Abstract
Purpose
To scrutinize published data from small mono-centric studies and case reports which implicated high response rates and promising survival times for a combination therapy consisting of epifocal dinitrochlorobenzene (DNCB) and dacarbazine (DTIC) for metastasized melanoma. This therapy merges the effects of an allergic contact dermatitis elicited at the site of a cutaneous metastasis, and systemic chemotherapy.
Methods
We performed a retrospective survey with nine German centers and evaluated 72 patients treated from 1993 to 2005.
Results
The objective response rate in stage III melanoma (n = 39) was 62%. In contrast, only 9% objective responses were observed in 33 stage IV patients. Interestingly, more than half of patients with objective remissions remained progression-free for more than 1 year irrespective of the stage of disease.
Conclusions
Epifocal DNCB combined with DTIC is effective in patients with regionally metastasized melanoma not amenable to surgery or isolated limb perfusion, whereas in stage IV disease in spite of few durable remissions the addition of DNCB does not improve the therapeutic efficacy of DTIC.
Similar content being viewed by others
References
Avril MF, Aamdal S, Grob JJ, Hauschild A, Mohr P, Bonerandi JJ, Weichenthal M, Neuber K, Bieber T, Gilde K, Guillem Porta V, Fra J, Bonneterre J, Saiag P, Kamanabrou D, Pehamberger H, Sufliarsky J, Gonzales Larriba JL, Scherrer A, Menu Y (2004) Fotemustine compared with dacarbazine in patients with disseminated malignant melanoma: a phase III study. J Clin Oncol 22:1118–1125
Bach AG, Marsch WC, Richter C, Lübbe D, Helmbold P (2005) Langfristig lokal rezidiviertes malignes Melanom. Hautarzt 56:949–954
Balch CM, Buzaid AC, Soong S-J, Atkins AB, Cascinelli N, Coit DC, Fleming ID, Gershenwald JE, Houghton A, Kirkwood JM, McMasters KM, Mihm FM, Morton DL, Reintgen DS, Ross MI, Sober A, Thompson JA, Thompson JF (2001) Final version of the American Joint Comittee on Cancer staging system for cutaneous melanoma. J Clin Oncol 19:3635–3648
Becker JC, Kämpgen E, Bröcker EB (2000) Classical chemotherapy for metastatic melanoma. Clin Exp Dermatol 25:503–508
Budzanowska E, Pawlicki M (1988) An attempt at topical DNCB immunomodulation in advanced malignant melanoma. Tumori 74:519–522
Burg G, Braun-Falco O (1977) 1-Chlor-2, 4-dinitrobenzol(DNCB)-Salbe zur Sensibilisierung, Testung und Behandlung von Patienten mit malignem Melanom. Dtsch Med Wochenschr 102:210–211
Chapman PB, Einhorn LH, Meyers ML, Saxman S, Destro AN, Panageas KS, Begg CB, Agarwala SS, Schuchter LM, Ernsthoff MS, Houghton AN, Kirkwood JM (1999) Phase III multicenter randomized trial of the Dartmouth regimen versus dacarbazine in patients with metastatic melanoma. J Clin Oncol 17:2745–2751
Drepper H, Biess B, Hofherr B, Hundeiker M, Lippold A, Otto F, Padberg G, Peters A, Wiebelt H (1993) The prognosis of patients with stage III melanoma. Prospective long-term study of 286 patients of the Fachklinik Hornheide. Cancer 71:1239–1246
Eton O, Legha SS, Moon TE, Buzaid AC, Papadopoulos N, Plager C, Burgess A, Bedikian A, Ring S, Dong Q, Glassman A, Balch CM, Benjamin RS (1998) Prognostic factors for survival of patients treated systemically for disseminated melanoma. J Clin Oncol 16:1103–1111
Flaherty LE, Liu PY, Unger J, Sondak VK (1997) Comparison of patient characteristics and outcome between a single-institution phase II trial and a cooperative-group phase II trial with identical eligibility in metastatic melanoma. Am J Clin Oncol 20:600–604
Göring HD, Ziemer A, Kröning Y, Trebing D, Kämpgen E, Bröcker EB (1998) Effective combined immunotherapy with dinitrochlorobenzene and fotemustine in skin and brain metastases of melanoma. Melanoma Res 8:379
Haffner AC, Garbe C, Burg G, Buttner P, Orfanos CE, Rassner G (1992) The prognosis of primary and metastasising melanoma. An evaluation of the TNM classification in 2,495 patients. Br J Cancer 66:856–861
