MELANOMA
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Open trials in cutaneous malignant melanoma.
Rudenstam CM.
Eur J Surg Oncol, 22(2):128-30 1996 Apr.This article emphasizes that all studies conducted on large number of patients followed up for long periods of time failed to demonstrate a survival advantage in patients with melanoma treated with adjuvant therapies, compared to those treated with surgery alone.
The role of adjuvant therapy in melanoma management.
Barth A; Morton DL.
Cancer, 75(2 Suppl):726-34 1995 Jan 15.This article underlines that two decade of research in melanoma treatment failed to demonstrate a relapse-free and overall survival advantage in patients with stage II and stage III melanoma treated with adjuvant chemotherapy or levamisole, compared to those treated with surgery only. One trial that studied the efficacy of interferon-gamma was interrupted after patients in the treatment group demonstrated higher mortality rates that the control group.
Cutaneous malignant melanoma in Scotland: incidence, survival, and mortality, 1979-94.
The Scottish Melanoma Group.
MacKie RM, et al.
BMJ 1997 Nov 1;315(7116):1117-21.The results of this study show that overall mortality rates in patients with melanoma decreased by 12% from 1984 to 1990, and this decrease seems attributable to earlier detection and other unknown factors, but not to treatment. The study was conducted on 6288 patients who had been diagnosed with melanoma between 1979 and 1990. During this time frame, the incidence of melanoma approximately doubled in both men and women (from 3.5 to 7.8 new cases for 100,000 men per year, and from 6.8 to 12.3 new cases for 100,000 women per year). Mortality rates remained steady from 1979 to 1984, then decreased by 10% in men and by 6% in women during 1985-1987, due to an increased detection of early stage cancers, and again decreased slightly from 1987 to 1990. The reasons for this latter decline in mortality rates is unknown, but it is not attributed to treatment, since the only change in treatment modalities that occurred during this time was the introduction of a more conservative surgical approach to tumor removal.
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.
Keilholz U; et al.
J Clin Oncol, 15(7):2579-88 1997 Jul.The results of this study show that chemotherapy treatment with cisplatin does not prolong survival in patients with metastatic melanoma. The study was conducted on 138 patients with advanced melanoma who were divided in two groups: one group received interferon and interleukin-2 plus cisplatin, and the other received interferon and interleukin only. No differences in survival were detected between the two groups.
Adjuvant treatment in stage I and II malignant melanoma: a randomized trial between chemoimmunotherapy and immunotherapy.
Castel T; et al.
Dermatologica, 183(1):25-30 1991.The results of this study show that chemotherapy does not prolong survival in patients with early stage melanoma. Eighty-two patients were randomized to receive immunotherapy (with the bacillus Calmette-GuŽerin) only, or immunotherapy and chemotherapy. No differences in survival were observed between the two groups.
Recombinant interleukin-2-based treatments for advanced melanoma: the experience of the European Organization for Research and Treatment of Cancer Melanoma Cooperative Group.
Keilholz U; Stoter G; Punt CJ; Scheibenbogen C; Lejeune F; Eggermont AM Cancer J. Sci Am, 3 Suppl 1():S22-8 1997 Dec.This article presents current evidence on the role of chemotherapy in the management of patients with advanced melanoma. Single-agent or combination chemotherapy in patients with stage IV melanoma has shown to produce high rates of tumor responses (tumor shrinkage), but no improvement in overall survival. It has not yet been determined whether the toxicity of these regimens outweighs their potential (and yet to be proven) benefits.
Phase II trial of topotecan in malignant melanoma.
Kraut EH; Walker MJ; Staubus A; Gochnour D; Balcerzak SP.
Cancer Invest, 15(4):318-20 1997.This study assessed the effects of the anticancer drug topotecan in patients with advanced melanoma. Sixteen patients were enrolled in the trial. No tumor responses were observed. Severe toxicity occurred in 70% of patients.
Prospective randomized trial of the treatment of patients with metastatic melanoma using chemotherapy with cisplatin, dacarbazine, and tamoxifen alone or in combination with interleukin-2 and interferon alfa-2b.
Rosenberg SA, et al.
