Chemotherapy in the Management of Advanced Cutaneous Malignant Melanoma

Overview

Journal Clin Dermatol

Publisher Elsevier

Specialty Dermatology

Date 2013 Apr 24

PMID 23608448

Citations 43

Authors

Jason J Luke

Gary K Schwartz

Affiliations

Soon will be listed here.

Abstract

The recent past has witnessed unprecedented clinical progress in the treatment of advanced malignant melanoma through targeting of mutant BRAF in approximately 50% of patients and immune check point blockade in all patients. As has been well documented, responses to targeted therapy are of limited duration, and rates of clinical benefit to immunotherapy are modest. Given these factors, palliation of patients with chemotherapy remains an essential aspect of melanoma oncology. Many chemotherapeutics (and combinations with other agents, such as immunotherapy) have been evaluated in melanoma, although no chemotherapy regimen has been documented to provide an overall survival benefit in a prospective, randomized, well-controlled phase III study. We provide an overview of the development of the most common chemotherapy regimens for melanoma, discuss the clinical trial evidence supporting and contrasting them, and highlight appropriate clinical situations in which they might be used. We also discuss the future of chemotherapy for melanoma, noting the potential for combinations of chemotherapy with either targeted or immunotherapeutic agents.

Citing Articles

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Development of Thermoresponsive Composite Hydrogel Loaded with Indocyanine Green and Camptothecin for Photochemotherapy of Skin Cancer After Surgery.

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Liposomal Formulation of an Organogold Complex Enhancing Its Activity as Antimelanoma Agent-In Vitro and In Vivo Studies.

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Marizomib Promotes Senescence or Long-Term Apoptosis in Melanoma Cancer Cells.

Piskorz W, Kretowski R, Cechowska-Pasko M Molecules. 2024; 29(23).

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Liver Metastases are Associated with a Short Post-Progression Survival in a Real-World Group of Patients with Melanoma Treated with Checkpoint Inhibitors.

Mengoni M, Tuting T, Gaffal E, Braun A Oncol Ther. 2024; 13(1):131-143.

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References

Shah G, Socci N, Gold J, Wolchok J, Carvajal R, Panageas K . Phase II trial of neoadjuvant temozolomide in resectable melanoma patients. Ann Oncol. 2010; 21(8):1718-1722. DOI: 10.1093/annonc/mdp593. View

Bajetta E, Del Vecchio M, Bernard-Marty C, Vitali M, Buzzoni R, Rixe O . Metastatic melanoma: chemotherapy. Semin Oncol. 2002; 29(5):427-45. DOI: 10.1053/sonc.2002.35238. View

Eigentler T, Weide B, De Braud F, Spitaleri G, Romanini A, Pflugfelder A . A dose-escalation and signal-generating study of the immunocytokine L19-IL2 in combination with dacarbazine for the therapy of patients with metastatic melanoma. Clin Cancer Res. 2011; 17(24):7732-42. DOI: 10.1158/1078-0432.CCR-11-1203. View

Ranson M, Middleton M, Bridgewater J, Lee S, Dawson M, Jowle D . Lomeguatrib, a potent inhibitor of O6-alkylguanine-DNA-alkyltransferase: phase I safety, pharmacodynamic, and pharmacokinetic trial and evaluation in combination with temozolomide in patients with advanced solid tumors. Clin Cancer Res. 2006; 12(5):1577-84. DOI: 10.1158/1078-0432.CCR-05-2198. View

Li C, Chi S, Xie J . Hedgehog signaling in skin cancers. Cell Signal. 2011; 23(8):1235-43. PMC: 3122959. DOI: 10.1016/j.cellsig.2011.03.002. View

Agarwala S, Keilholz U, Gilles E, Bedikian A, Wu J, Kay R . LDH correlation with survival in advanced melanoma from two large, randomised trials (Oblimersen GM301 and EORTC 18951). Eur J Cancer. 2009; 45(10):1807-14. DOI: 10.1016/j.ejca.2009.04.016. View

Margolin K, Liu P, Flaherty L, Sosman J, Walker M, Smith 3rd J . Phase II study of carmustine, dacarbazine, cisplatin, and tamoxifen in advanced melanoma: a Southwest Oncology Group study. J Clin Oncol. 1998; 16(2):664-9. DOI: 10.1200/JCO.1998.16.2.664. View

