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NCI CANCERLIT^® Search: Therapy of Melanoma - June 2002

National Cancer Institute^®
Last Modified: June 1, 2002

Endocrinologic changes in male patients with melanoma during interferon alfa-2b therapy.
Phase II trial of Paclitaxel and Dacarbazine with filgrastim administration in advanced malignant melanoma.
Biochemotherapy for advanced melanoma: maybe it is real.
A phage display selected fab fragment with MHC class I-restricted specificity for MAGE-A1 allows for retargeting of primary human T
Lymph-node metastases in patients with melanoma: what is the optimum management?
Comparison of the efficacy of two different dosage dacarbazine-based regimens and two regimens without dacarbazine in metastatic melanoma: a
U0126, a mitogen-activated protein kinase kinase inhibitor, inhibits the invasion of human A375 melanoma cells.
Vaccines for melanoma: translating basic immunology into new therapies.
Survival by radiation therapy oncology group recursive partitioning analysis class and treatment modality in patients with brain metastases
Two-week skin cancer referrals.
Thin melanomas and regression, thick melanomas and older men: prognostic implications and perspectives on secondary prevention.
Cytokine-mediated growth inhibition of human melanoma cells.
Humoral responses to melanoma vaccine, genetically modified with interleukin 6 and soluble interleukin 6 receptor.
Prognostic factors of overall survival in patients with delayed lymph node dissection for cutaneous malignant melanoma.
Prognostic factors in therapeutic lymphadenectomy in melanoma.
A new graphic for quality adjusted life years (Q-TWiST) survival analysis: the Q-TWiST plot.
Long-term freedom from recurrence in 2 stage IV melanoma patients following vaccination with tyrosinase peptides.
Current treatment of cutaneous melanoma and the sentinel lymph node.
Temozolomide plus thalidomide in patients with advanced melanoma: results of a dose-finding trial.
The Environmental Protection Agency's National SunWise School Program: sun protection education in US schools (1999-2000).
Incisional biopsy and melanoma prognosis.
Promotion of frequent tanning sessions by indoor tanning facilities: two studies.
Skin cancer screening by dermatologists: prevalence and barriers.
High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients
Rational development of peptide vaccination in clinical oncology.
Surgical margins for melanoma: is 2 cm too much?
Melanoma: margins for error.
Melanoma: Margins for error -- another view.
A plan to promote the prevention and early detection of melanoma.
Intraarterial chemotherapy of malignant melanoma metastatic to the liver.
Radiation therapy following nodal surgery for melanoma: an analysis of late toxicity.
Phase II study of paclitaxel and carboplatin for malignant melanoma.
Phase II trial of KW2189 in patients with advanced malignant melanoma.
New applications of cancer immunotherapy.
Interleukin-2: clinical applications.

1
UI - 11939829
AU - Weidinger SE; Hein R; Ring J; Kohn FM
TI - Endocrinologic changes in male patients with melanoma during interferon alfa-2b therapy.
SO - Arch Dermatol 2002 Apr;138(4):541-2

2
UI - 12025231
AU - Feun LG; Savaraj N; Hurley J; Marini A
TI - Phase II trial of Paclitaxel and Dacarbazine with filgrastim administration in advanced malignant melanoma.
SO - Cancer Invest 2002;20(3):357-61
AD - Sylvester Comprehensive Cancer Center, University of Miami, 1475 N.W. 12th Avenue, Miami, FL 33136, USA.
A Phase II trial was conducted in patients with advanced malignant melanoma with intravenous Paclitaxel and Dacarbazine (DTIC). The initial starting dose for Paclitaxel was 135 mg/m2 followed by DTIC 800 mg/m2. Due to the lack of myelosuppression and other toxicities, the starting dose for Paclitaxel was escalated to 250 mg/m2 and the dose for DTIC escalated to 1000 mg/m2. Twenty-five patients were enrolled in this study. Among the 25 patients assessable for response, three patients had a partial response with a response rate of 12% (CI 3-31%) and one patient had stable disease. Three additional patients showed evidence of anti-tumor activity with minor responses. For patients who had no prior chemotherapy or biochemotherapy, the response rate was 20%. Toxicity was generally tolerable and included mainly neurotoxicity from Paclitaxel. At the doses and schedule used, the combination of Paclitaxel and DTIC did not appear to increase the response rate compared to each agent used singly.

