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Advances in dermatology and venereology Acta Dermato-Venereologica
Topical Carmustine as Monotherapy or as Multimodality Therapy for Folliculotropic Mycosis Fungoides
Kelly M . MACARTHUR 1 , Neha JARIWALA 2 , Ellen J . KIM 3 and Alain H . ROOK 3
1
Department of Dermatology , Johns Hopkins University , 601 North Caroline Street , 8 th Floor , Baltimore , Maryland , 21287 , 2 Drexel University School of Medicine , Philadelphia , PA , and 3 Department of Dermatology , Perelman School of Medicine , University of Pennsylvania , Philadelphia , PA , USA . E-mail : kmacart1 @ jhmi . edu Accepted Oct 12 , 2016 ; Epub ahead of print Oct 14 , 2016
Folliculotropic mycosis fungoides ( MF ) is a rare variant of cutaneous T-cell lymphoma with distinct clinical and histological features that is less responsive to therapy than the classic epidermotropic subtype of MF ( 1 , 2 ). At any given stage , the folliculotropic variant has a worse prognosis than the epidermotropic variant . Due to the ( peri ) follicular nature of the neoplastic cells in folliculotropic MF , the T-cell infiltrate is thought to be too deep for penetration of many skin-directed treatments . Topical monotherapy is not currently recommended in the current National Comprehensive Cancer Network ( NCCN ) ( 3 ) guidelines as a mainstay treatment option even in patients with a low burden of disease . There is limited evidence that carmustine topical therapy ( also known as bis-chlorethylnitrosourea or BCNU ) may be beneficial in the treatment of folliculotropic MF . In this study , we hypothesized that topical carmustine would be a safe and effective treatment option for patients with stages I – III folliculotropic MF .
METHODS
Thirteen consecutive patients with biopsy-proven , folliculotropic MF ( stages IA through IIIB ) treated with topical carmustine between 2009 and 2016 in the Cutaneous Lymphoma Clinic at the University of Pennsylvania were included ( Figs 1 and S1 1 ). Review of the patients ’ records was approved by the University of Pennsylvania Institutional Review Board . Median age at diagnosis was 60 years ( 32 – 80 years ). Twelve of the 13 patients were men . At diagnosis , patients were noted to have the following disease stages : IA ( n = 1 ), IB ( n = 8 ), IIB ( n = 2 ), IIIA ( n = 1 ), and IIIB ( n = 1 ) with a median time from diagnosis to initiation of carmustine of 22 months ( 0 – 144 months ). At the time receiving carmustine , 4 patients were treatment-naïve and 9 patients had disease that was refractory to prior monotherapy or multimodality therapy ( Table SI 1 ). All 13 patients were treated with carmustine topical therapy as formerly published under the NCCN ( 3 ) guidelines following a thorough discussion of the risks and benefits of treatment . Patients were instructed to apply topical carmustine 0.04 % ointment to all affected areas . In 9 cases , patients were treated with topical carmustine plus another systemic agent , including low-dose interferon ( IFN ) -α or γ at 1 – 2 million units 3 times weekly or low-dose isotretinoin at 10 – 20 mg daily , while the remaining 4 patients were treated with topical carmustine as monotherapy .
The primary endpoint was global response based upon physical examination of skin and nodes and peripheral blood assessment . Partial response ( PR ) was defined as 50 % or greater improvement in involvement . Complete response ( CR ) was defined as full resolution of lesions on physical examination with no residual visible changes of follicular plugging or active skin lesions . Post-treatment biopsy was not routinely performed . Toxicities were scored using CTCAEv4.0 ( Common Terminology Criteria for Adverse Events version 4.0 ).
RESULTS
Fig . 1 . Folliculotropic mycosis fungoides ( MF ). A ) Neck of patient 11 with folliculotropic MF refractory to topical Nitrogen mustard therapy prior to treatment with topical carmustine and B ) after 4 months of treatment with topical carmustine .
Median treatment duration with carmustine was 12 months ( 3 – 56 months ) in this cohort of 13 patients . Median follow-up was 12 months ( 3 – 56 months ). Median time to achieve response ( either PR or CR ) was 4 months ( 2 – 8 months ).
Nine patients in the study proved to have prior treatment-refractory disease ( 7 with stage IB , one with IIB , one with IIIB disease ), see Table SI 1 . Topical carmustine was used as monotherapy or combined with other treatments at the discretion of the treating physician based on the clinical presentation and the clinician ’ s expert judgment . Typically , if patients presented with progression of disease while receiving other systemic therapies , topical carmustine was started and a multimodality approach was pursued , often using IFNγ . For the 9 patients with previous treatment-refractory disease , all were alive at last follow-up ; 5 achieved a CR , and 4 achieved PR ( Table SI 1 ) at last follow-up . The 4 patients with PR demonstrated ongoing clinical improvement at the time of last follow-up on continued topical carmustine therapy .
For the 4 patients with treatmentnaïve disease , stage at diagnosis included : IA ( n = 1 ), IB ( n = 1 ), IIB ( n = 1 ) and IIIA ( n = 1 ). Two patients were treated with topical carmustine monotherapy , and two patients were treated with topical carmustine with concomitant systemic IFNα ( Table SI 1 ). The treatment decision for monotherapy versus dual therapy was based on the patient ’ s
This is an open access article under the CC BY-NC license . www . medicaljournals . se / acta Journal Compilation © 2017 Acta Dermato-Venereologica . doi : 10.2340 / 00015555-2551 Acta Derm Venereol 2017 ; 97 : 373 – 374