J Clin Oncol, 17(3):968-75 1999 Mar.This was a randomized study to determine whether the addition of immunotherapy to chemotherapy results in better tumor control in patients with advanced melanoma. One hundred-two patients were enrolled; 52 patients received chemotherapy only, and 50 patients received chemotherapy plus immunotherapy (interferon alpha and interleukin-2). Although tumor responses were observed more frequently in the chemo-immunotherapy group (44% vs. 27%), this group also experienced higher treatment-related toxicity and showed a trend of decreased survival. Both regimens produced tumor responses that were only partial and short lasting.
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.
Johnston SR; et al.
Br J Cancer, 77(8):1280-6 1998 Apr.The results of this randomized trial show that the addition of interleukin 2 and interferon 2 alpha to chemotherapy in patients with advanced melanoma does not result in prolonged relapse-free and overall survival, and is associated with a twofold increased rate of toxic reactions.
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.
Rusthoven JJ; et al.
J Clin Oncol, 14(7):2083-90 1996 Jul.The results of this double-blind placebo-controlled, randomized trial show that the addition of tamoxifen to chemotherapy does not improve rate of tumor response in patients with advanced melanoma.
Phase II trial of interleukin 1 alpha and indomethacin in treatment of metastatic melanoma.
Janik JE; et al.
J Natl Cancer Inst, 88(1):44-9 1996 Jan 3.The results of this study show that combination treatment with interleukin 1 alpha and indomethacin in patients with melanoma is associated with minimal tumor response (10%) and significant adverse effects.
Phase II trial of recombinant human interleukin-4 in patients with disseminated malignant melanoma: a Southwest Oncology Group study.
Whitehead RP; et al.
J Immunother, 21(6):440-6 1998 Nov.The results of this study show that interleukin 4 is not effective in the management of patients with advanced melanoma. Thirty-four patients were enrolled in the study. Tumor response was observed in only one patient (3%). Average survival was 6 months. Adverse effects included liver toxicity, nausea and vomiting, diarrhea, headache, fatigue, muscular and joint pains, edema, fever and chills.
Prophylactic isolated limb perfusion for localized, high-risk limb melanoma
Results of a multicenter randomized phase III trial. European Organization for Research and Treatment of Cancer Malignant Melanoma Cooperative Group Protocol 18832
The World Health Organization Melanoma Program Trial 15, and the North American Perfusion Group Southwest Oncology Group-8593.
Koops HS; et al.
J Clin Oncol, 16(9):2906-12 1998 Sep.The results of this study show that regional infusion of chemotherapy to the limb in proximity to a melanoma lesion in the attempt to reduce the risk of future tumor recurrences is associated with significant adverse events, and no benefits. Eight hundred thirty-two patients were enrolled in the study; 412 underwent surgery consisting of resection of the melanoma lesion, and 420 underwent surgery followed by isolated limb perfusion with the anticancer drug melphalan plus mild hyperthermia. Progression of disease and overall survival did not differ between the two groups. Toxicity (including two limb amputations) occurred significantly more often in patients who underwent chemotherapy compared to those who did not. These data do not support the use of adjuvant chemotherapy in the management of patients with early cancer.
Eastern cooperative group trial of interferon gamma in metastatic melanoma: an innovative study design.
Schiller JH; Pugh M; Kirkwood JM; Karp D; Larson M; Borden E.
Clin Cancer Res, 2(1):29-36 1996 Jan.The results of this study show that treatment with interferon gamma is ineffective in the management of patients with metastatic melanoma. Ninety-eight patients were enrolled in the study. Tumor responses were observed in 5% of patients and were of short duration. Toxicity included liver toxicity, fever and chills.
Dacarbazine-vindesine versus dacarbazine-vindesine-cisplatin in disseminated malignant melanoma.
A randomised phase III trial.
Jungnelius U; et al.
Eur J Cancer, 34(9):1368-74 1998 Aug.The results of this study show that the addition of cisplatin to a chemotherapy regimen consisting of dacarbazine and vindesine does not result in improved survival and adds significant toxicity in patients with advanced melanoma.
Phase II clinical trial of recombinant alpha 2b interferon and 13 cis retinoic acid in patients with metastatic melanoma.
Rosenthal MA; Oratz R.
