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1
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Yourdkhani A, Esfandyari-Manesh M, Ranjbaran P, Amani M, Dinarvand R. Recent progress in topical and transdermal approaches for melanoma treatment. Drug Deliv Transl Res 2025; 15:1457-1495. [PMID: 39653958 DOI: 10.1007/s13346-024-01738-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/27/2024] [Indexed: 04/04/2025]
Abstract
The global incidence of melanoma, the most lethal form of skin cancer, continues to escalate, emphasizing the urgent need for more effective therapeutic strategies. This review assesses the latest advancements in topical and transdermal drug delivery systems, positioning them as promising alternatives. These systems allow for the direct application of therapeutic agents to tumor sites, enhancing drug effectiveness, improving patient compliance, and reducing systemic toxicity. Specifically, innovations such as nanoparticles, microneedles, and vesicular systems are explored for their potential to optimize topical and localized drug delivery. By incorporating a graphical overview of these drug delivery vehicles, we visually underscore their roles in enhancing therapeutic outcomes across various treatment categories such as chemotherapy, immunotherapy, phototherapy, phytotherapy, and targeted therapy. This article critically evaluates recent breakthroughs, addresses the current challenges faced by researchers, and explores the future directions of topical and transdermal approaches in melanoma management. By presenting a summary of the latest research and predicting future trends, this review aims to inform ongoing developments and encourage further innovation in strategies for treating melanoma.
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Affiliation(s)
- Alaleh Yourdkhani
- Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Mehdi Esfandyari-Manesh
- Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
| | - Paniz Ranjbaran
- Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahdiyar Amani
- Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Rassoul Dinarvand
- Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
- Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
- Leicester School of Pharmacy, De Montfort University, Leicester, UK.
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2
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Jin S, He Z, Du Y, Jin G, Wang K, Yang F, Zhang J. An overview of cyclopropenone derivatives as promising bioactive molecules. Bioorg Med Chem Lett 2024; 109:129845. [PMID: 38852789 DOI: 10.1016/j.bmcl.2024.129845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Revised: 05/28/2024] [Accepted: 06/06/2024] [Indexed: 06/11/2024]
Abstract
Cyclopropenone is a valuable electrophilic reagent that can react with electrophilic reagents, nucleophilic reagents, free radicals, organic metals, etc. Furthermore, cyclopropenone derivatives have shown significant biological activity in various diseases, such as triple-negative breast cancer (TNBC), melanoma, and alopecia areata (AA). The cyclopropenone analogue diphenylcyclopropenone (DPCP) has been approved for the treatment of AA. Given the potential therapeutic benefits of cyclopropenone derivatives, this review aims to systematically summarize the structures, synthesis routes, and potential pharmacological functions of cyclopropenone analogues in the hope of offering novel insights for further rational design of more drugs based on the cyclopropenone skeleton for the treatment of human diseases.
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Affiliation(s)
- Sasa Jin
- Pharmacy College, Henan University of Chinese Medicine, 450046 Zhengzhou, PR China
| | - Zhangxu He
- Pharmacy College, Henan University of Chinese Medicine, 450046 Zhengzhou, PR China.
| | - Yuanbing Du
- Pharmacy College, Henan University of Chinese Medicine, 450046 Zhengzhou, PR China
| | - Gang Jin
- Pharmacy College, Henan University of Chinese Medicine, 450046 Zhengzhou, PR China
| | - Kaiyue Wang
- Pharmacy College, Henan University of Chinese Medicine, 450046 Zhengzhou, PR China
| | - Feifei Yang
- Pharmacy College, Henan University of Chinese Medicine, 450046 Zhengzhou, PR China.
| | - Jingyu Zhang
- Pharmacy College, Henan University of Chinese Medicine, 450046 Zhengzhou, PR China.
