The treatment of metastatic melanoma with chemotherapy and biologics

Current Opinion in Oncology

Volumn 9, Issue 2, 1997, Pages 205-213

  Atkins, Michael B ^a  

^a BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA INTERFERON; BIOLOGICAL RESPONSE MODIFIER; BLEOMYCIN; CANCER VACCINE; CARBOPLATIN; CARMUSTINE; CISPLATIN; CYTARABINE; CYTOTOXIC AGENT; DACARBAZINE; DOCETAXEL; FOTEMUSTINE; GANGLIOSIDE ANTIBODY; HYDROXYUREA; INTERLEUKIN 12; INTERLEUKIN 2; INTERLEUKIN 4; INTERLEUKIN 6; LOMUSTINE; METHYLXANTHINE DERIVATIVE; NITROSOUREA; OXANTHRAZOLE; PACLITAXEL; PIRITREXIM; PLATINUM DERIVATIVE; TAMOXIFEN; TEMOZOLOMIDE; UNINDEXED DRUG; VINBLASTINE; ZENIPLATIN;

ADVERSE DRUG REACTION; ANTINEOPLASTIC ACTIVITY; BLOOD TOXICITY; CANCER COMBINATION CHEMOTHERAPY; CANCER IMMUNOTHERAPY; CLINICAL TRIAL; GASTROINTESTINAL SYMPTOM; HUMAN; INTRAVENOUS DRUG ADMINISTRATION; MELANOMA; METASTASIS; ORAL DRUG ADMINISTRATION; PRIORITY JOURNAL; REVIEW;

EID: 0030925810     PISSN: 10408746     EISSN: None     Source Type: Journal    
DOI: 10.1097/00001622-199703000-00016     Document Type: Review

References (71)

1. Barth A, Wanek LA, Morton DL: Prognostic factors in 1,521 melanoma patients with distant metastases. J Am Coll Surg 1995, 181:193-201. This is a retrospective analysis of a large database of patients with metastatic melanoma followed at a single institution over a 22-year period. It describes the natural history of metastatic melanoma and identifies several disease characteristics that are associated with prolonged survival. These include disease-free interval, certain initial sites of metastases, and the stage of disease preceding development of distant metastases. The authors recommend that these prognostic variables should be considered in the design of future phase III clinical trials.
2. Flaherty L, Unger J, Liu PY, Albain K, Sondak V: Gender differences and independent predictors of survival in patients with metastatic malignant melanoma [abstract]. Proc Am Soc Clin Oncol 1996, 15:433. This is a retrospective analysis of a database of 649 consecutive eligible patients enrolled in 11 SWOG trials evaluating systemic treatments for metastatic melanoma. In a multivariate analysis performance status, number of organs involved, disease-free interval, and the absence or presence of liver involvement were shown to be independent predictors of survival. In contrast, to previous studies, gender was not shown to be an independent variable. As with Barth et ai [1••], they recommended that these factors be used to stratify patients in future phase III trials.
3. Khayat D, Avril M, Auclerc G, ef al.: Clinical value of the nitrosourea fotemustine in disseminated malignant melanoma: overview on 1022 patients including 144 patients with cerebral metastases. Proc Am Soc Clin Oncol 1993, 12:393.
4. Lee SM, Betticher DC, Thatcher N: Melanoma: chemotherapy. Br Med Bull 1995, 51:3609-630. An excellent review of the status of single-agent and combination cytotoxic chemotherapy for melanoma. It includes a discussion of potential mechanisms of resistance as well as high-dose chemotherapy trials with autologous bone marrow rescue and the use of chemotherapy in the adjuvant setting.
5. Stevens MFG, Hickman JA, Langdon SP, Chubb D, Vickers L, Stone R, Baig G, Goddard C, Gibson NW, Slack JA, Newton C, Lunt E, Fizames C, Lavelle F: Antitumor activity and pharmacokinetics in mice of 8-carbamoyl-3-methylimidazo [5,1-d] 1,2,3,5-tetrazin-4 (3H) one (CCRG) 81045: M&B 39831 : a novel drug with potential as an alternative to dacarbazine. Cancer Res 1987, 47:5846-5852.
