A phase I trial of topical topitriol (calcitriol, 1,25-dihydroxyvitamin D3) to prevent chemotherapy-induced alopecia.
This study evaluated the toxicity and efficacy of topical topitriol (calcitriol, 1,25-dihydroxyvitamin D3) to prevent chemotherapy-induced alopecia (CIA). Patients with breast cancer scheduled to receive FAC chemotherapy (5-fluorouracil, adriamycin and cyclophosphamide) were eligible for the study. Initially, the first six patients were randomized in a double-blind fashion to have received topitriol or placebo with all subsequent patients being treated with topitriol. Topitriol cream (0.0025 or 0.005%; 25 and 50 microg/g concentration) was administered topically twice a day. Three different doses and schedules of administration were evaluated including: 500 and 1000 microg daily for 7 days prior to chemotherapy, and 2000 microg daily for 5 days prior and 5 days post-chemotherapy. Fourteen patients were treated (12 with topitriol and two with placebo) at three different dose levels. All patients developed grade 2 alopecia between day 20 and 30 after chemotherapy, demonstrating the lack of efficacy of topical topitriol on this schedule of administration to prevent CIA. Eight patients exposed to topitriol developed a toxic maculopapular dermatitis in areas exposed to the drug. In conclusion, topical topitriol at the doses and schedules evaluated in this trial was ineffective to prevent CIA and induced a local dermatitis in areas exposed to the drug.
Hidalgo
M
M
Institute for Drug Development, Cancer Therapy and Research Center, University of Texas Health Science Center, San Antonio 78229, USA. mhildago@saci.org
Rinaldi
D
D
Medina
G
G
Griffin
T
T
Turner
J
J
Von Hoff
D D
DD
D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000505:Alopecia / Q000139:chemically induced / Q000517:prevention & control*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018567:Breast Neoplasms, Male / Q000188:drug therapy* / Q000473:pathology; D002117:Calcitriol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging
D003879:Dermatologic Agents; D004317:Doxorubicin; D003520:Cyclophosphamide; D002117:Calcitriol; D005472:Fluorouracil