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3
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Pham JP, Dwyer L, Phan K, Menzies AM, Frew JW. Efficacy of topical diphencyprone for melanoma in-transit metastases: a systematic review and meta-analysis. Melanoma Res 2023; 33:434-436. [PMID: 37650727 DOI: 10.1097/cmr.0000000000000914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
Affiliation(s)
- James P Pham
- Department of Dermatology, Liverpool Hospital
- School of Clinical Medicine, UNSW Medicine and Health, Sydney
- Laboratory of Translational Cutaneous Medicine, Ingham Institute of Applied Medical Research, Liverpool
| | - Liam Dwyer
- School of Clinical Medicine, UNSW Medicine and Health, Sydney
- Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown
| | - Kevin Phan
- Department of Dermatology, Liverpool Hospital
| | - Alexander M Menzies
- Melanoma Institute Australia, The University of Sydney
- Faculty of Medicine and Health, The University of Sydney
- Department of Medical Oncology, Royal North Shore and Mater Hospitals, Sydney, New South Wales, Australia
| | - John W Frew
- Department of Dermatology, Liverpool Hospital
- School of Clinical Medicine, UNSW Medicine and Health, Sydney
- Laboratory of Translational Cutaneous Medicine, Ingham Institute of Applied Medical Research, Liverpool
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4
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Halim HM, Ahmed SFAE, Eyada MM. Effectiveness and safety of topical application of diphenylcyclopropenone versus podophyllin in treatment of genital warts. Int J STD AIDS 2023:9564624231169330. [PMID: 37018551 DOI: 10.1177/09564624231169330] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/07/2023]
Abstract
BACKGROUND Many therapeutic modalities are available for treating genital warts; however, the effectiveness of both diphenylcyclopropenone and podophyllin is still controversial. AIM To evaluate the effectiveness and safety of diphenylcyclopropenone and podophyllin in treating genital warts. METHODS This study included 57 patients, divided randomly into two groups. Group (A): diphenylcyclopropenone (n = 29). Group (B): podophyllin 25% (n = 28). In group (A), sensitization was done with 2% diphenylcyclopropenone. Then, after 1 or 2 weeks, treatment started with a weekly application of diphenylcyclopropenone solutions ranging between 0.001 and 1% until clearance, or for a maximum of 10 sessions. In group (B), podophyllin 25% was applied weekly until clearance or for a maximum of 6 weeks. RESULTS Higher clearance was achieved in group A, with 19 of 29 (65.5%) patients, than in group B, with 9 of 28 (32.1%) (p-value = 0.004). Also, effectiveness increases with young age in group A. Shorter wart duration was associated with better response in both groups (p-value = 0.005). No serious adverse effects occurred in either group. No recurrence was detected in group A, while seven patients (77.8%) had recurrence in group B after 1 year of follow up. CONCLUSION Diphenylcyclopropenone shows a higher success rate than podophyllin in treating genital warts and a lower recurrence rate.
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Affiliation(s)
- Halim Maher Halim
- Department of Dermatology, Venereology and Andrology, Faculty of Medicine, 68833Suez Canal University, Ismailia, Egypt
| | | | - Moustafa Mk Eyada
- Department of Dermatology, Venereology and Andrology, Faculty of Medicine, 68833Suez Canal University, Ismailia, Egypt
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5
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Use of Contact Immunotherapy in the Treatment of Skin Diseases Other than Alopecia Areata. Dermatol Ther (Heidelb) 2022; 12:2415-2452. [PMID: 36136235 DOI: 10.1007/s13555-022-00818-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Accepted: 09/13/2022] [Indexed: 11/03/2022] Open
Abstract
For decades, contact immunotherapy with dinitrochlorobenzene, diphencyprone, and squaric acid dibutylester has played an important role in both clinical practice and scientific research. It is listed as the first-line treatment for extensive alopecia areata and was more recently approved for melanoma treatment as an orphan drug in the USA. Moreover, owing to the relative low cost and safety, topical immunotherapy has also been used in many infectious, neoplastic, and inflammatory dermatological diseases. It is especially valuable in vulnerable groups, for cosmetic/pain sensitive areas, or for multiple lesions. In this review, we summarize the current evidence supporting the use of contact immunotherapy for treatment of skin diseases, from articles collected from PubMed database. Owing to space limitation and already numerous studies focusing on alopecia areata, we include only skin diseases other than alopecia areata. In addition to diseases that have been reported to be treated by contact immunotherapy, the hypothesized mechanism, prognosis prediction, efficacy, and safety of these topical agents are discussed.
