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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