Diphenylcyclopropenone for the treatment of cutaneous in‐transit melanoma metastases – results of a prospective, non‐randomized, single‐centre study

Read, Tavis; Webber, S.; Tan, Jean-Marie; Wagels, Michael; Schaider, Helmut; Soyer, H. Peter; Smithers, B. Mark

doi:10.1111/jdv.14422

Cited by 23 publications

(27 citation statements)

References 31 publications

(38 reference statements)

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“…Table summarizes the key data for each modality and presents the pooled results including the weighted ORR and meta‐analysis data. Assessed studies included: randomized controlled trials, nonrandomized phase I and II comparative and noncomparative studies, and prospective or retrospective case series (NHMRC levels II–IV evidence; Tables S2‐S9) . Only two therapies: amputation and topical imiquimod, were suitable for formal meta‐analysis ( I 2 value ≤ 40%).…”

Section: Resultsmentioning

confidence: 99%

“…Data supports the selection of patients with superficial "epidermotropic" lesion morphologies as this phenotype has experienced higher response rates. 57,58 This is logical given the topical mode of administration and the proposed mechanism of action. DPCP therapy has been consistently reported as convenient, well-tolerated and economically viable.…”

Section: Published the Results Of A Northmentioning

confidence: 99%

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A systematic review and meta‐analysis of locoregional treatments for in‐transit melanoma

Read

Lonne

Sparks

et al. 2019

Journal of Surgical Oncology

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Background and Objectives In‐transit melanoma (ITM) metastases present a therapeutic challenge and management decisions can be difficult. There are multiple treatments available, with differing efficacy, and supported by different levels of evidence. The primary objective was to perform a systematic review and where suitable, a meta‐analysis of the literature reporting on the use of locoregional treatments for the management of ITM. Methods An independent review was conducted including a comprehensive search of the National Library of Medicine using PubMed, MEDLINE, Embase, and Cochrane Library databases. Key data were tabulated, synthesized and pooled to calculate relevant weighted effect sizes for each therapy using random‐effect models. The statistical heterogeneity was calculated using the Higgins' method. Results Of the initial 32 612 articles identified, 57 original articles satisfied eligibility criteria. Eight treatment modalities were identified comprising: amputation (7); hyperthermic isolated limb perfusion (15); isolated limb infusion (8); carbon dioxide laser (9); PV‐10 intralesional therapy (5); IL‐2 intralesional therapy (8); imiquimod (7); diphenylcyclopropenone (3). Only amputation and topical imiquimod were suitable for formal meta‐analysis. Conclusions All of the assessed therapies have significant selection bias. Variable levels of evidence support the ongoing use of locoregional treatments and these may significantly improve disease‐free survival.

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Section: Resultsmentioning

confidence: 99%

Section: Published the Results Of A Northmentioning

confidence: 99%

A systematic review and meta‐analysis of locoregional treatments for in‐transit melanoma

Read

Lonne

Sparks

et al. 2019

Journal of Surgical Oncology

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“…Diphencyprone is a contact sensitizer thought to act via enhancing lymphocyte anti‐tumour activity. A single centre prospective study demonstrated a 22% CR rate for patients with cutaneous ITM and a disease‐free interval of 12.3 months . However, adverse effects including contact hypersensitivity, blistering, regional lymphadenopathy and generalized dermatitis may limit its use .…”

Section: Topical Therapiesmentioning

confidence: 99%

Management of in‐transit melanoma metastases: a review

Tie

Henderson

Gyorki

2018

ANZ Journal of Surgery

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In-transit metastases (ITM) of cutaneous melanoma are locoregional recurrences confined to the superficial lymphatics that occur in 3.4-6.2% of patients diagnosed with melanoma. ITM are a heterogeneous disease that poses a therapeutic dilemma. Patients may have a prolonged disease trajectory involving multiple or repeat treatment modalities for frequent recurrences. The management of ITM has evolved without the development of a standardized protocol. Owing to the variability of the disease course there are few dedicated clinical trials, with a number of key trials in stage III melanoma excluding ITM patients. Thus, there is a paucity of quality data on the efficacy of the treatment modalities available for ITM and even fewer studies directly comparing modalities. At present the mainstay of ITM treatment is surgical resection, with intralesional therapies, isolated limb infusion and radiotherapy utilized as second-line measures. The developing role of targeted therapies and immunotherapy has yet to be explored completely in these patients. This review addresses the evidence base of the efficacy of the various treatment modalities available and those factors that have impacted their clinical uptake.