6. Bleehen NM, Newlands SM, Thatcher LN, Selby P, Calver AH, Rustin GJ, Brampton M. Stevens MFG: Cancer research campaign phase II trial of temozolomide in metastatic melanoma. J Clin Oncol 1995, 13:910-913. This is the first phase II clinical trial of the novel DTIC analogue, temozolomide, in patients with metastatic melanoma. This agent has the potential advantages of being orally absorbed and having excellent central nervous system penetration. Encouraging antitumor activity was noted, including a response in one of four patients with central nervous system metastases, with only moderate toxicity. Based on this data and its unique mode of administration, temozolomide is currently being intensively investigated in several different clinical situations, using a variety of clinical trial designs.
7. Bedikian A, Legha S, Jenkins J, Eton O, Buzaid A, Plager C, Papadopoulos N, Benjamin R: Phase II trial of docetaxel in patients (pts) with advanced melanoma previously untreated with chemotherapy [abstract]. Proc Am Soc Clin Oncol 1995, 14:412. This abstract describes the first clinical trial of docetaxel in metastatic melanoma. Encouraging clinical activity is reported with only modest toxicity.
8. Olver I, Green M, Peters W, Zimet A, Toner G, Bishop J, Ketelbey W, Rastogi R, Birkhofer M: A phase III trial of zenplatin In metastatic melanoma. Am J Clin Oncol 1995, 18:56-58.
9. Feun LG, Robinson WA, Savaraj N, Gonzalez R, Liebmann A, Offenhauser K, Clendeninn NJ: Phase II trial of piritrexim and DTIC using an alter-nating dose schedule in metastatic melanoma. Am J Clin Oncol (CCT) 1995, 18:488-490.
10. Sosman JA, Flaherty LE, Liu PY, Fletcher W, Thompson JA, Hantel A, Sondak V: A phase II trial of piroxantrone in disseminated malignant melanoma: a Southwest Oncology Group study. Invest New Drugs 1995, 13:83-87.
11. Bajetta E, Buzzoni R, Vicario G: Combined carboplatin and cytosine arabinoside in metastatic melanoma refractory to dacarbazine. Tumori 1995, 81:238-240. This study describes encouraging antitumor activity for this novel second-line treatment regimen. All responses were apparently partial, however, limiting its value.
12. Costanzi JJ, Al-Sarraf M, Groppe C, Bottomley R, Fabian C, Neidhart J, et al.: Combination chemotherapy plus BCG in the treatment of disseminated malignant melanoma: a Southwest Oncology Group study. Med Pediatr Oncol 1982, 10:251-258.
13. Luikart SD, Kennealey GT, Kirkwood JM: Randomized phase III trial of vinblastine, bleomycin and cis-dichlorodiammine-platinum versus dacarbazine in malignant melanoma. J Clin Oncol 1984, 2:164-168.
14. Buzaid AC, Legha S, Winn R, Belt R, Pollock T, Wiseman C, Ensign LG: Cisplatin (C), vinblastine (V), and dacarbazine (D) (CVD) versus dacarbazine alone in metastatic melanoma: preliminary results of a phase III Cancer Community Oncology Program (CCOP) trial [abstract]. Proc Am Soc Clin Oncol 1993, 12:389.
15. Rusthoven JJ, Quirt IC. Iscoe NA, McCulloch PB, James WK, Lohmann RC, Jensen J, Burdette-Radoux S, Bodurtha AJ, Silver HK, Verma S, Armitage GR, Zee B, Bennett K: Randomized, double-blind placebo-controlled trial comparing the response rates of carmustine, dacarbazine, and cisplatin with and without tamoxifen in patients with metastatic melanoma: National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 1996, 14:2083-2090. This study is a large multi-institutional, randomized phase III Cooperative Group trial that examines the value of adding high-dose tamoxifen to DTIC. cisplatin, and carmustine chemotherapy. Response rates were roughly equivalent for the two treatment groups and survival appeared unaffected by the addition of tamoxifen.
