The protective role of the immunomodulator AS101 against chemotherapy-induced alopecia studies on human and animal models

Benjamin Sredni*, Ren He Xu, Michael Albeck, Uzi Gafter, Rivka Gal, Adi Shani, Thomas Tichler, Jeremy Shapira, Israel Bruderman, Rafael Catane, Bella Kaufman, John K. Whisnant, Karl L. Mettinger, Yona Kalechman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


The immunomodulator AS101 has been demonstrated to exhibit radioprotective and chemoprotective effects in mice. Following phase-1 studies, preliminary results from phase-11 clinical trials on non-small-cell-lung-cancer patients showed a reduction in the severity of alopecia in patients treated with AS 101 in combination with chemotherapy. To further substantiate these findings, the present study was extended to include 58 patients treated either with the optimal dose of 3 mg/m2 AS 101 combined with carboplatin and VP-16, or with chemotherapy alone. As compared with patients treated with chemotherapy alone, there was a significant decrease in the level of alopecia in patients receiving the combined therapy. The newly developed rat model was used to elucidate the protective mechanism involved in this effect. We show that significant prevention of chemotherapy-induced alopecia is obtained in rats treated with Ara-C combined with AS101, administered i.p. or s.c. or applied topically to the dorsal skin. We show that this protection by AS101 is mediated by macrophage-derived factors induced by AS101. Protection by AS101 can be ascribed, at least in part, to IL-1, since treatment of rats with IL-1RA largely abrogated the protective effect of AS101. Moreover, we demonstrate that in humans there is an inverse correlation between the grade of alopecia and the increase in IL-1α. In addition, protection by AS101 could be related to PGE2 secretion, since injection of indomethacin before treatment with AS101 and Ara-C partly abrogated the protective effect of AS101. To assess the ability of AS101 to protect against chemotherapy-induced alopecia, phase-II clinical trials have been initiated with cancer patients suffering from various malignancies.

Original languageEnglish
Pages (from-to)97-103
Number of pages7
JournalInternational Journal of Cancer
Issue number1
StatePublished - 3 Jan 1996


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