Antony P, Piccirillo C, Akpinarli A, Finkelstein S, Speiss P, Surman D . CD8+ T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally occurring T regulatory cells. J Immunol. 2005; 174(5):2591-601. PMC: 1403291. DOI: 10.4049/jimmunol.174.5.2591. View

Palma J, Wang Y, Rodriguez L, Montgomery D, Ellis P, Bukofzer G . ABT-888 confers broad in vivo activity in combination with temozolomide in diverse tumors. Clin Cancer Res. 2009; 15(23):7277-90. DOI: 10.1158/1078-0432.CCR-09-1245. View

10.

Bajetta E, Del Vecchio M, Nova P, Fusi A, Daponte A, Sertoli M . Multicenter phase III randomized trial of polychemotherapy (CVD regimen) versus the same chemotherapy (CT) plus subcutaneous interleukin-2 and interferon-alpha2b in metastatic melanoma. Ann Oncol. 2006; 17(4):571-7. DOI: 10.1093/annonc/mdl007. View

11.

Creagan E, Suman V, Dalton R, Pitot H, Long H, Veeder M . Phase III clinical trial of the combination of cisplatin, dacarbazine, and carmustine with or without tamoxifen in patients with advanced malignant melanoma. J Clin Oncol. 1999; 17(6):1884-90. DOI: 10.1200/JCO.1999.17.6.1884. View

12.

Rietschel P, Wolchok J, Krown S, Gerst S, Jungbluth A, Busam K . Phase II study of extended-dose temozolomide in patients with melanoma. J Clin Oncol. 2008; 26(14):2299-304. DOI: 10.1200/JCO.2007.14.5292. View

13.

Gattinoni L, Finkelstein S, Klebanoff C, Antony P, Palmer D, Spiess P . Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells. J Exp Med. 2005; 202(7):907-12. PMC: 1397916. DOI: 10.1084/jem.20050732. View

14.

Ridolfi R, Chiarion-Sileni V, Guida M, Romanini A, Labianca R, Freschi A . Cisplatin, dacarbazine with or without subcutaneous interleukin-2, and interferon alpha-2b in advanced melanoma outpatients: results from an Italian multicenter phase III randomized clinical trial. J Clin Oncol. 2002; 20(6):1600-7. DOI: 10.1200/JCO.2002.20.6.1600. View

15.

Hersh E, ODay S, Ribas A, Samlowski W, Gordon M, Shechter D . A phase 2 clinical trial of nab-paclitaxel in previously treated and chemotherapy-naive patients with metastatic melanoma. Cancer. 2009; 116(1):155-63. DOI: 10.1002/cncr.24720. View

16.

Homsi J, Bedikian A, Kim K, Papadopoulos N, Hwu W, Mahoney S . Phase 2 open-label study of weekly docosahexaenoic acid-paclitaxel in cutaneous and mucosal metastatic melanoma patients. Melanoma Res. 2009; 19(4):238-42. DOI: 10.1097/CMR.0b013e32832a1e2f. View

17.

Legha S, Ring S, Eton O, Bedikian A, Buzaid A, Plager C . Development of a biochemotherapy regimen with concurrent administration of cisplatin, vinblastine, dacarbazine, interferon alfa, and interleukin-2 for patients with metastatic melanoma. J Clin Oncol. 1998; 16(5):1752-9. DOI: 10.1200/JCO.1998.16.5.1752. View

18.

Nelimark R, Peterson B, VOSIKA G, CONROY J . Vindesine for metastatic malignant melanoma. A phase II trial. Am J Clin Oncol. 1983; 6(5):561-4. View

19.

Bedikian A, Papadopoulos N, Kim K, Vardeleon A, Smith T, Lu B . A pilot study with vincristine sulfate liposome infusion in patients with metastatic melanoma. Melanoma Res. 2008; 18(6):400-4. DOI: 10.1097/CMR.0b013e328311aaa1. View

20.

Einzig A, Hochster H, Wiernik P, Trump D, Dutcher J, Garowski E . A phase II study of taxol in patients with malignant melanoma. Invest New Drugs. 1991; 9(1):59-64. DOI: 10.1007/BF00194546. View