16. McClay EF, Mastrangelo MJ, Berd D, Bellet RE; Effective combination chemo/hormonal therapy for malignant melanoma: experience with three clinical trials, Int J Cancer 1992, 50:553-556.
17. Cocconi G, Bella M, Calabresi F, Tonato M, Canaletti R, Boni C, Buzzi F, Ceci G, Corgna E, Costa P, Lottich R, Papadia F, Sofra MC, Bacchi M: Treatment of metastatic malignant melanoma with dacarbazine plus tamoxifen. N Engl J Med 1992, 327:516-523.
18. Legha S, Ring S, Bedikian A, Eton O, Plager C, Papadopoulos N, Ensign LG, Benjamin RS: Lack of benefit from tamoxifen (T) added to a regimen of cisplatin (C), vinblastine (V), DTIC (D) and alpha Interferon (IFN) in patients (PT) with metastatic melanoma. Proc Am Soc Clin Oncol 1993, 12:388.
19. Ferri W, Agarwala SS, Kirkwood JM, Gooding W, Vlock D, Miketic L, Donnell S: Carboplatin and dacarbazine (D) ± tamoxifen (T) for metastatic melanoma. Proc Am Soc Clin Oncol 1994, 13:394.
20. Falkson CI, Ibrahim J, Kirkwood J, Blum R: A randomized phase III trial of dacarbazine (DTIC) versus DTIC + Interferon alfa-2b (IFN) versus DTIC + tamoxifen (TMX) versus DTIC + IFN + TMX in metastatic malignant melanoma: an ECOG tTrial [abstract] Proc Am Soc Clin Oncol 1996, 15:435. This is a large four-arm Cooperative Group trial performed within ECOG. A two by two trial design was used which allowed for the examination of both the value of adding tamoxifen to either DTIC alone or DTIC plus Interferon alfa and the value of adding Interferon alfa to either DTIC alone or DTIC plus tamoxifen. The DTIC plus tamoxifen and DTIC plus Interferon schedules were based on previously reported "positive" smaller scale randomized phase III trials. This trial conclusively showed that neither tamoxifen or interferon alfa add significantly to either the response rate or median survival in patients with metastatic melanoma.
21. Nathan FE, Sato T, Leasure NC, Berd D, Mastrangelo MJ: Taxol and tamoxifen (T and T) for metastatic melanoma [abstract]. Proc Am Soc Clin Oncol 1996, 15:432. This abstract reports encouraging second-line antitumor activity for this novel treatment combination. An alternative mechanism of action for tamoxifen. ie, modulation of drug resistance, is suggested.
22. Parkinson DR, Houghton AN, Mersey P. Borden EC: Biologic therapy for melanoma. In Cutaneous Melanoma. Edited by Balch CM, Houghton AN, Milton GW, Sober AJ, Soong SJ, Philadelphia: JB Lippincott Co.; 1992:522-541.
23. Mitchell M: Active specific immunotherapy of melanoma. Br Med Bull 1995, 51:631-646.
24. Argawala SS, Kirkwood JM: Interferons in melanoma. Curr Opin Oncol 1996, 8:167-174. This is an excellent review of the role of the interferon. particularly interferon alpha, in the treatment of various stages of malignant melanoma.
25. Sparano JA, Dutcher JP: Interleukin-2 for the treatment of advanced melanoma, Hematol Oncol Ann 1993, 1:279-285.
26. Royal RE, Steinberg SM, White D. el al:. Correlates of response to IL-2 therapy in patients treated for metastatic renal cancer and melanoma Cancer J Sci Am 1996, 6:91-98. This article reviews the vast NCI Surgery Branch experience with the use of high-dose interleukin-2 regimens to treat metastatic kidney cancer and melanoma. Tumor response in melanoma is correlated with disease restricted to subcutaneous tissue, the development of vitiligo and the amount of interleukin-2 delivered. It is notable that even in this population which all received high-dose interleukin-2, a potential dose-response relationship was observed.
27. Rubin JT, Day R, Duquesnoy R, Simonis B, Adams S. Lee J. Lotze MT: HLA-DQ1 is associated with clinical response and survival of patients with melanoma who are treated with interleukin-2. Ther Immunol 1995, 2:1-6.
