Relationship between irreversible alopecia and exposure to cyclophosphamide, thiotepa and carboplatin (CTC) in high-dose chemotherapy.

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Bone Marrow Transplant 2002 Nov;30(9):593-7

Relationship between irreversible alopecia and exposure to cyclophosphamide, thiotepa and carboplatin (CTC) in high-dose chemotherapy.

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.

Eur J Endocrinol 2002 Sep;147(3):357-61

An endocrinopathy characterized by dysfunction of the pituitary-adrenal axis and alopecia universalis: supporting the entity of a triple H syndrome.

We demonstrate the rare disorder of triple H syndrome in a 25-year-old man. He was pointed out as having short stature, at -5.9 s.d., and diagnosed as GH deficient at 6 years old. Approximately a year ago, he noticed systematic hair loss. He lost body weight by 7 kg during the last half year. He was admitted to Jichi Medical School Hospital because of unconsciousness. Physical findings showed disturbance of consciousness with Japan Coma Scale I-3. He had emaciation and alopecia universalis. Laboratory findings showed plasma glucose was as low as 1.11 mmol/l. GH and ACTH deficiency with hypoadrenocorticism were clarified. His intelligence was in the low normal range with a WAIS IQ of 70, and anterograde amnesia was suggested in the presence of a little, but not significant, morphological change in the hippocampus on a magnetic resonance imaging scan. Replacement by a physiological dose of hydrocortisone normalized plasma glucose, and restored body weight and growth of hair during the 7 month therapeutic period. The present finding strongly supports a clinical entity of triple H syndrome, including ACTH deficiency, alopecia universalis and anterograde amnesia, and that there may be some variation of the triad among the subjects.

Br J Dermatol 2002 Jun;146(6):992-9

Effects of minoxidil 2% vs. cyproterone acetate treatment on female androgenetic alopecia: a controlled, 12-month randomized trial.

BACKGROUND: Hormone studies have demonstrated the androgen-dependent character of female androgenetic alopecia, but there have been few controlled studies of therapies for alopecia in women. OBJECTIVES: To compare topical minoxidil 2% and cyproterone acetate in the treatment of female alopecia. METHODS: Sixty-six women with female-pattern alopecia were randomly assigned for 12 cycles into two groups, 33 received two local applications (2 mL day-1) of topical minoxidil 2% plus combined oral contraceptive and 33 received cyproterone acetate 52 mg day-1 plus ethinyl oestradiol 35 microg for 20 of every 28 days. RESULTS: A mean reduction of 2.4 +/- 6.2 per 0.36 cm2 in hairs of diameter > 40 microm was observed in the cyproterone acetate group (P = 0.05) and a mean increase of 6.5 +/- 9 per 0.36 cm2 in the minoxidil group (P < 0.001). Comparison of the total number of hairs at 12 months and the body mass index (BMI) revealed a borderline positive correlation in the cyproterone acetate group (r = 0.39, P = 0.06) and a negative correlation in the minoxidil group (r = -0.42, P < 0.05). No significant difference was observed in the total number of hairs among cyproterone acetate patients according to the presence or absence of other symptoms of hyperandrogenism, whereas in the minoxidil group, the total number of new hairs was higher in patients with isolated alopecia (Delta = 8.1; P < 0.05). Variations in scalp seborrhoea were significant in both groups, but the result was better (for acne and hirsutism as well) in the cyproterone acetate group than in the minoxidil group (P < 0.001). CONCLUSIONS: Minoxidil treatment was more effective in the absence of other signs of hyperandrogenism, hyperseborrhoea, and menstrual cycle modifications when the BMI was low, and when nothing argued in favour of biochemical hyperandrogenism. Cyproterone acetate treatment was more effective when other signs were present and when the BMI was elevated, factors that favoured a diagnosis of biochemical hyperandrogenism.

Oncology 2002;62(2):97-102

Effectiveness of the MSC cold cap system in the prevention of chemotherapy-induced alopecia.

OBJECTIVE: To study the effectiveness of the MSC cold cap system to prevent chemotherapy-induced alopecia. METHODS: The system was applied in 83 cancer patients (mean age 49.8 years) undergoing chemotherapy with alopecia-causing agents. Seven patients did not tolerate the system. Seventy-six patients were evaluable for assessment; 26 received anthracycline (group A), 33 taxane (group T), 5 anthracycline plus taxane (group AT), 7 intravenous etoposide (group E) and 5 ifosfamide with or without other alopecia-causing drugs (group I). In group A, 18 patients received conventional (subgroup Ac) and 8 high doses (subgroup Ah). In group T, 8 patients received docetaxel (subgroup D) and 25 paclitaxel (subgroup P). Alopecia grade 0-1 (Dean's system) was considered as treatment success. RESULTS: Grade 0-1 alopecia was achieved in 49/76 (64.5%) patients: group T 23/33 (69.6%), subgroup P 16/25 (64%) and subgroup D 7/8 (87.5%); group A 18/26 (69.2%), subgroup Ac 16/18 (88.8%) and subgroup Ah 2/8 (25%); group AT 1/5 (20%); group E 6/7 (85.7%), and group I 1/5 (20%). CONCLUSIONS: The MSC cold cap system is effective in preventing alopecia from anthracycline, etoposide or taxane but not from anthracycline-taxane combinations or ifosfamide-containing regimens.

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