Illig L, Paul E (1976) Unspezifische epifokale Immuntherapie des malignen Melanoms der Haut mit DNCB nach Malek-Mansour. Hautarzt 27:579–587
Illig L, Paul E, Bödeker RH (1984) Epifocal dinitrochlorobenzene therapy in malignant melanoma (experience during the last eight years). Anticancer Res 4:293–298
Inbar M, Merimsky O, Stein JA (1996) DNCB for local control of malignant melanoma: don’t forget a winning horse. Melanoma Res 6:457–459
Junghans V, Menzel S, Rünger TM (1998) Erfolgreiche Therapie mit Dacarbazin und lokaler Applikation des Kontaktallergens Dinitrochlorbenzol bei therapieresistentem, in-transit- und fernmetastasiertem Melanom. Aktuelle Derm 24:332–335
Khayat D, Bernard-Marty C, Meric J-B, Rixe O (2002) Biochemotherapy for advanced melanoma: maybe it is real. J Clin Oncol 20:2411–2414
Kroon BBR, Noorda EM, Vrouenraets BC, Nieweg OE (2002) Isolated limb perfusion for melanoma. J Surg Oncol 79:252–255
Loth H, Ehring F (1978) Die Behandlung des malignen Melanoms mit Dinitrochlorbenzol-Salbe. Hautarzt 29:141–146
Malek-Mansour S (1973) Remission of melanoma with DNCB treatment. Lancet 2:503–504
Meier F, Will S, Ellwanger U, Schlagenhauff B, Schittek B, Rassner G, Garbe C (2002) Metastatic pathways and time courses in the orderly progression of cutaneous melanoma. Br J Dermatol 147:62–70
Middleton MR, Grob JJ, Aaronson N, Fierlbeck G, Tilgen W, Seiter S, Gore M, Aamdal S, Cebon J, Coates A, Dreno B, Henz M, Schadendorf D, Kapp A, Weiss J, Fraass U, Statkevich P, Muller M, Thatcher N (2000) Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol 18:158–166
von Nida J, Quirk C (2003) Successful treatment of in-transit metastases using topical 2–4 dinitrochlorobenzene. Australas J Dermatol 44:277–280
Rümke P (1992) Melanoma treatment: a key role for immunotherapy with chemotherapy. Medicographia 14:47–49
Schadendorf D, Ugurel S, Schuler-Thurner B, Nestle FO, Enk A, Bröcker EB, Grabbe S, Rittgen W, Edler L, Sucker A, Zimpfer-Rechner C, Berger T, Kamarashev J, Burg G, Jonuleit H, Tuttenberg A, Becker JC, Keikavoussi P, Kämpgen E, Schuler G (2006) Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: a randomized phase III trial of the DC study group of the DeCOG. Ann Oncol 17:563–570
Schuler-Thurner B, Schuler G (2005) Vaccination therapy of melanoma. JDDG 3:630–645
Strobbe LJA, Hart AAM, Rümke Ph, Israels SP, Nieweg OE, Kroon BBR (1997) Topical dinitrochlorobenzene combined with systemic dacarbazine in the treatment of recurrent melanoma. Melanoma Res 7:507–512
Trcka J, Kämpgen E, Becker JC, Schwaaf A, Bröcker EB (1998) Immunochemotherapie des malignen Melanoms: Epifokale Applikation von Dinitrochlorobenzol (DNCB) kombiniert mit systemischer Chemotherapie mit Dacarbazin (DTIC). Hautarzt 49:17–22
Trefzer U, Sterry W (2005) Topical immunotherapy with diphenylcyclopropenone in combination with DTIC and radiation for cutaneous metastases of melanoma. Dermatology 211:370–371
Truchetet F, Heid E, Friedel J, Chartier C, Grosshans E (1989) D.N.C.B. for malignant melanoma: significance in the treatment strategy. Anticancer Res 9:1531–1536
Wack C, Becker JC, Bröcker EB, Lutz WK, Fischer WH (2001) Chemoimmunotherapy for melanoma with dacarbazine and 2,4-dinitrochlorobenzene: results from a murine tumour model. Melanoma Res 11:247–253
Wack C, Kirst A, Becker JC, Lutz WK, Bröcker EB, Fischer WH (2002) Chemoimmunotherapy for melanoma with dacarbazine and 2,4-dinitrochlorobenzene elicits a specific T cell-dependent immune response. Cancer Immunol Immunother 51:431–439
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Terheyden, P., Kortüm, AK., Schulze, HJ. et al. Chemoimmunotherapy for cutaneous melanoma with dacarbazine and epifocal contact sensitizers: results of a nationwide survey of the German Dermatologic Co-operative Oncology Group. J Cancer Res Clin Oncol 133, 437–444 (2007). https://doi.org/10.1007/s00432-006-0182-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-006-0182-9