3
UI - 12011117
AU - Khayat D; Bernard-Marty C; Meric JB; Rixe O
TI - Biochemotherapy for advanced melanoma: maybe it is real.
SO - J Clin Oncol 2002 May 15;20(10):2411-4

4
UI - 11894998
AU - Willemsen RA; Debets R; Hart E; Hoogenboom HR; Bolhuis RL; Chames P
TI - A phage display selected fab fragment with MHC class I-restricted specificity for MAGE-A1 allows for retargeting of primary human T lymphocytes.
SO - Gene Ther 2001 Nov;8(21):1601-8
AD - Department of Clinical and Tumor Immunology, Academic Hospital Rotterdam/Daniel den Hoed Cancer Center, The Netherlands.
The clinical benefit of adoptive transfer of MHC-restricted cytotoxic T lymphocytes(CTL) for the treatment of cancer is hampered by the low success rate to generate antitumor CTLs. To bypass the need for tumor-specific CTL, we developed a strategy that allows for grafting of human T lymphocytes with MHC-restricted antigen specificity using in vitro selected human Fab fragments fused to the Fc(epsilon)RI-gamma signaling molecule. Retroviral introduction of a Fab-based chimeric receptor specific for MAGE-A1/HLA-A1 into primary human T lymphocytes resulted in binding of relevant peptide/MHC complexes. Transduced T lymphocytes responded to native MAGE-A1/HLA-A1POS target cells by specific cytokine production and cytolysis. Therefore, peptide/MHC-specific Fab fragments represent new alternatives to TCR to confer human T lymphocytes with tumor specificity, which provides a promising rationale for developing immunogene therapies.

5
UI - 11902552
AU - Fife K; Thompson JF
TI - Lymph-node metastases in patients with melanoma: what is the optimum management?
SO - Lancet Oncol 2001 Oct;2(10):614-21
AD - Addenbrooke's Hospital, Cambridge, UK.
Lymph-node metastasis is an indicator of poor prognosis for patients with melanoma. The management of regional nodes is controversial, with continuing debate about whether surgery or radiotherapy of positive lymph nodes improves long-term survival or whether nodal involvement is merely a marker of aggressive disease. However, there is general agreement that systemic chemotherapy is rarely an effective form of management. This review therefore considers surgical and radiotherapeutic aspects of lymph-node management in patients with melanoma. We discuss regional control and survival after lymph-node surgery in retrospective series, randomised trials of elective lymph-node dissection, the role of 'sentinel' lymph-node biopsy, radiobiology and radiotherapy fractionation issues in melanoma treatment, retrospective studies of adjuvant nodal radiotherapy, and finally, randomised trials of adjuvant radiotherapy after lymph-node dissection.

6
UI - 11828263
AU - Jelic S; Babovic N; Kovcin V; Milicevic N; Milanovic N; Popov I;
TI - Radosavljevic D Comparison of the efficacy of two different dosage dacarbazine-based regimens and two regimens without dacarbazine in metastatic melanoma: a single-centre randomized four-arm study.
SO - Melanoma Res 2002 Feb;12(1):91-8
AD - Institute for Oncology and Radiology of Serbia, Department of Medical Oncology, Pasterova 14, 11000 Belgrade, Yugoslavia. jelics@ncrc.ac.yu
The aim of this randomized four-arm phase III study was to evaluate whether there is a difference in activity between regimens containing dacarbazine and regimens without dacarbazine in metastatic melanoma, whether there is a dose-effect relationship for dacarbazine, and whether non-dacarbazine-containing aggressive regimens are in any way superior to non-aggressive ones. A total of 219 patients with metastatic cutaneous melanoma were included in this study; 196 of them were evaluable for activity. The patients were randomized into four treatment arms: arm A (standard dose dacarbazine arm), vincristine 1.4 mg/m2 on day 1, carmustine (BCNU) 60 mg/m2 on day 1, and dacarbazine 300 mg/m2 per 24 h on days 2-5; arm B (high-dose dacarbazine arm), vincristine and BCNU as in arm A and dacarbazine 600 mg/m2 per 24 h on days 2-5; arm C ('aggressive' regimen without dacarbazine), vindesine 3 mg/m2 on day 1, bleomycin 7 mg/m2 per 24 h on days 1-4, and cisplatin 30 mg/m2 per 24 h on days 5-8; arm D ('non-aggressive' regimen without dacarbazine), BCNU 100 mg/m2 on day 1 and procarbazine 90 mg/m2 per 24 h on days 1-10. The four arms were well balanced with regard to patient- and disease-related characteristics. On an intend-to-treat basis, the response rate was 11 out of 49 (22%) in arm A, nine out of 47 (19%) in arm B, 16 out of 63 (25%) in arm C and nine out of 60 (15%) in arm D. There was a large overlap between the 95% confidence intervals and no significant differences in the response rates between the four arms. Median survival in the four treatment arms was 4, 5, 6 and 4 months, respectively, again with no significant differences. Median survival for responders (8, 11, 10 and 13 months, respectively) in all four arms was significantly longer than in non-responders (4, 3, 5 and 4 months, respectively). Arms A, B and C were significantly more toxic compared with arm D, which was for all practical purposes devoid of toxicities. The efficacy of all four regimens thus appeared comparable both in terms of response rate and survival. Responders in all four arms achieved a survival benefit. There does not seem to be a dose-effect relationship for dacarbazine in metastatic melanoma. Chemotherapy from arm D, might be well suited for 'fragile' or elderly patients due to the lack of toxicity.