28. Tartour E, Blay JY, Dorval T, Escudier B, Mosserie V, Douillard JY, Deneux L, Gorin I, Negrier S, Mathiot C, Pouillart P, Fridman WH: Predictors of clinical response to interleukin-2 based immunotherapy in melanoma patients: a French multiinstitutional study. J Clin Oncol 1996, 14:1697-1703. This article evaluated various potential predictors of response to interleukin-2 based therapy administered in a French multi-institutional setting. They determined that patients with high serum levels of c-reactive protein or visceral organ involvement were less likely to respond to interleukin-2 therapy. High serum interleukin-6 levels were also negatively correlated with response, but this was not an independent predictive variable.
29. Legha SS, Gianan MA, Plager C, Eton OE, Papadopoulous NE: Evaluation of interleukin-2 administered by continuous infusion in patients with metastatic melanoma. Cancer 1996, 77:89-96 This article describes the University of Texas MD Anderson Cancer Center experience with inpatient continuous infusion interleukin-2. They report a 22% response rate for this intramediate dose regimen with toxicity generally manage able on a regular inpatient ward. The median response duration, however, was only six months, a relatively short time compared with high-dose bolus inter leukin-2 regimens.
30. Margolin K: The clinical toxicities of high-dose interleukin-2. In Therapeutic Applications of Interleukin-2. Edited by Atkins MB, Mier JW. New York: Marcel Dekker; 1993:331-362.
31. Margolin K, Atkins M, Dutcher J, Sosman J, Weiss G, Lotze M, Singer J, Bianco J, Bakke L: Prospective randomized trial of lisophylline (CT1501 R) for the modulation of interleukin-2 (IL-2) toxicity [abstract]. Proc Am Soc Clin Oncol 1996, 15:725.
32. Trehu EG, Mier JW, DuBois JS, Sorce D, Klempner MS, Epstein M, Dinarello CA, Shapiro L, Kappler K, Ronayne L, Atkins MB: A phase I trial of interleukin-2 in combination with the soluble tumor necrosis factor receptor p75 IgG chimera (TNFR:Fc). Clin Cancer Res 1996, 2:1341-1351.
33. Du Bios JS, Trehu EG, Mier JW, Shapiro L, Epstein M, Klempner M, Dinarrello C, Kappler K, Ronayne L, Rand W, Atkins MB: Randomized placebo-controlled clinical trial of high-dose interleukin-2 (IL-2) in combination with the soluble TNF receptor IgG chimera (TNFR:Fc). J Clin Oncol 1997, in press. This randomized, placebo-controlled trial showed that the TNFR:Fc did not reduce the toxicity associated with high-dose interleukm-2, despite blocking the action of circulating tumor necrosis factor in a bioassay and inhibiting several biologic processes known to be associated with high-dose interleukin-2 therapy, Antitumor effects were maintained with an excellent response rate observed in the study patients with metastatic melanoma.
34. Rosenberg SA, Lotze MT, Yang JC, Linehan WM, Seipp C, Calabro S, Karp SE, Sherry RM, Steinberg S, White DE: Combination therapy with interleukin-2 and alpha-interferon for the treatment of patients with advanced cancer. J Clin Oncol 1989, 7:1863-1874.
35. Sparano JA, Fisher RI, Sunderland M, Margolin K, Ernest ML, Sznol M, Atkins MB, Dutcher JP, Micetich KC, Weiss GR, Dorosho JH, Aronson FR, Rubinstein LV, Mier JW: Randomized phase III trial of treatment with high-dose interleukin-2 either alone or in combination with interferon alfa-2a in patients with advanced melanoma. J Clin Oncol 1993, 11:1969-1977.
36. Eton O, Talpaz M, Lee KH, Rothberg JM, Brell JM, Benjamin RS: Phase II7 trial of recombinant human interleukin-2 and interferon-alpha 2a. Cancer 1996, 77:893-899. This article describes a phase II trial of inpatient continuous infusion interleukin-2 and intramuscular interferon alfa in patients with metastatic melanoma. A low response rate (8%) was observed for the combination regimen.