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6
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Ronel T, Harries M, Wicks K, Oakes T, Singleton H, Dearman R, Maxwell G, Chain B. The clonal structure and dynamics of the human T cell response to an organic chemical hapten. eLife 2021; 10:54747. [PMID: 33432924 PMCID: PMC7880692 DOI: 10.7554/elife.54747] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Accepted: 01/12/2021] [Indexed: 12/27/2022] Open
Abstract
Diphenylcyclopropenone (DPC) is an organic chemical hapten which induces allergic contact dermatitis and is used in the treatment of warts, melanoma, and alopecia areata. This therapeutic setting therefore provided an opportunity to study T cell receptor (TCR) repertoire changes in response to hapten sensitization in humans. Repeated exposure to DPC induced highly dynamic transient expansions of a polyclonal diverse T cell population. The number of TCRs expanded early after sensitization varies between individuals and predicts the magnitude of the allergic reaction. The expanded TCRs show preferential TCR V and J gene usage and consist of clusters of TCRs with similar sequences, two characteristic features of antigen-driven responses. The expanded TCRs share subtle sequence motifs that can be captured using a dynamic Bayesian network. These observations suggest the response to DPC is mediated by a polyclonal population of T cells recognizing a small number of dominant antigens.
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Affiliation(s)
- Tahel Ronel
- Division of Infection and Immunity, University College London, London, United Kingdom.,Cancer Institute, University College London, London, United Kingdom
| | - Matthew Harries
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.,Salford Royal NHS Foundation Trust (Dermatology Centre), Salford, United Kingdom
| | - Kate Wicks
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
| | - Theres Oakes
- Division of Infection and Immunity, University College London, London, United Kingdom
| | - Helen Singleton
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
| | - Rebecca Dearman
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
| | - Gavin Maxwell
- Safety and Environmental Assurance Centre, Unilever, Colworth Science Park, Bedford, United Kingdom
| | - Benny Chain
- Division of Infection and Immunity, University College London, London, United Kingdom.,Department of Computer Science, University College London, London, United Kingdom
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7
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Haywood S, Garioch J, Ramaiya A, Moncrieff M. Quantitative and Spatial Analysis of CD8+/PD-1 Tumor-Infiltrating Lymphocytes as a Predictive Biomarker for Clinical Response of Melanoma In-Transit Metastases to Topical Immunotherapy. Ann Surg Oncol 2020; 28:1029-1038. [PMID: 32542563 PMCID: PMC7801318 DOI: 10.1245/s10434-020-08713-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Indexed: 12/21/2022]
Abstract
Background Melanoma in-transit metastases (ITMs) are a challenge to treat and associated with systemic disease and poor prognosis. Topical diphencyprone (DPCP), a potent contact sensitizer, is an established treatment for melanoma ITMs. This exploratory study investigated the utility of BRAF mutation status, CD8, PD-1, PD-L1, and TILs distribution as biomarkers for response of ITMs to topical immunotherapy (DPCP). Methods The ITM deposits of 40 patients treated with DPCP were subjected to biomarker analysis for BRAF status, CD8 and PD-1 expression on tumor-infiltrating lymphocytes (TILs), and tumor PD-L1 expression. Response to DPCP and overall survival (OS) were compared by biomarker status. Results After 12 weeks, 10 patients (25%) had a complete response, 12 patients (30%) had a partial response, and 18 patients (45%) had no response. No significant association was found between any individual biomarker and response to DPCP or OS. The BRAF mutation rate was 25% (10/40). All the patients with a complete response had BRAF wild-type tumor. Peritumoral CD8+ T-cells were associated with complete response (P = 0.041). Both CD8+ and PD-1 expressions were highly correlated (P < 0.0001), and the highest levels of PD-1 expression were detected at the peritumoral interface (P = 0.0004). Only two cases were PD-L1-positive, and both had a complete response to DPCP (P = 0.043). Conclusion Patients who have BRAF wild-type tumor are more likely to experience a complete response to DPCP. Peritumoral TILs and PD-1 expressions may predict a better response to DPCP. Expression of PD-L1 may be associated with a complete response to DPCP. A larger prospective study is required.