7
UI - 11888667
AU - Ge X; Fu YM; Meadows GG
TI - U0126, a mitogen-activated protein kinase kinase inhibitor, inhibits the invasion of human A375 melanoma cells.
SO - Cancer Lett 2002 May 28;179(2):133-40
AD - The Cancer Prevention and Research Center, Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman, WA 99164-6510, USA.
The anti-invasive ability of the mitogen-activated protein kinase (MAPK) kinase inhibitor, U0126, was examined in human A375 melanoma cells in vitro. The effect was compared to that of PD98059, another commonly used MEK (MAPK kinase) inhibitor. U0126 or PD98059 showed a dose-dependent inhibition of A375 cell invasion through growth factor-reduced Matrigel. U0126 was more potent than PD98059 in suppressing tumor cell invasion. Both compounds significantly decreased urokinase plasminogen activator (uPA) and matrix metalloproteinases-9 (MMP-9) concentrations in conditioned media. At 5 microM, U0126 inhibited phosphorylation of the MEK 1/2 to a non-detectable level within 24 h. The phosphorylation of extracellular signal-related kinase 1/2 was also dramatically suppressed by the treatment with 10 microM U0126 or 40 microM PD98059. Both compounds suppressed the protein expression of c-Jun, but not c-Fos. The expression of uPA and MMP-9 was also inhibited. Our data suggest that U0126 is an effective agent in inhibiting human A375 melanoma cell invasion and that the effect is partially due to the decreased production of uPA and MMP-9.

8
UI - 11905765
AU - Wolchok JD; Livingston PO
TI - Vaccines for melanoma: translating basic immunology into new therapies.
SO - Lancet Oncol 2001 Apr;2(4):205-11
AD - Clinical Immunology Service, Hematologic Department of Medicine, Memorial Sloan-Kettering Cancer Center, NY 10021, USA.
Advances in molecular biology and immunology in the past 10-15 years have allowed for a greater understanding of the molecules present on melanoma cells that are recognised by the immune system. The rising incidence of melanoma, combined with lack of efficacy of cytotoxic therapies, means there is a significant need for the development of effective immunotherapies. We discuss three types of vaccine for melanoma, which are currently in phase III clinical trials: allogeneic and autologous cellular vaccines, and carbohydrate vaccines. We also discuss several new areas of vaccine development, including DNA vaccines, dendritic-cell-based vaccines, peptide vaccines, and heat-shock protein vaccines. Although initial clinical trials have shown the safety and immunological efficacy of vaccines for melanoma, the true clinical benefit of these strategies will only be revealed in large randomised trials.

9
UI - 12001126
AU - Buchsbaum JC; Suh JH; Lee SY; Chidel MA; Greskovich JF; Barnett GH
TI - Survival by radiation therapy oncology group recursive partitioning analysis class and treatment modality in patients with brain metastases from malignant melanoma: a retrospective study.
SO - Cancer 2002 Apr 15;94(8):2265-72
AD - Department of Radiation Oncology, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
BACKGROUND: In a population of patients with brain metastases from melanoma, the authors sought to determine whether various therapies provided any benefit at all, whether local therapy was better than whole brain radiotherapy (WBRT), and whether combined local therapy and WBRT provided any advantage over local therapy alone. They also analyzed survival according to a Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) to determine how well the RTOG RPA classes predicted survival in this patient population and whether treatments varied in effectiveness from category to category. METHODS: A total of 74 patients with brain metastases from melanoma were treated at The Cleveland Clinic Foundation between 1984 and 1998. For this study, the authors reviewed patient charts and confirmed survival status. Survival was compared by treatment modality (surgical resection, WBRT, stereotactic radiosurgery, or WBRT combined with local therapy). Survival also was compared according to the RTOG RPA prognostic classes (Class 1, Class 2, or Class 3), which has not been validated previously in patients with malignant melanoma. RESULTS: The median survival was 5.5 months for all patients. Survival varied significantly by RTOG prognostic class; The median survival was 10.5 months (range, 2.2-99.2 months) for patients in Class 1, 5.9 months (range, 0.2-43.9 months) for patients in Class 2, and 1.8 months (range, 0.1-6.9 months) for patients in Class 3 (P < 0.0001). Survival analysis showed that combined treatment offered significantly better survival (P < 0.0001; combined vs. other). The median survival was 8.8 months (range, 1.8-99.2 months) for the combined therapy group, 4.8 months (range, 1.2-27.8 months) for the local therapy alone group, 2.3 months (range, 0.2-9.6 months) for the WBRT alone group, and 1.1 months (0.1-3.0 months) for the group that received no therapy. CONCLUSIONS: Adding WBRT to local therapy may improve survival in this group of patients: Combined therapy was superior to WBRT alone. The RPA classification scheme likely has prognostic value for patients with brain metastases from malignant melanoma. Prospective studies are required to overcome selection bias and confirm these results. Copyright 2002 American Cancer Society.

10
UI - 11952715
AU - Morgan C; Robertshaw H; Cooper H; Keohane S
TI - Two-week skin cancer referrals.
SO - Clin Exp Dermatol 2002 Mar;27(2):164

11
UI - 12020232
AU - Demierre MF
TI - Thin melanomas and regression, thick melanomas and older men: prognostic implications and perspectives on secondary prevention.
SO - Arch Dermatol 2002 May;138(5):678-82

12
UI - 11774562
AU - Kortylewski M; Heinrich PC; Mackiewicz A; Behrmann I
TI - Cytokine-mediated growth inhibition of human melanoma cells.
SO - Adv Exp Med Biol 2001;495():169-72
AD - Department of Biochemistry, RWTH Aachen, Germany.

