Topical chemotherapy in cutaneous T-cell lymphoma: positive results of a randomized, controlled, multicenter trial testing the efficacy and safety of a novel mechlorethamine, 0.02%, gel in mycosis fungoides.
OBJECTIVE
To evaluate the efficacy and safety of a novel mechlorethamine hydrochloride, 0.02%, gel in mycosis fungoides. DESIGN Randomized, controlled, observer-blinded, multicenter trial comparing mechlorethamine, 0.02%, gel with mechlorethamine, 0.02%, compounded ointment. Mechlorethamine was applied once daily for up to 12 months. Tumor response and adverse events were assessed every month between months 1 and 6 and every 2 months between months 7 and 12. Serum drug levels were evaluated in a subset of patients.


METHODS
Academic medical or cancer centers.


METHODS
In total, 260 patients with stage IA to IIA mycosis fungoides who had not used topical mechlorethamine within 2 years and were naive to prior use of topical carmustine therapy.


METHODS
Response rates of all the patients based on a primary clinical end point (Composite Assessment of Index Lesion Severity) and secondary clinical end points (Modified Severity-Weighted Assessment Tool and time-to-response analyses).


RESULTS
Response rates for mechlorethamine gel vs ointment were 58.5% vs 47.7% by the Composite Assessment of Index Lesion Severity and 46.9% vs 46.2% by the Modified Severity-Weighted Assessment Tool. By the Composite Assessment of Index Lesion Severity, the ratio of gel response rate to ointment response rate was 1.23 (95% CI, 0.97-1.55), which met the prespecified criterion for noninferiority. Time-to-response analyses demonstrated superiority of mechlorethamine gel to ointment (P< .01). No drug-related serious adverse events were seen. Approximately 20.3% of enrolled patients in the gel treatment arm and 17.3% of enrolled patients in the ointment treatment arm withdrew because of drug-related skin irritation. No systemic absorption of the study medication was detected.


CONCLUSIONS
The use of a novel mechlorethamine, 0.02%, gel in the treatment of patients with mycosis fungoides is effective and safe.


BACKGROUND
clinicaltrials.gov Identifier:NCT00168064.
Division of Dermatology, Department of Pathology, Fox Chase Cancer Center, University of Pennsylvania, Philadelphia, USA. drlessin@brynmawrskinandcancer.com
Stuart R
SR
Lessin
Madeleine
M
Duvic
Joan
J
Guitart
Amit G
AG
Pandya
Bruce E
BE
Strober
Elise A
EA
Olsen
Christopher M
CM
Hull
Elizabeth H
EH
Knobler
Alain H
AH
Rook
Ellen J
EJ
Kim
Mark F
MF
Naylor
David M
DM
Adelson
Alexa B
AB
Kimball
Gary S
GS
Wood
Uma
U
Sundram
Hong
H
Wu
Youn H
YH
Kim
D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005782:Gels; D006801:Humans; D008297:Male; D008466:Mechlorethamine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D009824:Ointments; D012720:Severity of Illness Index; D016037:Single-Blind Method; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D018906:Antineoplastic Agents, Alkylating; D005782:Gels; D009824:Ointments; D008466:Mechlorethamine