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Affiliation(s)
- Sophia Haywood
- Norwich Medical School, University of East Anglia, Norwich, UK
| | - Jennifer Garioch
- Norwich Medical School, University of East Anglia, Norwich, UK.,Department of Dermatology, Norfolk and Norwich University Hospital, Norwich, UK
| | - Arjun Ramaiya
- Norwich Medical School, University of East Anglia, Norwich, UK.,Cotman Centre of Cellular Pathology, Norwich Research Park, Norfolk and Norwich University Hospital, Norwich, UK
| | - Marc Moncrieff
- Norwich Medical School, University of East Anglia, Norwich, UK. .,Department of Plastic and Reconstructive Surgery, Norfolk and Norwich University Hospital, Norwich, UK.
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8
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Wright FC, Kellett S, Hong NJL, Sun AY, Hanna TP, Nessim C, Giacomantonio CA, Temple-Oberle CF, Song X, Petrella TM. Locoregional management of in-transit metastasis in melanoma: an Ontario Health (Cancer Care Ontario) clinical practice guideline. Curr Oncol 2020; 27:e318-e325. [PMID: 32669939 PMCID: PMC7339852 DOI: 10.3747/co.27.6523] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Objective The purpose of this guideline is to provide guidance on appropriate management of satellite and in-transit metastasis (itm) from melanoma. Methods The guideline was developed by the Program in Evidence-Based Care (pebc) of Ontario Health (Cancer Care Ontario) and the Melanoma Disease Site Group. Recommendations were drafted by a Working Group based on a systematic review of publications in the medline and embase databases. The document underwent patient- and caregiver-specific consultation and was circulated to the Melanoma Disease Site Group and the pebc Report Approval Panel for internal review; the revised document underwent external review. Recommendations "Minimal itm" is defined as lesions in a location with limited spread (generally 1-4 lesions); the lesions are generally superficial, often clustered together, and surgically resectable. "Moderate itm" is defined as more than 5 lesions covering a wider area, or the rapid development (within weeks) of new in-transit lesions. "Maximal itm" is defined as large-volume disease with multiple (>15-20) 2-3 cm nodules or subcutaneous or deeper lesions over a wide area.■ In patients presenting with minimal itm, complete surgical excision with negative pathologic margins is recommended. In addition to complete surgical resection, adjuvant treatment may be considered.■ In patients presenting with moderate unresectable itm, consider using this approach for localized treatment: intralesional interleukin 2 or talimogene laherparepvec as 1st choice, topical diphenylcyclopropenone as 2nd choice, or radiation therapy as 3rd choice. Evidence is insufficient to recommend intralesional bacille Calmette- Guérin or CO2 laser ablation outside of a research setting.■ In patients presenting with maximal itm confined to an extremity, isolated limb perfusion, isolated limb infusion, or systemic therapy may be considered. In extremely select cases, amputation could be considered as a final option in patients without systemic disease after discussion at a multidisciplinary case conference.■ In cases in which local, regional, or surgical treatments for itm might be ineffective or unable to be performed, or if a patient has systemic metastases at the same time, systemic therapy may be considered.