13
UI - 11774603
AU - Nawrocki S; Laciak M; Izycki D; Gryska K; Wysocki PJ; Grabarczyk P;
TI - Karczewska A; Kaczmarek A; Murawa P; Malicki J; Rose-John S; Mackiewicz A Humoral responses to melanoma vaccine, genetically modified with interleukin 6 and soluble interleukin 6 receptor.
SO - Adv Exp Med Biol 2001;495():411-8
AD - GreatPoland Cancer Centre, Garbary 15, Poznan, Poland.

14
UI - 11095410
AU - Kretschmer L; Preusser KP; Marsch WC; Neumann C
TI - Prognostic factors of overall survival in patients with delayed lymph node dissection for cutaneous malignant melanoma.
SO - Melanoma Res 2000 Oct;10(5):483-9
AD - Abteilung fur Dermatologie und Venerologie, Georg-August-Universitat Gottingen, Germany.
To date, no study of melanoma patients who have undergone delayed lymph node dissection (DLND) has focused on the independent prognostic factors of overall survival, as calculated from surgery on the primary. Using Kaplan-Meier estimates and Cox's proportional hazard model, the significance of prognostic factors was evaluated in 173 patients who developed clinically apparent regional lymph node metastases. When calculated from excision of the primary tumour (median Breslow thickness 3.0 mm), the median survival was 38 months. When calculated from DLND, the median survival was 19 months. Multifactorial analysis revealed that the number of nodes involved at the time of DLND significantly affected both survival calculated from primary tumour excision (P = 0.0002) and survival calculated from DLND (P < 0.0001). In contrast, the well-known risk factors of primary melanoma did not significantly influence overall survival or survival after DLND. However, the remission duration between surgery on the primary and DLND clearly depended on epidermal ulceration (P = 0.001), Breslow thickness (P = 0.009) and the site of the primary melanoma (P = 0.048). Thus, in patients submitted to DLND, the risk factors of primary melanoma influence the early period of the disease, until metastatic lymph nodes become palpable. With regard to overall survival, only the extent of nodal disease determines the prognosis of these patients.

15
UI - 11468522
AU - Retsas S
TI - Prognostic factors in therapeutic lymphadenectomy in melanoma.
SO - Melanoma Res 2001 Jun;11(3):315-8

16
UI - 12003054
AU - Sloan JA; Sargent DJ; Lindman J; Allmer C; Vargas-Chanes D; Creagan ET;
TI - Bonner JA; O'Connell MJ; Dalton RJ; Rowland KM; Brooks BJ; Laurie JA A new graphic for quality adjusted life years (Q-TWiST) survival analysis: the Q-TWiST plot.
SO - Qual Life Res 2002 Feb;11(1):37-45
AD - Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. jsloan@mayo.edu
One of the challenges of interpreting a Quality-adjusted time without symptoms of disease and toxicity (Q-TWiST) analysis is examining the sensitivity of conclusions that may be drawn to varying values of the utility coefficients for days with toxicity and days after disease progression. We present a graphic that parsimoniously displays the impact on median Q-TWiST survival across treatment groups of varying values of the utility coefficients. The goal of the graphic is to present a concise Q-TWiST analysis. We use Zhao and Tsiatis (Biometrika 1997; 84(2): 339-348) to adjust for the bias in Kaplan-Meier (K-M) estimates. The graphic contains bounds that approximate points for which statistical significance would be achieved by comparing the median Q-TWiST survival between treatment alternatives for each value of the utility coefficients. The plot may be generalized to compare Q-TWiST means, medians or percentiles across treatment groups. We demonstrate the application of the Q-TWiST plot through a re-analysis of a randomized phase III North Central Cancer Treatment Group (NCCTG) clinical trial of recombinant Interferon-2alpha in patients with malignant melanoma. We explore alternative options to customize the graphic representation for other data sets drawn from several NCCTG clinical trials.

17
UI - 11992409
AU - Scheibenbogen C; Nagorsen D; Seliger B; Schmittel A; Letsch A; Bauer S;
TI - Max N; Bock M; Atkins D; Thiel E; Keilholz U Long-term freedom from recurrence in 2 stage IV melanoma patients following vaccination with tyrosinase peptides.
SO - Int J Cancer 2002 May 20;99(3):403-8
AD - Medizinische Klinik III, Hamatologie, Onkologie und Transfusionsmedizin, Universitatsklinikum Benjamin-Franklin, Freie Universitat Berlin, Berlin, Germany.
We report here on 2 patients who received adjuvant vaccination with an HLA-A2- or HLA-A24-restricted tyrosinase peptide, respectively, and GM-CSF for frequently relapsing stage IV melanoma. Following resection of metastases and irradiation of brain metastases in 1 patient, both patients were without evidence of disease when receiving the first vaccination. While the patients had had 9 and 12, respectively, mostly s.c., relapses during the 3 years before vaccination, they experienced freedom from relapse for more than 2 years after vaccination. We found a T-cell response to the vaccine peptide in both patients in the peripheral blood by ex vivo IFN-gamma ELISPOT assay. The T-cell population could be further characterized by 4-color flow cytometry in 1 patient, showing that the majority of the peptide-specific CD3(+)CD8(+)IFN-gamma(+) T cells were granzyme B-positive and CCR-7-negative, characterizing them as effector T cells with the ability to mediate cytotoxicity and migrate to inflamed tissues. In this patient also, augmentation of the T-cell response to autologous tumor cells by vaccination could be detected. A single-site postvaccination relapse occurred in both patients, showing downregulation of tyrosinase expression in 1 patient, while normal expression levels for tyrosinase, MHC class I antigens and components of the antigen-processing machinery were found in the other patient. These results suggest that peptide vaccination resulted in a prolonged relapse-free interval in these high-risk patients. Copyright 2002 Wiley-Liss, Inc.

