotherapy-induced alopecia. The results of our study indicate that we have found a protection for chemotherapy-induced alopecia in the neonatal rat," says Joaquin Jimenez, M.D., of the department of dermatology and cutaneous surgery at the University of Miami Miller School of Medicine, Miami, Fla., and lead author of the study.

Neonatal rats proved to be ideal in this experiment, because the hair follicles are 100 percent in the first stage of morphogenesis of the growth phase. In comparison, 90 percent of the human hair follicles are in the anagen phase, making this model possibly very similar to a human setting. The goal is to have this novel solution work in humans, and according to Dr. Jimenez, there appears to be no reason why topical calcitriol would not be effective in humans. Current methods used in humans to treat chemotherapy-induced alopecia include mainly scalp cooling, and in animals, biologic response modifiers, growth factors and some cytokines such as interleukin-1. However, Dr. Jimenez says all of these approaches are only moderately effective, if at all, for multiple chemotherapy combination.

Timing

According to Dr. Jimenez, the success of the topical calcitriol therapy relies heavily upon the correct timing of its application. If topical calcitriol is given at the same time as the chemotherapy, no protection is observed. Therefore, it is anticipated that future patients will have to receive the topical treatment before they receive the chemotherapy. In rats, the application of calcitriol appeared to be sufficient six days prior to the start of chemotherapy, but in humans, Dr. Jimenez speculated that patients would need to receive the therapy one to two weeks before chemotherapy is started.

The chemotherapeutic agents used in this study are not only the most common agents used, but also are the most alopecic. Therefore, the positive results seen in this study demonstrate the exquisitely high efficacy in protection that topical calcitriol imparts to the hair follicle following chemotherapy.

In a separate study, neonatal rats were transplanted with a chloro-leukemia cell line (MIA-C51), then received cyclophosphamide (37.5 mg/kg once), and the effects of topical calcitriol were evaluated. Results showed that there was no statistical difference in the cure rate with the chemotherapy, meaning there was no protection of the cancer cell from cyclophosphamide by API 31543. However, there was a protection from chemotherapy-induced alopecia.

"Many chemotherapeutic agents are given in cycles, and patients would probably need to receive this topical application of calcitriol throughout their chemotherapeutic regimen. Just how often and at what dose API 31543 will need to be administered will have to be elucidated in animal pre-clinical trials and in clinical trials," Dr. Jimenez says.