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Affiliation(s)
- F C Wright
- Department of General Surgery, Sunnybrook Health Sciences Centre/Odette Regional Cancer Centre, Toronto, ON
| | - S Kellett
- Program in Evidence-Based Care, Ontario Health (Cancer Care Ontario), and Department of Oncology, McMaster University, Hamilton, ON
| | - N J Look Hong
- Department of General Surgery, Division of Surgical Oncology, Sunnybrook Health Sciences Centre, and Department of Surgery, University of Toronto, Toronto, ON
| | - A Y Sun
- Department of Radiation Oncology, University Health Network, Princess Margaret Cancer Centre, Toronto, ON
| | - T P Hanna
- Department of Oncology, Division of Radiation Oncology, Queen's University, Kingston, ON
| | - C Nessim
- Division of General Surgery, The Ottawa Hospital, and Department of Surgery, University of Ottawa, Ottawa, ON
| | - C A Giacomantonio
- Queen Elizabeth II Health Sciences Centre, Capital District Health, and Departments of Surgery and Pathology, Dalhousie University, Halifax, NS
| | - C F Temple-Oberle
- Departments of Oncology and Surgery, University of Calgary, Calgary, AB
| | - X Song
- Department of Internal Medicine, Division of Medical Oncology, University of Ottawa, and The Ottawa Hospital Cancer Centre, Ottawa, ON
| | - T M Petrella
- Division of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, and University of Toronto, Toronto, ON
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9
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Lôbo MDM, Calsavara VF, Ricci BV, Lopes Pinto CA, Bertolli E, Duprat Neto JP. Response rates of cutaneous melanoma metastases to diphencyprone: A meta-analysis. J Am Acad Dermatol 2020; 83:1812-1813. [PMID: 32289400 DOI: 10.1016/j.jaad.2020.04.023] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2020] [Revised: 03/31/2020] [Accepted: 04/02/2020] [Indexed: 10/24/2022]
Affiliation(s)
- Matheus de Melo Lôbo
- Surgical Oncology Residence Program, A.C. Camargo Cancer Center, São Paulo, SP, Brazil
| | | | - Bruno Vita Ricci
- Surgical Oncology Residence Program, A.C. Camargo Cancer Center, São Paulo, SP, Brazil
| | | | - Eduardo Bertolli
- Skin Cancer Department, A.C. Camargo Cancer Center, São Paulo, SP, Brazil.
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10
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Lo MC, Garioch J, Moncrieff MD. Sequencing in management of in-transit melanoma metastasis: Diphencyprone versus isolate limb infusion. J Plast Reconstr Aesthet Surg 2020; 73:1263-1267. [PMID: 32245735 DOI: 10.1016/j.bjps.2020.03.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 02/02/2020] [Accepted: 03/01/2020] [Indexed: 11/29/2022]
Abstract
BACKGROUND In-transit metastases (ITMs) in melanoma are associated with poor prognosis, however a significant proportion of these patients survive for extended periods without further disease progression. We routinely use locoregional treatment e.g. Diphencyprone (DPCP) and/or isolated limb infusion (ILI) as long-term palliation. This study aimed to identify correct sequencing of these therapies based on disease burden and progression. METHOD Retrospective evaluation of all melanoma patients with ITMs treated with DPCP/ILI/both from 2010 to 2017 at our Cancer Centre was performed. Patients were initially assessed in a multidisciplinary setting and empirically prescribed DPCP for low-disease burden, ILI for high-disease burden. Patient demographics, tumour characteristics, response to therapy, ITM progression and patient outcomes were analysed. RESULTS 78 patients (M:F = 30:48), aged 47-95years (median 74years) treated with DPCP/ILI/both (n = 44/21/13) were identified. Progression-free survival (PFS) was significantly increased in patients responsive to DPCP or ILI as initial treatment. Patients who failed on DPCP and subsequently treated with ILI had a significantly increased PFS compared to DPCP alone (p = 0.026, HR = 0.048). This was not the case with patients who were treated with DPCP following failed ILI. All patients who failed to respond to the initial therapy progressed within 6 months. CONCLUSION Our study shows that careful stratification ITM patients according to disease burden is fundamental to optimal outcomes. High-disease burden patients benefit from initial ILI; low-disease burden patients should commence on DPCP. ILI can be considered in DPCP patients who fail early. Systemic therapy should be considered when locoregional therapies fail after 12 months or after rapid relapse following ILI.
