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British Journal of Cancer logoLink to British Journal of Cancer
. 2000 Jun;82(11):1759–1763. doi: 10.1054/bjoc.2000.1141

Phase II study of second-line therapy with DTIC, BCNU, cisplatin and tamoxifen (Dartmouth regimen) chemotherapy in patients with malignant melanoma previously treated with dacarbazine

D J Propper 1, J P Braybrooke 1, N C Levitt 1, K O'Byrne 1, K Christodoulos 1, C Han 1, D C Talbot 1, T S Ganesan 1, A L Harris 1
PMCID: PMC2363219  PMID: 10839287

Abstract

This study assessed response rates to combination dacarbazine (DTIC), BCNU (carmustine), cisplatin and tamoxifen (DBPT) chemotherapy in patients with progressive metastatic melanoma previously treated with DTIC, as an evaluation of DBPT as a second-line regimen, and as an indirect comparison of DBPT with DTIC. Thirty-five consecutive patients received DBPT. The patients were divided into two groups. Group 1 comprised 17 patients with progressive disease (PD) on DTIC + tamoxifen therapy who were switched directly to DBPT. Group 2 comprised 18 patients not immediately switched to DBPT and included patients who had either a partial response (PR; one patient) or developed stable disease (SD; four patients) with DTIC, or received adjuvant DTIC (nine patients). All except four patients had received tamoxifen at the time of initial DTIC treatment. Median times since stopping DTIC were 22 days (range 20–41) and 285 days (range 50–1240) in Groups 1 and 2 respectively. In Group 1, one patient developed SD for 5 months and the remainder had PD. In Group 2, there were two PRs, four patients with SD (4, 5, 6, and 6 months), and 11 with PD. These results indicate that the DBPT regimen is not of value in melanoma primarily refractory to DTIC. There were responses in patients not directly switched from DTIC to DBPT, suggesting combination therapy may be of value in a small subgroup of melanoma patients. © 2000 Cancer Research Campaign