18
UI - 12043108
AU - Bruns SD; McGee JM; Phillips JW
TI - Current treatment of cutaneous melanoma and the sentinel lymph node.
SO - J Okla State Med Assoc 2002 May;95(5):332-5
AD - University of Oklahoma-Tulsa, Schustermann Health Sciences Center, Oklahoma, USA.

19
UI - 12039921
AU - Hwu WJ; Krown SE; Panageas KS; Menell JH; Chapman PB; Livingston PO;
TI - Williams LJ; Quinn CJ; Houghton AN Temozolomide plus thalidomide in patients with advanced melanoma: results of a dose-finding trial.
SO - J Clin Oncol 2002 Jun 1;20(11):2610-5
AD - Departments of Medicine, Epidemiology and Biostatistics, and Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. hwuw@mskcc.org
PURPOSE: To establish a safe and tolerated regimen of an oral cytotoxic agent, temozolomide, and a cytostatic agent, thalidomide, in patients with unresectable stage III or IV malignant melanoma. PATIENTS AND METHODS: Patients with unresectable stage III or IV melanoma without brain metastases were entered successively onto four treatment cohorts: level 1, temozolomide 50 mg/m(2)/d for 6 weeks followed by a 4-week break; levels 2, 3, and 4, temozolomide 75 mg/m(2)/d for 6 weeks followed, respectively, by breaks of 4, 3, and 2 weeks. Thalidomide was started at 200 mg/d, and escalated to a maximum dose of 400 mg/d. Safety was assessed at weeks 2 and 4 and every 4 weeks thereafter; tumor response was evaluated every 8 to 10 weeks. RESULTS: Twelve patients were enrolled, three on each cohort. Therapy was generally well tolerated on all of the treatment schedules. Thalidomide at a dose of 400 mg/d was well tolerated in patients younger than 70, and 200 mg/d was well tolerated in older patients. The most common adverse events were grade 2 or 3 constipation and neuropathy, which were attributed to thalidomide. Five major responses (one complete, four partial) were documented, all at dose levels 2 to 4. Three of the five responding patients were in the over-70 age group. The median duration of response was 6 months (range, 4 to 17+ months), and the median overall survival was 12.3 months (range, 4 to 19+ months). CONCLUSION: The combination of temozolomide and thalidomide was well tolerated and had antitumor activity in patients with advanced melanoma, including elderly patients over 70 years old.

20
UI - 12004307
AU - Geller AC; Cantor M; Miller DR; Kenausis K; Rosseel K; Rutsch L; Brooks
TI - DR; Zhang Z; Demierre MF The Environmental Protection Agency's National SunWise School Program: sun protection education in US schools (1999-2000).
SO - J Am Acad Dermatol 2002 May;46(5):683-9
AD - Department of Dermatology, Boston University School of Medicine, Boston, MA 02118, USA.
BACKGROUND: Melanoma, the most fatal form of skin cancer, is rising at a rate faster than that of all preventable cancers except lung cancer in the United States. Childhood exposure to ultraviolet (UV) light increases the risk for skin cancer as an adult; thus starting positive sun protection habits early may be key to reducing incidence. METHODS: We evaluated the US Environmental Protection Agency's SunWise School Program, a national, environmental education program for sun safety of children in primary and secondary schools (kindergarten through eighth grade). The program was evaluated with surveys administered to participating students. An identical 18-question, self-administered survey was completed by students (median age, 10 years) in the classroom before and immediately after the SunWise educational program. RESULTS: Surveys were completed by students in 40 schools before (pretests; n = 1894) and after the program was presented (post-tests; n = 1815). Significant improvement was noted for the 3 knowledge variables: appropriate type of sunscreen to be used for outdoor play, highest UV Index number, and need for hats and shirts outside. Intentions to play in the shade increased from 73% to 78% (P <.001), with more modest changes in intentions to use sunscreen. Attitudes regarding healthiness of a tan also decreased significantly. CONCLUSIONS: Brief, standardized sun protection education can be efficiently interwoven into school health education and result in improvements in knowledge and positive intentions for sun protection.