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Affiliation(s)
- Michelle Ci Lo
- Plastic & Reconstructive Surgery Department, Norfolk & Norwich University Hospital, Colney Lane, Norwich NR4 7UY, UK.
| | - Jennifer Garioch
- Dermatology Department, Norfolk & Norwich University Hospital, Norwich, UK; Norwich Medical School, University of East Anglia, Norwich, UK
| | - Marc Ds Moncrieff
- Plastic & Reconstructive Surgery Department, Norfolk & Norwich University Hospital, Colney Lane, Norwich NR4 7UY, UK; Norwich Medical School, University of East Anglia, Norwich, UK
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11
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Beasley GM, Zager JS, Thompson JF. The Landmark Series: Regional Therapy of Recurrent Cutaneous Melanoma. Ann Surg Oncol 2020; 27:35-42. [PMID: 31471842 DOI: 10.1245/s10434-019-07760-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Indexed: 01/20/2023]
Abstract
In-transit melanoma represents a distinct disease pattern in which melanoma recurs as dermal or subcutaneous nodules between the primary melanoma site and the draining regional lymph node basin. The disease pattern is often not amenable to complete surgical resection. Since the 1950s, regional therapies have been explored for the treatment of this disease entity, with the goal of maximizing delivery of the therapeutic agent to the tumor while minimizing systemic toxicity. We reviewed landmark studies describing and evaluating regional chemotherapy and intralesional therapies for patients with in-transit melanoma metastases.
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Affiliation(s)
- Georgia M Beasley
- Department of Surgery, Duke University, Durham, NC, USA.
- Duke University Medical Center, Durham, NC, USA.
| | - Jonathan S Zager
- Department of Cutaneous Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA
- Department of Surgery, University of South Florida Morsani School of Medicine, Tampa, FL, USA
| | - John F Thompson
- Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia
- Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
- Discipline of Surgery, The University of Sydney, Sydney, NSW, Australia
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12
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Read RL, Thompson JF. Managing in-transit melanoma metastases in the new era of effective systemic therapies for melanoma. Expert Rev Clin Pharmacol 2019; 12:1107-1119. [DOI: 10.1080/17512433.2019.1689121] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Rebecca L Read
- Melanoma Institute Australia, The University of Sydney, Sydney, Australia
- Department of General Surgery, Calvary Health Care, Canberra, Australia
- School of Medicine, Australian National University, Canberra, Australia
| | - John F Thompson
- Melanoma Institute Australia, The University of Sydney, Sydney, Australia
- Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, Australia
- Discipline of Surgery, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
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13
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Henderson MA. Topical and intralesional therapies for in-transitmelanoma. Melanoma Manag 2019; 6:MMT23. [PMID: 31807274 PMCID: PMC6891934 DOI: 10.2217/mmt-2019-0008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Accepted: 05/08/2019] [Indexed: 01/03/2023] Open
Abstract
This report surveys the role of topical and intralesional agents in the management of in-transit melanoma. The extent and progression of in-transit disease is highly variable and many patients can have a protracted period of locoregional control. These agents are useful in the management of patients who have progressed beyond local surgical excision in whom more aggressive therapies, such as isolated limb infusion or use of talimogene laherparepvec, are not appropriate or have failed. In general, these agents are modestly effective and associated with frequent but only minor toxicity. As the mechanism of action of many of these agents includes initiation of a local immune response, combinations with immune checkpoint inhibitors are currently being explored.