37. Kruit WH, Goey SH, Calabresi F, Lindemann A, Stahel RA, Poliwoda H, Osterwalder B, Stoter G: Final report of a phase II study of interleukin 2 and interferon alpha in patients with metastatic melanoma. Br J Cancer 1995, 71:1319-1321. This article describes a phase II evaluation of continuous infusion interleukin-2 and subcutaneous interferon alfa for patients with metastatic melanoma. A low response rate (14%) was observed with short median time to progression.
38. Keilholz U, Scheibenbogen C, Brossart P, Möhler T, Tilgen W, Hunstein W: Interleukin-2-based immunotherapy and chemoimmunotherapy in metastatic melanoma. Recent Results Cancer Res 1995, 139:383-390. This article describes the results of the "decrescendo" interleukin-2 and interferon regimen in patients with metastatic melanoma. A high response rate (31%) was again observed. They also examined secondary immune parameters associated with this regimen, when used alone or shortly after cytotoxic chemotherapy, and found them to be unaffected by the chemotherapy.
39. Margolin KA, Aronson F, Sznol M, Atkins MB, Gucalp R, Fisher RI, Sunderland M, Doroshow JH, Ernest ML, Mier JW, Dutcher JP, Gaynor ER, Weiss GR: Recombinant human IL-4 in advanced renal cancer and malignant melanoma. J Immunotherapy 1994, 15:147-153.
40. Whitehead RP, Unger J, Balcerzak SP, Goodwin JW, Rivkin SE, Flaherty LE, Sondak VK: Phase II trial of recombinant human interleukin-4 in patients with disseminated malignant melanoma: a Southwest Oncology Group (SWOG) study. Proc Am Soc Clin Oncol 1996, 15:438.
41. Sznol M, Mier J, Dutcher JP, Sosman JA, Weiss GR, Isaacs R, Margolin KA: A phase II trial of daily 1-hour intravenous infusion of interleukin-6 (rHuIL-6) for metastatic malignant melanoma (MM). Proc Am Soc Clin Oncol 1994, 13:396.
42. Atkins MB, Robertson MJ, Gordon MS, Lotze MT, Du Bois J, Ritz J, Sandler A, Edington HD, Sherman ML: Phase I evaluation of intravenous recombinant human interleukin-12 (RHIL-12) in patients with advanced malignancies. Proc Am Soc Clin Oncol 1996, 15:270, This abstract describes the biologic and clinical effects of intravenously administered recombinant human interleukm-12. The maximum tolerated dose for the schedule was determined. A tumor response was seen in one patient with melanoma treated at the highest dose level.
43. Del Vecchio M, Mortarini R, Rimassa L, Fowst C, Anichini A, Parmiani G, Cascinelli N, Bajetta E: Preliminary experience with rHu IL-12 in the treatment of metastatic melanoma [abstract]. Proc Am Soc Clin Oncol 1996, 15:25. This abstract describes the results of a phase II pilot study of subcutaneous recombinant human interleukin-12 in patients with metastatic melanoma. Three responses were reported in 10 melanoma patients. Follow-up was extremely short, so no information was provided on the durability of these responses.
44. Cohen: IL-12 deaths: explanation and a puzzle. Science 1995, 270:908. This commentary describes the exquisite schedule sensitivity of recombinant human interleukin-12, whereby a single dose of recombinant human interleukin-12 is able to desensitize a patient to the toxicity of subsequent therapy for a minimum of two weeks.
45. Minasian LM, Yao TJ, Steffens TA, Scheinberg DA, Williams L, Riedel E, Houghton AN, Chapman PB: A phase I study of anti-GD3 ganglioside monoclonal antibody R24 and recombinant human macrophage-colony stimulating factor in patients with metastatic melanoma. Cancer 1995, 75:2251-2257.
46. Albertini MR, Hank JA, Schiller JH, Borchert A, Huseby-Moore J, Gan J, Sondel PM: A phase IB trial of chimeric anti-GDA2 antibody (ch14.18) plus interleukin-2 (IL2) for melanoma. Proc Am Soc Clin Oncol 1996, 15:432.