21
UI - 12004308
AU - Bong JL; Herd RM; Hunter JA
TI - Incisional biopsy and melanoma prognosis.
SO - J Am Acad Dermatol 2002 May;46(5):690-4
AD - Departments of Dermatology, Western Infirmary, Glasgow, UK. JanLB1997@aol.com
BACKGROUND: There are many circumstances in clinical practice in which it is helpful to have a definitive diagnosis of melanoma before subjecting a patient to mutilating surgery. Previous studies on the effect of incisional biopsy on melanoma prognosis were conflicting and lacked a matched control group to account for the other prognostic indicators. OBJECTIVE: We set up this study to investigate the effect of incisional biopsy on melanoma prognosis. METHODS: The design was of a retrospective case control. Data were obtained from the database of the Scottish Melanoma Group; the database was set up in 1979 to collect detailed clinical, pathologic, and follow-up data on all patients diagnosed with melanoma in Scotland. Each incisional case was matched against 2 excision cases controlling for age, sex, sites, and Breslow thickness. The main outcome measures were time from initial biopsy to recurrence and to melanoma-related death. RESULTS: Two hundred sixty-five patients who had incisional biopsy before definitive excision of melanoma were included in the study; these were matched with 496 cases of excisional biopsy specimens. Cox's proportional hazard model for survival analysis showed that biopsy type had no significant effect on recurrence (P =.30) or melanoma-related death (P =.34). CONCLUSIONS: This study is the largest series on the effect of incisional biopsy on melanoma prognosis to date and the first to include matched controls. Melanoma prognosis is not influenced by incisional biopsy,. before definitive excision.

22
UI - 12004310
AU - Kwon HT; Mayer JA; Walker KK; Yu H; Lewis EC; Belch GE
TI - Promotion of frequent tanning sessions by indoor tanning facilities: two studies.
SO - J Am Acad Dermatol 2002 May;46(5):700-5
AD - Graduate School of Public Health, San Diego State University, CA 92182, USA.
BACKGROUND: Indoor tanning may increase the risk of melanoma and other health problems. Frequent users of indoor tanning facilities may be at particularly high risk. OBJECTIVE: In study 1 our purpose was to assess the prevalence and nature of indoor tanning advertisements; in study 2 we aimed to assess tanning facility compliance to recommended exposure schedules. METHODS: In study 1, tanning facility advertisements over a 4-month period from 24 San Diego County newspapers were monitored. In study 2, we assessed compliance with recommended exposure schedules via a telephone interview of 60 San Diego County tanning facilities. RESULTS: Approximately 75% of the indoor tanning advertisements promoted unlimited tanning. Only 5% of facilities were in compliance with recommended tanning schedules, and 100% offered "unlimited" tanning packages. CONCLUSIONS: These findings suggest that the indoor tanning industry, through pricing incentives that allow frequent sessions, may be promoting overexposure to UVR. Stronger legislation is needed to address this issue.

24
UI - 11331315
AU - Kirkwood JM; Ibrahim JG; Sosman JA; Sondak VK; Agarwala SS; Ernstoff MS;
TI - Rao U High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIB-III melanoma: results of intergroup trial E1694/S9512/C509801.
SO - J Clin Oncol 2001 May 1;19(9):2370-80
AD - Division of Hematology-Oncology and Department of Pathology, Department of Medicine, University of Pittsburgh Cancer Institute Melanoma Center, University of Pittsburgh Medical Center, Pittsburgh, PA 15213-2582, USA. jmk@jiimmy.harvard.edu
PURPOSE: Vaccine alternatives to high-dose interferon alfa-2b therapy (HDI), the current standard adjuvant therapy for high-risk melanoma, are of interest because of toxicity associated with HDI. The GM2 ganglioside is a well-defined melanoma antigen, and anti-GM2 antibodies have been associated with improved prognosis. We conducted a prospective, randomized, intergroup trial to evaluate the efficacy of HDI for 1 year versus vaccination with GM2 conjugated to keyhole limpet hemocyanin and administered with QS-21 (GMK) for 96 weeks (weekly x 4 then every 12 weeks x 8). PATIENTS AND METHODS: Eligible patients had resected stage IIB/III melanoma. Patients were stratified by sex and number of positive nodes. Primary end points were relapse-free survival (RFS) and overall survival (OS). RESULTS: Eight hundred eighty patients were randomized (440 per treatment group); 774 patients were eligible for efficacy analysis. The trial was closed after interim analysis indicated inferiority of GMK compared with HDI. For eligible patients, HDI provided a statistically significant RFS benefit (hazard ratio [HR] = 1.47, P = .0015) and OS benefit (HR = 1.52, P = .009) for GMK versus HDI. Similar benefit was observed in the intent-to-treat analysis (RFS HR = 1.49; OS HR = 1.38). HDI was associated with a treatment benefit in all subsets of patients with zero to > or = four positive nodes, but the greatest benefit was observed in the node-negative subset (RFS HR = 2.07; OS HR = 2.71 [eligible population]). Antibody responses to GM2 (ie, titers > or = 1:80) at days 29, 85, 365, and 720 were associated with a trend toward improved RFS and OS (P2 = .068 at day 29). CONCLUSION: This trial demonstrated a significant treatment benefit of HDI versus GMK in terms of RFS and OS in melanoma patients at high risk of recurrence.