Keywords: melanoma, DTIC, Dartmouth regimen

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Selected References

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  1. Bajetta E., Buzzoni R., Vicario G. Combined carboplatin and cytosine arabinoside in metastatic melanoma refractory to dacarbazine. Tumori. 1995 Jul-Aug;81(4):238–240. doi: 10.1177/030089169508100404. [DOI] [PubMed] [Google Scholar]
  2. Braybrooke J. P., Houlbrook S., Crawley J. E., Propper D. J., O'Byrne K. J., Stratford I. J., Harris A. L., Shuker D. E., Talbot D. C. Evaluation of the alkaline comet assay and urinary 3-methyladenine excretion for monitoring DNA damage in melanoma patients treated with dacarbazine and tamoxifen. Cancer Chemother Pharmacol. 2000;45(2):111–119. doi: 10.1007/s002800050018. [DOI] [PubMed] [Google Scholar]
  3. Cree I. A., Kurbacher C. M. Individualizing chemotherapy for solid tumors--is there any alternative? Anticancer Drugs. 1997 Jul;8(6):541–548. doi: 10.1097/00001813-199707000-00001. [DOI] [PubMed] [Google Scholar]
  4. Del Prete S. A., Maurer L. H., O'Donnell J., Forcier R. J., LeMarbre P. Combination chemotherapy with cisplatin, carmustine, dacarbazine, and tamoxifen in metastatic melanoma. Cancer Treat Rep. 1984 Nov;68(11):1403–1405. [PubMed] [Google Scholar]
  5. Dorval T., Négrier S., Chevreau C., Avril M. F., Baume D., Cupissol D., Oskam R., de Peuter R., Vinke J., Herrera A. Randomized trial of treatment with cisplatin and interleukin-2 either alone or in combination with interferon-alpha-2a in patients with metastatic melanoma: a Federation Nationale des Centres de Lutte Contre le Cancer Multicenter, parallel study. Cancer. 1999 Mar 1;85(5):1060–1066. doi: 10.1002/(sici)1097-0142(19990301)85:5<1060::aid-cncr8>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  6. Everall J. D., Dowd P. M. Use of combination chemotherapy with CCNU, bleomycin, and vincristine in the treatment of metastatic melanoma in patients resistant to DTIC therapy. Cancer Treat Rep. 1979 Jan;63(1):151–155. [PubMed] [Google Scholar]
  7. GEHAN E. A. The determinatio of the number of patients required in a preliminary and a follow-up trial of a new chemotherapeutic agent. J Chronic Dis. 1961 Apr;13:346–353. doi: 10.1016/0021-9681(61)90060-1. [DOI] [PubMed] [Google Scholar]
  8. Hill G. J., 2nd, Krementz E. T., Hill H. Z. Dimethyl triazeno imidazole carboxamide and combination therapy for melanoma. IV. Late results after complete response to chemotherapy (Central Oncology Group protocols 7130, 7131, and 7131A). Cancer. 1984 Mar 15;53(6):1299–1305. doi: 10.1002/1097-0142(19840315)53:6<1299::aid-cncr2820530613>3.0.co;2-4. [DOI] [PubMed] [Google Scholar]
  9. Johnson D. H., Presant C., Einhorn L., Bartolucci A. A., Greco F. A. Cisplatin, vinblastine, and bleomycin in the treatment of metastatic melanoma: a phase II study of the Southeastern Cancer Study Group. Cancer Treat Rep. 1985 Jul-Aug;69(7-8):821–824. [PubMed] [Google Scholar]
  10. Johnston S. R., Constenla D. O., Moore J., Atkinson H., A'Hern R. P., Dadian G., Riches P. G., Gore M. E. Randomized phase II trial of BCDT [carmustine (BCNU), cisplatin, dacarbazine (DTIC) and tamoxifen] with or without interferon alpha (IFN-alpha) and interleukin (IL-2) in patients with metastatic melanoma. Br J Cancer. 1998 Apr;77(8):1280–1286. doi: 10.1038/bjc.1998.214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lee S. M., Thatcher N., Margison G. P. O6-alkylguanine-DNA alkyltransferase depletion and regeneration in human peripheral lymphocytes following dacarbazine and fotemustine. Cancer Res. 1991 Jan 15;51(2):619–623. [PubMed] [Google Scholar]
  12. Margolin K. A., Liu P. Y., Flaherty L. E., Sosman J. A., Walker M. J., Smith J. W., 3rd, Fletcher W. S., Weiss G. R., Unger J. M., Sondak V. K. Phase II study of carmustine, dacarbazine, cisplatin, and tamoxifen in advanced melanoma: a Southwest Oncology Group study. J Clin Oncol. 1998 Feb;16(2):664–669. doi: 10.1200/JCO.1998.16.2.664. [DOI] [PubMed] [Google Scholar]
  13. Mc Clay E. F., Mc Clay M. E., Albright K. D., Jones J. A., Christen R. D., Alcaraz J., Howell S. B. Tamoxifen modulation of cisplatin resistance in patients with metastatic melanoma. A biologically important observation. Cancer. 1993 Sep 15;72(6):1914–1918. doi: 10.1002/1097-0142(19930915)72:6<1914::aid-cncr2820720620>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
  14. Mc Clay E. F., Mc Clay M. E. Systemic chemotherapy for the treatment of metastatic melanoma. Semin Oncol. 1996 Dec;23(6):744–753. [PubMed] [Google Scholar]
  15. McClay E. F., Albright K. D., Jones J. A., Christen R. D., Howell S. B. Tamoxifen modulation of cisplatin sensitivity in human malignant melanoma cells. Cancer Res. 1993 Apr 1;53(7):1571–1576. [PubMed] [Google Scholar]
  16. McClay E. F., McClay M. E. Tamoxifen: is it useful in the treatment of patients with metastatic melanoma? J Clin Oncol. 1994 Mar;12(3):617–626. doi: 10.1200/JCO.1994.12.3.617. [DOI] [PubMed] [Google Scholar]
  17. Mulder N. H., Sleijfer D. T., de Vries E. G., Schraffordt Koops H., Willemse P. H. Phase II study of carboplatin and cytosine arabinoside in patients with disseminated malignant melanoma. J Cancer Res Clin Oncol. 1990;116(3):301–302. doi: 10.1007/BF01612907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Philip P. A., Carmichael J., Tonkin K., Ganesan T. A., Harris A. L. A phase II study of high-dose hydroxyurea and dacarbazine (DTIC) in the treatment of metastatic malignant melanoma. Eur J Cancer. 1994;30A(7):1027–1029. doi: 10.1016/0959-8049(94)90137-6. [DOI] [PubMed] [Google Scholar]
  19. Porcile G., Musso M., Boccardo F., Rosso R., Santi L. Combination chemotherapy with vinblastine, bleomycin and methotrexate in DTIC-resistant metastatic melanoma. Tumori. 1979 Apr 30;65(2):237–240. doi: 10.1177/030089167906500213. [DOI] [PubMed] [Google Scholar]
  20. Propper D. J., Macaulay V., O'Byrne K. J., Braybrooke J. P., Wilner S. M., Ganesan T. S., Talbot D. C., Harris A. L. A phase II study of bryostatin 1 in metastatic malignant melanoma. Br J Cancer. 1998 Nov;78(10):1337–1341. doi: 10.1038/bjc.1998.680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Quagliana J. M., Stephens R. L., Baker L. H., Costanzi J. J. Vindesine in patients with metastatic malignant melanoma: a Southwest Oncology Group study. J Clin Oncol. 1984 Apr;2(4):316–319. doi: 10.1200/JCO.1984.2.4.316. [DOI] [PubMed] [Google Scholar]
  22. Reintgen D., Saba H. Chemotherapy for stage 4 melanoma: a three-year experience with cisplatin, DTIC, BCNU, and tamoxifen. Semin Surg Oncol. 1993 May-Jun;9(3):251–255. [PubMed] [Google Scholar]
  23. Rusciani L., Petraglia S., Alotto M., Calvieri S., Vezzoni G. Postsurgical adjuvant therapy for melanoma. Evaluation of a 3-year randomized trial with recombinant interferon-alpha after 3 and 5 years of follow-up. Cancer. 1997 Jun 15;79(12):2354–2360. doi: 10.1002/(sici)1097-0142(19970615)79:12<2354::aid-cncr9>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
  24. Saunders M. P., Salisbury A. J., O'Byrne K. J., Souliotis V. L., Varcoe S. M., Talbot D. C., Kyrtopoulos S. A., Harris A. L. A phase II study evaluating the effect of tamoxifen on DNA repair in melanoma patients treated with dacarbazine. Anticancer Res. 1997 Nov-Dec;17(6D):4677–4680. [PubMed] [Google Scholar]

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