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Affiliation(s)
- Michael A Henderson
- Division of Cancer Surgery, Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, Victoria 3000, Australia
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14
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Read T, Lonne M, Sparks DS, David M, Wagels M, Schaider H, Soyer HP, Smithers BM. A systematic review and meta‐analysis of locoregional treatments for in‐transit melanoma. J Surg Oncol 2019; 119:887-896. [DOI: 10.1002/jso.25400] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2018] [Revised: 01/13/2019] [Accepted: 01/19/2019] [Indexed: 12/18/2022]
Affiliation(s)
- Tavis Read
- Queensland Melanoma Project, Princess Alexandra HospitalBrisbane Queensland Australia
- The University of Queensland, Faculty of Medicine, Princess Alexandra HospitalBrisbane Queensland Australia
- Griffith University, School of MedicineGold Coast Queensland Australia
| | - Michael Lonne
- The University of Queensland, Faculty of Medicine, Princess Alexandra HospitalBrisbane Queensland Australia
| | - David S. Sparks
- The University of Queensland, Faculty of Medicine, Princess Alexandra HospitalBrisbane Queensland Australia
| | - Michael David
- The University of Queensland, School of Health and Rehabilitation SciencesBrisbane Queensland Australia
- The University of Newcastle, School of Medicine and Public HealthNewcastle New South Wales Australia
| | - Michael Wagels
- Queensland Melanoma Project, Princess Alexandra HospitalBrisbane Queensland Australia
- The University of Queensland, Faculty of Medicine, Princess Alexandra HospitalBrisbane Queensland Australia
| | - Helmut Schaider
- The University of Queensland, Dermatology Research CentreBrisbane Queensland Australia
| | - H. Peter Soyer
- The University of Queensland, Dermatology Research CentreBrisbane Queensland Australia
| | - B. Mark Smithers
- Queensland Melanoma Project, Princess Alexandra HospitalBrisbane Queensland Australia
- The University of Queensland, Faculty of Medicine, Princess Alexandra HospitalBrisbane Queensland Australia
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15
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Racz JM, Block MS, Baum CL, Jakub JW. Management of local or regional non‐nodal disease. J Surg Oncol 2018; 119:187-199. [DOI: 10.1002/jso.25330] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Accepted: 11/19/2018] [Indexed: 12/31/2022]
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16
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Responses to Topical Diphenylcyclopropenone as an Adjunct Treatment for In-Transit Melanoma: A Tertiary Referral Center Experience. Dermatol Surg 2018; 44:1501-1508. [DOI: 10.1097/dss.0000000000001603] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Nan Tie E, Henderson MA, Gyorki DE. Management of in-transit melanoma metastases: a review. ANZ J Surg 2018; 89:647-652. [PMID: 30414233 DOI: 10.1111/ans.14921] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2018] [Revised: 09/04/2018] [Accepted: 09/25/2018] [Indexed: 02/06/2023]
Abstract
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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Affiliation(s)
- Emilia Nan Tie
- Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Michael A Henderson
- Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.,Department of Surgery, St Vincent's Hospital, The University of Melbourne, Melbourne, Victoria, Australia
| | - David E Gyorki
- Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.,Department of Surgery, St Vincent's Hospital, The University of Melbourne, Melbourne, Victoria, Australia
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Tanita K, Fujimura T, Kambayashi Y, Tsukada A, Sato Y, Hashimoto A, Aiba S. Intensity-Modulated Radiotherapy Triggers Onset of Bullous Pemphigoid in a Patient with Advanced Melanoma Treated with Nivolumab. Case Rep Oncol 2018; 11:114-118. [PMID: 29606949 PMCID: PMC5869583 DOI: 10.1159/000487127] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Accepted: 01/25/2018] [Indexed: 01/02/2023] Open
Abstract
Since the efficacy of ipilimumab on nivolumab-resistant advanced melanoma is extremely low, additional supportive therapy for anti-PD-1 antibody therapy-resistant advanced melanoma is needed. Although several supportive therapies that enhance the antitumor immune response of anti-PD-1 antibodies have already been reported, unexpected immune-related adverse events were detected at the same time. In this report, we describe a patient with advanced melanoma treated with nivolumab followed by intensity-modulated radiotherapy, which might have triggered bullous pemphigoid (BP). Although several cases of BP developing in anti-PD-1 antibody-treated patients have already been reported, in this report, we shed light on the possible pathogenesis of BP developing in a patient treated with nivolumab through M2 macrophages.