47. Rosenberg SA: The immunotherapy of solid cancers based on cloning the genes encoding tumor-rejection antigens. Ann Rev Med 1996, 47:481-491. This article reviews the interactions between the cellular immune system and growing cancers. It describes the ability to isolate tumor infiltrating lymphocytes capable of recognizing specific melanoma tumor antigens and the progress in identifying and cloning the genes that encode these specific antigens. It describes animal experiments and early and proposed clinical trials involving adoptively transferred tumor infiltrating lymphocytes or active immunization with various immunodominant peptides present in the specific tumor antigens.
48. Falkson CI, Falkson G, Falkson HC: Improved results with the addition of Interferon alpha 2b to dacarbazine in the treatment of patients with metastatic malignant melanoma. J Clin Oncol 1991, 9:1403-1408.
49. Thompson D, Adena M, McLeod GRC. Interferon alfa-2a does not improve response or survival when combined with dacarbazine in metastatic malignant melanoma: results of a multi-institutional Australian randomized trial, QMP8704. Melanoma Res 1993. 3:133-138.
50. Bajetta E, DI Leo A, Zampmo M, Sertoli MR, Comella G, Barduagni, M, Gianotti B, Queirol P, Tribbia G, Bernengo MG: Multicenter randomized trial of dacarbazine alone or in combination with two different doses and schedules of Interferon alfa-2A in the treatment of advanced melanoma. J Clin Oncol 1994,12:806-811.
51. Kirkwood JM, Ernstoff MS, Giuliano A, Gams R, Robinson WA, Costanzi J, Pouillart P, Speyer J, Grimm M, Spiegel R: Interferon α-2a and dacar-bazine in melanoma. J Natl Cancer Inst 1990, 82:1062-1063.
52. Margolin KA, Doroshow JH, Akman SA, Leong LA, Morgan RJ, Somlo G, Raschko J, Pereira C, Yonemoto L, Ahn C: Phase II trial of cisplatin and α-interferon in advanced malignant melanoma. J Clin Oncol 1992. 10:1574-1578
53. Morton R, Cregan E, Schaid D, Kardinal CG, McCormick GW, McHall MS,Weisenfeld M: Phase III trial of recombinant leukocyte A Interferon (IFN-alpha-2a) plus 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and the combination cimetidine with BCNU in patients with disseminated malignant melanoma. Am J Clin Oncol (CCT) 1991, 14:152-155.
54. Smith K, Green J, Eccles J: Interferon alpha-2a and vindesine in the treatment of advanced malignant melanoma. Eur J Cancer 1992, 28:438-441.
55. O'Neill P, Hersh E, Warneke J, Ketcham M, Nichols H, MacNeil W: Phase II trial of combination chemotherapy and biological response modification in metastatic melanoma [abstract], Proc Am Soc Clin Oncol 1996, 15:432.
56. Flaherty LE, Liu PY, Fletcher WS, Goodwm JW, Balcerzak SP, Daniels D, Stephens RL, Sondak VK: Dacarbazine and outpatient interleukin-2 in treatment of metastatic malignant melanoma: a phase II Southwest Oncology Group trial. J Natl Cancer Inst 1992, 84:893-894.
57. Plager C, Papadopoulos NE, Gianan MA, Bedikian AY, Buzaid AC, Eton O, Legha SS, Benjamin RS: A pilot study of Interferon alfa-2b and cisplatin, velban and DTIC (CVD) in metastatic melanoma [abstract]. Proc Am Soc Clin Oncol 1996, 15:439.
58. Stoter G, Aamdal S, Rodenhuis S, Cleton FJ, Iacobelli S, Franks CR, Oskam R, Shiloni E: Sequential administration of recombinant human interleukin-2 and dacarbazine in metastatic melanoma: a multicenter phase II study. J Clin Oncol 1991, 9:1687-1691.
59. Richards JM, Mehta N, Ramming K, Skosey P: Sequential chemotherapy/immunotherapy for metastatic melanoma. J Clin Oncol 1992, 8:1338-1343.
