Reversible
alopecia is a commonly observed, important and distressing complication of
chemotherapy. Permanent
alopecia, however, is rare after standard-dose
therapy, but has occasionally been observed after high-dose
chemotherapy with
cyclophosphamide,
thiotepa and
carboplatin (CTC). We evaluated the relationships between total exposure to these three compounds and their different metabolites in the high-dose
CTC regimen, and the subsequent development of irreversible
alopecia. Twenty-four patients received two or three courses of high-dose CTC, each followed by peripheral blood progenitor cell
transplantation. Plasma levels of
cyclophosphamide, its active metabolite
4-hydroxycyclophosphamide,
thiotepa, its active metabolite
tepa, and
carboplatin were determined, and the area-under-the-plasma concentration-versus-time curves (AUC) of the compounds were calculated. Eight of the 24 patients included in the study developed permanent
alopecia, while seven had normal hair regrowth and nine patients developed incomplete and/or thin hair regrowth. The
carboplatin AUC and the summed AUC of
thiotepa and
tepa were both significantly associated with increasing irreversibility of
hair loss. These results suggest that high exposure to
carboplatin and the sum of the
thiotepa and
tepa exposure may lead to the development of permanent
alopecia. This knowledge could guide therapeutic
drug monitoring in order to prevent the occurrence of permanent
alopecia and thereby improve the patients' quality of life.