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Affiliation(s)
- Kayo Tanita
- Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Taku Fujimura
- Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yumi Kambayashi
- Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Akira Tsukada
- Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yota Sato
- Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Akira Hashimoto
- Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Setsuya Aiba
- Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan
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Read T, Webber S, Thomas J, Wagels M, Schaider H, Soyer HP, Smithers BM. Protocol for the TIDAL Melanoma Study: topical imiquimod or diphenylcyclopropenone for the management of cutaneous in-transit melanoma metastases-a phase II, single centre, randomised, pilot study. BMJ Open 2017; 7:e016816. [PMID: 28988173 PMCID: PMC5640002 DOI: 10.1136/bmjopen-2017-016816] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
INTRODUCTION Patients with in-transit melanoma metastases present a therapeutic challenge. Complete surgical excision of localised disease is considered as the gold standard; however, surgery is not always acceptable and alternatives are required. Treatment results reported using imiquimod and diphenylcyclopropenone (DPCP) suggest that topical immunotherapies can be used to successfully treat select patients with melanoma metastases. A phase II, randomised, single centre, pilot study was designed to assess the clinical efficacy and safety of DPCP and imiquimod for the treatment of superficial, cutaneous in-transit melanoma metastases. METHODS AND ANALYSIS This is an open-label, non-superiority, pilot study with no treatment cross-over. Eligible patients are randomised in a 1:1 ratio to receive topical therapy for up to 12 months with a minimum follow-up period of 12 months. The target sample size is 30 patients, with 15 allocated to each treatment arm. The primary endpoint is the number of patients experiencing a complete response of treated lesions as determined clinically using Response Evaluation Criteria in Solid Tumours. This trial incorporates health-related quality of life measures and biological tissue collection for further experimental substudies. The study will also facilitate a health economic analysis. ETHICS AND DISSEMINATION Approval was obtained from the Human Research Ethics Committee at the participating centre, and recruitment has commenced. The results of this study will be submitted for formal publication within a peer-reviewed journal. TRIAL REGISTRATION NUMBER Prospectively registered on 16 October 2015 with the Australian New Zealand Clinical Trials Registry (ACTRN12615001088538). This study conforms to WHO Trial Registration Data Set.
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Affiliation(s)
- Tavis Read
- Queensland Melanoma Project, Princess Alexandra Hospital, Queensland Health, Brisbane, Australia
- Department of Surgery, The University of Queensland, School of Medicine, Princess Alexandra Hospital, Brisbane, Australia
- Griffith University, School of Medicine, Gold Coast, Australia
| | - Scott Webber
- Dermatology Research Centre, The University of Queensland Diamantina Institute, Brisbane, Australia
- Department of Dermatology, The University of Queensland, School of Medicine, Princess Alexandra Hospital, Brisbane, Australia
| | - Janine Thomas
- Queensland Melanoma Project, Princess Alexandra Hospital, Queensland Health, Brisbane, Australia
| | - Michael Wagels
- Queensland Melanoma Project, Princess Alexandra Hospital, Queensland Health, Brisbane, Australia
- Department of Surgery, The University of Queensland, School of Medicine, Princess Alexandra Hospital, Brisbane, Australia
| | - Helmut Schaider
- Dermatology Research Centre, The University of Queensland Diamantina Institute, Brisbane, Australia
- Department of Dermatology, The University of Queensland, School of Medicine, Princess Alexandra Hospital, Brisbane, Australia
| | - H Peter Soyer
- Dermatology Research Centre, The University of Queensland Diamantina Institute, Brisbane, Australia
- Department of Dermatology, The University of Queensland, School of Medicine, Princess Alexandra Hospital, Brisbane, Australia
| | - B Mark Smithers
- Queensland Melanoma Project, Princess Alexandra Hospital, Queensland Health, Brisbane, Australia
- Department of Surgery, The University of Queensland, School of Medicine, Princess Alexandra Hospital, Brisbane, Australia
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