Am J Clin Oncol, 21(4):352-4 1998 Aug.The results of this study show that treatment with interferon alpha and retinoic acid does not improve survival and causes significant toxicity in patients with metastatic melanoma. Thirteen patients were enrolled in the study. Tumor shrinkage was observed in one case. All patients experienced substantial fatigue, muscle pains, loss of appetite, and inflammation of the oral lining. Severe toxicity required 50% dose reduction in 7 patients, and interruption of treatment in another one.
Phase III trial of dacarbazine versus dacarbazine with interferon alpha-2b versus dacarbazine with tamoxifen versus dacarbazine with interferon alpha-2b and tamoxifen in patients with metastatic malignant melanoma
An Eastern Cooperative Oncology Group study.
Falkson CI; Ibrahim J; Kirkwood JM; Coates AS; Atkins MB; Blum RH.
J Clin Oncol, 16(5):1743-51 1998 May.The results of this study show that tamoxifen and interferon are ineffective in the treatment of patients with advanced melanoma. Two hundred fifty-eight patients were randomized to receive the anticancer drug dacarbazine in one of the following four regimens: dacarbazine only, dacarbazine plus tamoxifen, dacarbazine plus interferon, or dacarbazine plus both tamoxifen and interferon. No differences in survival were observed between the four groups, but patients receiving interferon experienced significantly more toxicity.
Interferon-alpha and chemohormonal therapy for patients with advanced melanoma
Final results of a phase I-II study of the Cancer Biotherapy Research Group and the Mid-Atlantic Oncology Program.
Stark JJ; et al.
Cancer, 82(9):1677-81 1998 May 1.The results of this study show that the addition of interferon alpha to combination chemotherapy in patients with advanced melanoma does not improve survival and is associated with severe toxicity.
A phase II study of carboplatin, cisplatin, interferon-alpha, and tamoxifen for patients with metastatic melanoma.
Gause BL; et al.
Cancer Invest, 16(6):374-80 1998.The results of this study show that combination treatment consisting of cisplatin, carboplatin, tamoxifen, and interferon-alpha in patients with advanced melanoma is associated with an 18% tumor response and with unacceptable toxicity.
The role of interleukin-2 in the management of stage IV melanoma
The EORTC melanoma cooperative group program.
Keilholz U, Eggermont AM.
Cancer J Sci Am 2000 Feb;6 Suppl 1:S99-103.This study reviewed the results of 27 trials conducted on 631 patients with advanced stage melanoma receiving combination treatment with interleukin (IL)-containing regimens. Administration of chemotherapy was not associated with improved outcome. The effects of IL2 on survival are still being evaluated in a trial that is currently under way.
Combined treatment with dacarbazine, cisplatin, fotemustine and tamoxifen in metastatic malignant melanoma.
Richard MA, et al.
Melanoma Res, 8(2):170-4 1998 Apr.The results of this trial, conducted on 20 patients with advanced stage melanoma, show that treatment with a combination chemotherapy regimen consisting of dacarbazine, cisplatin, fotemustine, and tamoxifen does not improve survival and causes significant toxicity, and is therefore not recommended in the management of this disease.
Phase II study of combined levamisole with recombinant interleukin-2 in patients with advanced malignant melanoma.
Creagan ET, et al.
Am J Clin Oncol, 20(5):490-2 1997 Oct.This study presents the results of a trial conducted on 19 patients with advanced melanoma enrolled to receive an experimental protocol consisting of levamisole and interleukin-2. No tumor responses were observed. Severe toxicity was observed in 5 patients. The authors conclude that this regimen should not be further tested on patients with malignant melanoma.
ALTERNATIVE MELANOMA TREATMENTS
Randomised trial of hyperthermia as adjuvant to radiotherapy for recurrent or metastatic malignant melanoma. European Society for Hyperthermic Oncology.
Overgaard J et al.
Lancet, 345(8949):540-3 1995 Mar 4.The results of this trial show that hyperthermia significantly increases tumor responses in patients with advanced melanoma, and has the potential of curing the disease in patients with few metastatic lesions. The study was conducted on 134 patients with advanced melanoma who were randomized to receive radiotherapy only or radiotherapy with hypertermia (a procedure were high heat is delivered to the patient, either locally or systemically). Hypertermia was the factor most significantly related to improved survival, even though, due to technical difficulties, the protocol goals were achieved in only 14% of heat-treatments. Heat-treatment was not associated with any increase in toxic reactions.
