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. 1998 Oct;78(8):1076–1080. doi: 10.1038/bjc.1998.630

Risk and outcome in metastatic malignant melanoma patients receiving DTIC, cisplatin, BCNU and tamoxifen followed by immunotherapy with interleukin 2 and interferon alpha2a.

R Hoffmann 1, I Müller 1, K Neuber 1, S Lassmann 1, J Buer 1, M Probst 1, K Oevermann 1, A Franzke 1, H Kirchner 1, A Ganser 1, J Atzpodien 1
PMCID: PMC2063152  PMID: 9792153

Abstract

Combined chemo-/immunotherapy has shown high objective response rates and a significant though small proportion of long-term complete responders in metastatic malignant melanoma. The purpose of this study was to determine response rates, freedom from treatment failure (FFTF) and overall survival in patients with advanced metastatic malignant melanoma treated with combined chemo-/immunotherapy, and to determine the value of a prognostic model for prediction of treatment outcome, FFTF and survival. Sixty-nine patients with metastatic malignant melanoma received combined chemo-/immunotherapy consisting of up to four cycles of DTIC (220 mg m(-2) i.v. days 1-3), cisplatin (35 mg m(-2) i.v. days 1-3), BCNU (150 mg m(-2) i.v. day 1, cycles 1 and 3 only) and tamoxifen (20 mg orally, daily). Two cycles of chemotherapy were followed by 6 weeks of outpatient immunotherapy with combined interleukin 2 (20 x 10(6) IU m(-2) days 3-5, weeks 1 and 4; 5 x 10(6) IU m(-2) days 1, 3, 5, weeks 2, 3, 5, 6) and interferon-alpha (6 x 10(6) IU m(-2) s.c. day 1, weeks 1 and 4; days 1, 3, 5, weeks 2, 3, 5, 6). All patients were evaluated on an intention-to-treat basis. Of 69 patients entered in the study, seven achieved complete remissions and 20 reached partial remissions with an objective response rate of 39% (95% confidence interval 28-52%). Median survival was 11 months, median FFTF was 5 months. Seven patients achieved ongoing long-term remissions, with maximum survival of 58 + months, and maximum FFTF of 58 + months. By Kaplan-Meier survival analysis and two-proportional Cox regression analysis, pretreatment performance status and serum lactic dehydrogenase were statistically significant and independent predictors of survival; risk groups could be defined as (a) the absence of both or (b) the presence of either one or both of these risk factors. Whereas survival and response were significantly influenced by patient risk, no influence could be demonstrated for FFTF. This combined outpatient chemo-/immunotherapy is feasible and results in objective response rates and survival similar to earlier trials. Pretreatment risk, as defined by serum lactate dehydrogenase (LDH) and performance status, has a significant impact on treatment outcome and patient survival.

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Selected References

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  1. Atkins M. B., O'Boyle K. R., Sosman J. A., Weiss G. R., Margolin K. A., Ernest M. L., Kappler K., Mier J. W., Sparano J. A., Fisher R. I. Multiinstitutional phase II trial of intensive combination chemoimmunotherapy for metastatic melanoma. J Clin Oncol. 1994 Aug;12(8):1553–1560. doi: 10.1200/JCO.1994.12.8.1553. [DOI] [PubMed] [Google Scholar]
  2. Atzpodien J., Lopez Hänninen E., Kirchner H., Franzke A., Körfer A., Volkenandt M., Duensing S., Schomburg A., Chaitchik S., Poliwoda H. Chemoimmunotherapy of advanced malignant melanoma: sequential administration of subcutaneous interleukin-2 and interferon-alpha after intravenous dacarbazine and carboplatin or intravenous dacarbazine, cisplatin, carmustine and tamoxifen. Eur J Cancer. 1995 Jun;31A(6):876–881. doi: 10.1016/0959-8049(94)00459-5. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Guida M., Latorre A., Mastria A., De Lena M. Subcutaneous recombinant interleukin-2 plus chemotherapy with cisplatin and dacarbazine in metastatic melanoma. Eur J Cancer. 1996 Apr;32A(4):730–733. doi: 10.1016/0959-8049(95)00662-1. [DOI] [PubMed] [Google Scholar]
  5. Keilholz U., Goey S. H., Punt C. J., Proebstle T. M., Salzmann R., Scheibenbogen C., Schadendorf D., Liénard D., Enk A., Dummer R. Interferon alfa-2a and interleukin-2 with or without cisplatin in metastatic melanoma: a randomized trial of the European Organization for Research and Treatment of Cancer Melanoma Cooperative Group. J Clin Oncol. 1997 Jul;15(7):2579–2588. doi: 10.1200/JCO.1997.15.7.2579. [DOI] [PubMed] [Google Scholar]
  6. Kirkwood J. M., Strawderman M. H., Ernstoff M. S., Smith T. J., Borden E. C., Blum R. H. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol. 1996 Jan;14(1):7–17. doi: 10.1200/JCO.1996.14.1.7. [DOI] [PubMed] [Google Scholar]
  7. Legha S. S. Durable complete responses in metastatic melanoma treated with interleukin-2 in combination with interferon alpha and chemotherapy. Semin Oncol. 1997 Feb;24(1 Suppl 4):S39–S43. [PubMed] [Google Scholar]
  8. Probst-Kepper M., Schrader A., Buer J., Grosse J., Volkenandt M., Illiger H. J., Metzner B., Kadar J., Duensing S., Hertenstein B. Detection of melanoma cells in peripheral blood stem cell harvests of patients with progressive metastatic malignant melanoma. Br J Haematol. 1997 Aug;98(2):488–490. doi: 10.1046/j.1365-2141.1997.1963015.x. [DOI] [PubMed] [Google Scholar]
  9. Richards J. M., Gilewski T. A., Ramming K., Mitchel B., Doane L. L., Vogelzang N. J. Effective chemotherapy for melanoma after treatment with interleukin-2. Cancer. 1992 Jan 15;69(2):427–429. doi: 10.1002/1097-0142(19920115)69:2<427::aid-cncr2820690225>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  10. Richards J. M., Mehta N., Ramming K., Skosey P. Sequential chemoimmunotherapy in the treatment of metastatic melanoma. J Clin Oncol. 1992 Aug;10(8):1338–1343. doi: 10.1200/JCO.1992.10.8.1338. [DOI] [PubMed] [Google Scholar]
  11. Rosenberg S. A., Yang J. C., Topalian S. L., Schwartzentruber D. J., Weber J. S., Parkinson D. R., Seipp C. A., Einhorn J. H., White D. E. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA. 1994 Mar 23;271(12):907–913. [PubMed] [Google Scholar]
  12. Thompson J. A., Gold P. J., Fefer A. Outpatient chemoimmunotherapy for the treatment of metastatic melanoma. Semin Oncol. 1997 Feb;24(1 Suppl 4):S44–S48. [PubMed] [Google Scholar]

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