60. Legha SS, Buzaid AC: Role of recombinant interleukin-2 in combination with interferon-alfa and chemotherapy in the treatment of advanced melanoma. Semin Oncol 1993, 2(suppl 9):27-32
61. Khayat D, Borel C, Tourani JM, Benhammouda A, Antoine E, Rixe O, Vuillemin E, Basex PA, Thill L, Franks R, Auclerc G, Soubrane C, Banzet P, Weil M: Sequential chemoimmunotherapy with cisplatin, interleukin-2 and Interferon alfa-2a for metastatic melanoma. J Clin Oncol 1993, 12:2173-2180.
62. Demchak PA, Mier JW, Robert NJ, O'Brien K, Gould JA, Atkins MB: Interleukin-2 and high-dose cisplatin in patients with metastatic melanoma: a pilot study. J Clin Oncol 1991, 9:1821-1830.
63. Atkins MB, O'Boyle KR, Sosman JA, Weiss GR, Margolin KA, Ernest ML, Kappler K, Mier JW, Sparano JA, Fisher RI, Eckardt JR, Pereira C, Aronson FR: Multi-institutional phase II trial of intensive combination chemoimmunotherapy for metastatic melanoma. J Clin Oncol 1994, 12:1553-1560.
64. Flaherty LE, Robinson W, Redman BG, Gonzales R, Martino S, Kraut M, Valdivieso M, Rudloph AR: A phase II study of dacarbazine and cisplatin in combination with outpatient administered interleukin-2 in metastatic malignant melanoma Cancer 1993, 71:3520-3525.
65. Legha S, Ring S, Eton C, Plager A, Buzaid A, Papadopolous N: Durable complete responses (CR's) in metastatic melanoma treated with biochemotherapy using cisplatin + vinblastine + DTIC (CVD) and IL-2 + interferon-alpha (IFN-α) [abstract]. Proc Am Soc Clin Oncol 1995, 14:412.
66. Anderson CM, Buzaid AC, Legha SS: Systemic treatments for advanced cutaneous melanoma. Oncology 1995, 9:11 49-1168. This is a comprehensive review of the systemic treatment options for metastatic melanoma with an emphasis on the recent MD Anderson Cancer Center experience with combination biochemotherapy including the concurrent biochemotherapy regimen.
67. Buzaid AC, Legha SS: Combination of chemotherapy with interleukin-2 and interferon-alfa for the treatment of advanced melanoma. Semin Oncol 1994,21:23-28.
68. . Keilholz U, Goey SH, Punt CJA, Proebstle T, Salzman R, Schadenforl D, •• Lienard D, Scheibenbogen C, Eggermont AMM: A randomized trial of IFNα/IL-2 with or without CDDP in advanced melanoma: an EORTC Melanoma Cooperative Group trial [abstract]. Proc Am Soc Clin Oncol 1996, 15:436. This abstract is a brief report on the results of this large randomized phase III trial comparing descrendo interleukin-2 and Interferon with and without cisplatin. The response rate was significantly higher on the cisplatin containing arm, but response duration was longer for interleukin-2/interferon and overall survival was no different. A "tail of the curve" analysis is incomplete. This study calls into question the value of combination biochemotherapy relative to either chemotherapy or IL-2 based immunotherapy.
69. Thompson J, Gold P, Fefer A: Outpatient chemo-immunotherapy for patients with metastatic melanoma [abstract]. Proc Am Soc Clin Oncol 1996, 15:433. This abstract describes the University of Washington experience with an outpatient combination biochemotherapy regimen. Their regimen appeared to be reasonably well-tolerated with nausea and vomiting being the major complication. Antitumor activity appeared to be equivalent to higher dose regimens, but the sample size was small and much of the data was still preliminary.
70. Atzpodien J, Lopez E, Hánninen, Kirchner H, Franzke A. Körfer A, Volkenandt M, Duensing S, Schombur A, Chaitchik S, Poliwoda H: Chemoimmunotherapy of advanced malignant melanoma: sequential administration of subcutaneous interleukin-2 and interferon-α after intravenous dacarbazine and carboplatin or intravenous dacarbazine, cisplatin, carmustine and tamoxifen. Eur J Cancer 1995, 31A:876-881
71. 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, 32A:730-733