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“…The largest published study to date was conducted in 54 patients who were prospectively treated using DPCP (0.005%‐1% aqueous cream) . Complete responses (CRs) were observed in 22% of patients, partial responses (PRs) in an additional 39% and eight patients (15%) did not respond.…”

Section: Introductionmentioning

confidence: 99%

Management of local or regional non‐nodal disease

Racz

Block

Baum

et al. 2018

Journal of Surgical Oncology

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Some melanomas develop a striking avidity for lymphatic spread. In spite of multiple recurrences, patients can remain years without visceral metastasis. There is clearly a biologic reason for this lymphotrophic pattern of growth and dissemination, which we have yet to uncover. In-transit metastases have widely diverse clinical presentations and can be a stubborn disease to cure. As a result, a host of treatments exist that should be tailored to the individual patient. K E Y W O R D S diphenylcyclopropenone, in transit, intralesional therapy, limb perfusion, melanoma, stage III, talimogene laherparepvec 1 | INTRODUCTION Non-nodal locoregional metastasis in the setting of melanoma includes microsatellites, satellites, and in-transit metastasis (ITM). This pattern of spread is primarily the result of dermal and subcutaneous intralymphatic contamination. The presence of melanoma cells within this rich lymphatic plexus can result in recurrent disease anywhere from the primary site to the regional nodal basin and rarely retrograde, distal to the primary lesion. Historically, microsatellites were defined as microscopic foci identified on pathologic analysis, adjacent or deep to the primary. Clinically detected cutaneous and/or subcutaneous locoregional metastases were arbitrarily categorized based on their proximity to the primary melanoma; satellite lesions occurring within 2 cm of the primary and ITM lesions >2 cm from the melanoma. All these disease patterns have similar prognoses and the 8th edition of The American Joint Committee on Cancer Staging System has added clarity to this issue. 1The updated edition categorizes all regional nodal and intralymphatic disease as N1-N3 disease. Additionally, number of lesions differentiates N1-N3 and the subcategories a-c are distinguished based on clinically occult, clinically detected, matted and/or intralymphatic disease. One should make a distinction, when possible, between a true local recurrence, which represents subclinical persistent primary tumor after initial management; often in the setting of inadequate management such as incomplete resection, as opposed to intralymphatic disease. A true local recurrence portends a better prognosis than cutaneous metastases. 2 The distinction between distant skin, subcutaneous or lymph node metastasis is even more important as these are categorized as M1a, stage IV disease.In-transit metastases occur in 5% to 10% of patients with intermediate thickness melanoma [3][4][5][6][7] and have a propensity for the lower extremities. 8,9 In-transit metastasis often appear indolent and easily treatable, particularly when few in number. However, due to the aforementioned concept of lymphatic contamination, recurrence remains the rule and not the exception especially when management consists of targeted treatment of individual lesions rather than a more holistic approach that addresses the involved lymphatic network and nodal basin. Before embarking on treatment of new ITM, we obtain systemic imaging, PET scan preferred, to rule out clinically ...

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Diphenylcyclopropenone for the treatment of cutaneous in‐transit melanoma metastases – results of a prospective, non‐randomized, single‐centre study

Abstract: DPCP provided a well-tolerated, convenient and efficacious treatment for cutaneous ITM metastases. Identifying patterns of response may assist treatment selection and improve patient-rated outcomes.

Cited by 23 publications

References 31 publications

A systematic review and meta‐analysis of locoregional treatments for in‐transit melanoma

A systematic review and meta‐analysis of locoregional treatments for in‐transit melanoma

Management of in‐transit melanoma metastases: a review

Management of local or regional non‐nodal disease

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