25
UI - 11476074
AU - Keiholz U; Scheibenbogen C; Theil E; Schadendorf D
TI - Rational development of peptide vaccination in clinical oncology.
SO - Onkologie 2001 Apr;24(2):174

26
UI - 11982507
AU - Balch CM
TI - Surgical margins for melanoma: is 2 cm too much?
SO - ANZ J Surg 2002 Apr;72(4):251-2

27
UI - 11982522
AU - Heenan PJ
TI - Melanoma: margins for error.
SO - ANZ J Surg 2002 Apr;72(4):300-3

28
UI - 11982523
AU - McCarthy WH
TI - Melanoma: Margins for error -- another view.
SO - ANZ J Surg 2002 Apr;72(4):304-6

29
UI - 11912790
AU - Harris J
TI - A plan to promote the prevention and early detection of melanoma.
SO - Dermatol Nurs 2000 Oct;12(5):329-33
AD - Washington Hospital Center, Washington, DC, USA.
Malignant melanoma will affect millions of Americans in the year 2000 and its incidence is rising 7% per year (Skin Cancer Foundation, 1992). Numerous programs have been developed in various parts of the country to control the rate of increase, with mixed results. Public education programs can potentially prevent skin cancers and promote early detection of melanoma. An innovative prevention and detection program involving schools, pediatricians, nurses, and state agencies that will target those who are at risk for developing melanoma and skin cancer was developed by the author as a new mechanism by which the public can be educated regarding this disease.

30
UI - 11813606
AU - Melichar B; Dvorak J; Jandik P; Touskova M; Solichova D; Megancova J;
TI - Voboril Z Intraarterial chemotherapy of malignant melanoma metastatic to the liver.
SO - Hepatogastroenterology 2001 Nov-Dec;48(42):1711-5
AD - Department of Oncology & Radiotherapy, Charles University Medical School & Teaching Hospital, Building 23, 500 05 Hradec Kralove, Czech Republic. melichar@fnhk.cz
BACKGROUND/AIMS: The prognosis of malignant melanoma metastatic to the liver is poor. The aim of the present report was to analyze retrospectively the effectiveness of regional chemotherapy and biologic therapy in patients with hepatic metastases of malignant melanoma. METHODOLOGY: Seven patients with hepatic metastases of malignant melanoma were treated by intraarterial administration of the combination of cisplatin, vinblastine and dacarbazine, or melphalan, with or without interleukin-2, interferon-alpha and interferon-gamma. RESULTS: The median survival of 4 patients with metastatic involvement initially limited to the liver is 19+ months in contrast to a median survival of 5 months in patients with concurrent extrahepatic disease. Intraarterial administration of cytokines led to an initial decrease in circulating lymphocyte numbers, with subsequent return to pretreatment levels, and to an increase in urinary neopterin, a marker of immune activation. CONCLUSIONS: Regional intraarterial administration of chemotherapy with or without cytokines may be effective for controlling hepatic metastases of malignant melanoma in patients with disease limited to the liver, but little benefit is evident in patients who present with concurrent extrahepatic disease.

31
UI - 12028092
AU - Burmeister BH; Smithers BM; Davis S; Spry N; Johnson C; Krawitz H;
TI - Baumann KC Radiation therapy following nodal surgery for melanoma: an analysis of late toxicity.
SO - ANZ J Surg 2002 May;72(5):344-8
AD - Queensland Radium Institute, South Brisbane, Australia. B.Burmeister@mailbox.uq.edu.au
BACKGROUND: The role of adjuvant radiation therapy following resection of malignant melanoma involving regional lymph nodes remains controversial. There is no published randomized trial comparing surgery alone to surgery with postoperative radiation therapy that shows a benefit in terms of local control. Some retrospective studies, however, suggest that radiation given postoperatively reduces local recurrence. One of the obstacles to patients routinely being offered radiation therapy is the concern over the added late toxicity that may occur. The present article is a report of the first 130 patients of a prospective phase II multicentre study in Australia and New Zealand. METHODS: The study was aimed at patients who had had a resection of melanoma in regional nodes or in a regional node basin. The patients were given adjuvant radiation therapy to a recommended dose of 48 Gy in 20 fractions over 4 weeks using accepted radiation techniques for each of the major node sites. This report describes the late toxicity of the treatment received by these patients. RESULTS: The results of late toxicity experienced in the study were acceptable. CONCLUSION: The regimen of radiation therapy used could form the basis for the treatment arm of a randomized trial.

32
UI - 12040289
AU - Hodi FS; Soiffer RJ; Clark J; Finkelstein DM; Haluska FG
TI - Phase II study of paclitaxel and carboplatin for malignant melanoma.
SO - Am J Clin Oncol 2002 Jun;25(3):283-6
AD - Adult Oncology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Conventional chemotherapy in the treatment of malignant melanoma has been disappointingly ineffective. Although the most active single agent is dacarbazine, numerous trials support the activity of platinum analogs against melanoma. Several recent trials also demonstrate the single-agent activity of paclitaxel, and support the administration of these agents together in the treatment of a number of solid tumors. We conducted a phase II study treating patients with metastatic melanoma with paclitaxel as a 3-hour infusion of 175 mg/m2, and carboplatin dosed to yield an area under the curve of 7.5 administered during 30 minutes. Patients were previously untreated or treated once with a regimen not including a platinum or taxane agent and had a performance status of 0 or 1. Seventeen patients (8 males; 9 females; average age 51) were enrolled. Thirty-three percent of patients had disease involving the skin, 40% lungs, 33% lymph nodes, 26% liver, and 13% other visceral organs. Anaphylactic reactions developed in two patients associated with paclitaxel infusion, and the patients were subsequently taken off the study. Of the 15 remaining patients, 3 (20%) had partial responses, 7 (47%) had stable disease, and 5 (33%) showed evidence of progressive disease. Eleven patients experienced grade III or IV hematologic toxicity. All treatment-related toxicities were reversible. There were no treatment-related deaths. The combination of paclitaxel and carboplatin has moderate activity against malignant melanoma, with expected reversible hematologic toxicities. Although not prospectively compared with single agents, the combination of paclitaxel and carboplatin may be a treatment option for some patients. Comparisons with other treatment regimens and the search for additional active compounds against melanoma are needed.

33
UI - 12040295
AU - Markovic SN; Suman VJ; Vukov AM; Fitch TR; Hillman DW; Adjei AA; Alberts
TI - SR; Kaur JS; Braich TA; Leitch JM; Creagan ET Phase II trial of KW2189 in patients with advanced malignant melanoma.
SO - Am J Clin Oncol 2002 Jun;25(3):308-12
AD - Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA.
KW-2189, a semisynthetic duocarmycine antibiotic has been shown to exert antiproliferative effects against human tumor cell lines in vitro and animal tumor models in vivo. Phase I studies identified myelosuppression as the most noteworthy adverse effect. Presented are two concurrent phase II studies assessing the antitumor and toxicity profile of KW-2189 in metastatic melanoma patients. One of the studies accrued patients with a history of prior melanoma therapy and the other accrued patients without a history of prior melanoma therapy. KW-2189 was administered at 0.4 mg/m2 to previously treated patients and 0.5 mg/m2 to the previously untreated. Treatment was administered intravenously on day 1 of a 6-week cycle. Thirty previously untreated and 15 previously treated patients were accrued. The toxicity profiles of the both groups of patients were similar. Of the 15 previously treated patients, 8 completed once cycle of treatment, 2 completed 2 cycles, and 5 completed 3 cycles. Dose modification for neutropenia/ thrombocytopenia was necessary in six patients. Among the previously untreated cohort (30 patients), 16 completed 1 cycle, 5 completed 2 cycles, 4 completed 3 cycles, 3 completed 4 cycles, and 2 completed 6 cycles. Doses were modified (neutropenia or thrombocytopenia) in 11 patients. None of the 15 previously treated patients responded to therapy. Four patients remained stable during two cycles. Five of the previously untreated patients achieved a partial remission/regression. Response duration ranged from 2.8 to 16.6 months. Overall objective response rate was 17%. Regarding survival, one previously treated patient is still alive 2.9 years after study entry, and three previously untreated patients are still alive 1.6, 2.3, and 2.9 years after study entry. The 1-year survival rate for previously treated patients is 27% and for the untreated patients is 23%. In summary, the lack of significant antitumor activity of KW-2189 and its associated toxicity suggest that further testing of this regimen in patients with stage IV melanoma is not warranted.

34
UI - 12068381
AU - Agarwala SS
TI - New applications of cancer immunotherapy.
SO - Semin Oncol 2002 Jun;29(3 Suppl 7):1-4
AD - Melanoma Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213-2582, USA.

35
UI - 12068383
AU - Atkins MB
TI - Interleukin-2: clinical applications.
SO - Semin Oncol 2002 Jun;29(3 Suppl 7):12-7
AD - Cutaneous Oncology & Biologic Therapy Programs, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Interleukin-2 (IL-2) is a promising immunotherapeutic agent for the treatment of metastatic melanoma, acute myelogenous leukemia, and metastatic renal cell carcinoma. While high-dose IL-2 regimens have shown clinical benefit in the treatment of melanoma and renal cell carcinoma, serious dose-limiting toxicities have limited their clinical use in a broader group of patients. Low-dose IL-2 therapy has produced disappointing clinical response rates in melanoma. While the response rates to low-dose IL-2 have been better in renal cell carcinoma, the quality of these responses relative to those seen with high-dose IL-2 therapy remains a concern. The addition of IL-2 to chemotherapeutic regimens (biochemotherapy) has been associated with overall response rates of up to 60% in patients with metastatic melanoma, but this has yet to be translated into a confirmed improvement in survival. It remains to be determined whether further modifications of IL-2-based regimens or the addition of newer agents to IL-2 will produce better tumor response and survival. Copyright 2002, Elsevier Science (USA). All rights reserved.

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