National Cancer Institute®
Last Modified: November 21, 2001
UI - 21249764
AU - Wildemore JK 4th; Schuchter L; Mick R; Synnestvedt M; Elenitsas R;
TI - Bedrosian I; Czerniecki BJ; Guerry D 4th; Lessin SR; Elder DE; Bucky LP Locally recurrent malignant melanoma characteristics and outcomes: a single-institution study.
SO - Ann Plast Surg 2001 May;46(5):488-94
AD - Department of Surgery, University of Pennsylvania Medical Center, Philadelphia, USA.
Despite improvements in the identification and treatment of melanoma, local recurrence continues to challenge the success of current melanoma therapy. A retrospective analysis of 1,996 patients presenting from 1990 to 1997 at the Pigmented Lesion Group of the University of Pennsylvania was performed to assess clinical characteristics and outcomes of locally recurrent melanoma. The cases were analyzed by chart and pathological slide review. A control group was identified for statistical comparison. The incidence of locally recurrent melanoma during the study period was 2.2%. Lentigo maligna melanoma (LMM) accounted for 37% of the local recurrences. Increased tumor thickness and microsatellites were associated with "early" local recurrence and decreased survival from time of recurrence. Nineteen percent of the local recurrences occurred more than 5 years after the initial definitive treatment. The preponderance of locally recurrent LMM suggests the need for refinements in the techniques of margin identification and surgical excision of LMM. Tumors with increased thickness and microsatellites should receive particularly close attention. Lastly, with nearly 20% of the local recurrences occurring more than 5 years after the initial date of treatment, the authors suggest extending the follow-up time for all melanoma lesions beyond 5 years.
UI - 21271574
AU - Ooi BS; Eu KW; Seow-Choen F
TI - Primary anorectal malignant melanoma: clinical features and results of surgical therapy in Singapore--a case series.
SO - Ann Acad Med Singapore 2001 Mar;30(2):203-5
AD - Department of Colorectal Surgery, Singapore General Hospital, 1 Hospital Drive, Singapore 169608.
INTRODUCTION: Primary malignant melanoma arising from the anorectum is uncommon. The natural history of anorectal malignant melanoma is that of a very poor prognosis with early dissemination of disease. Successful surgical treatment has been rare. The present series reviews the clinical features and results of surgical management of patients with anorectal malignant melanoma treated in the Department of Colorectal Surgery, Singapore General Hospital. MATERIALS AND METHODS: Data for all patients treated for anorectal malignant melanoma during an 11-year period from 1989 to 1999 were reviewed. The age, sex, presenting symptoms, duration of symptoms prior to diagnosis, size of tumour, extent of disease, type of surgery and length of survival were analysed. RESULTS: Four men and 2 women, ranging in age from 31 to 81 years with histologically proven primary anorectal malignant melanoma, were included in the study. The most common (67%) presenting symptom was rectal bleeding. The mean tumour size was 2.5 cm (range 1 to 5 cm). All underwent abdomino-perineal resection. Three died of disseminated disease within 17 months while the other 3 were still alive at the time of this study; the longest up to 6.5 years from the time of diagnosis. CONCLUSION: The prognosis of primary anorectal malignant melanoma is poor. However, it is worthwhile treating aggressively as long-term survivor may be encountered in some.
UI - 21274622
AU - Carucci JA
TI - Treatment of lentigo maligna.
SO - Cutis 2001 May;67(5):389-92
AD - Department of Dermatology, Weill Medical College of Cornell University, 525 E 68th St, New York, NY 10021, USA.
Lentigo maligna (LM) is an indolent form of melanoma in situ with the potential to progress to invasive melanoma. Early detection and adequate treatment prior to development to invasive melanoma are essential. Definitive excision with negative margins is currently the treatment of choice for LM. Conventional excision, Mohs micrographic surgical excision, and nonexcisional methods of treatment of LM will be discussed.
UI - 21274623
AU - Silverberg NB
TI - Update on malignant melanoma in children.
SO - Cutis 2001 May;67(5):393-6
AD - Department of Dermatology, St. Luke's-Roosevelt Hospital Center, 1090 Amsterdam Ave, Suite 11D, New York, NY 10025, USA. firstname.lastname@example.org
Malignant melanoma is a rare event in children. Yet, the overall incidence has consistently risen in the past 20 years. Thus, the likelihood that our pediatric patients will develop malignant melanoma is increasing. Previously, the bulk of lesions were estimated to occur in children with large congenital melanocytic nevi. Recent reports, however, have highlighted new risk factors for malignant melanoma in children, while demystifying other entities previously believed to have a grave prognosis. Knowledge of risk factors and participation in public health efforts toward prevention and early intervention can help the practitioner protect pediatric patients from this malignancy.
UI - 21328265
AU - Tullio A; Bianchi B; Sesenna E
TI - [Lymphatic metastases in the parotid region from malignant skin neoplasm of the head: considerations for surgical treatment based on personal clinical experience]
SO - Acta Otorhinolaryngol Ital 2001 Feb;21(1):44-9
AD - Cattedra e Divisione di Chirurgia Maxillo-Facciale, Universita ed Ospedale di Parma.
The present paper considers some of the problems linked to the surgical treatment of parotid metastases. The authors base these considerations on their limited personal cases and on the most accredited literature. In the presence of cutaneous malignancies of the upper portion of the face, accurate clinical-radiological evaluation must be made of the parotid and neck region. Elective parotidectomy is performed when the cutaneous carcinoma is quite extensive or located in proximity of the gland or when the case involves a melanoma. Depending on the oncological margins, a sub-total parotidectomy may be enough; however, the facial nerve must be sacrificed if there is a clinical deficit or if it is directly affected by the tumor. As the dimensions of the neoplasm increase, the feasibility of saving the nerve decreases. Prophylactic treatment of the neck is advisable in parotid metastases from cutaneous malignancies, particularly melanoma. Nevertheless, it is possible to perform a selective dissection, avoiding the V level of the neck as the incidence of its involvement is quite low. Prognosis for these tumors is extremely poor. Of the eleven patients surgically treated, only 4 (36%) survived: 2 passed away from other causes not involved in the base pathology; 2 for distant metastases but with no signs of local recurrence and 1 other for recurrence of the primary pathology in the maxillary sinus mucosa. There is no difference in the survival of the two main histological groups: 2 out of 3 of the patients with melanoma (67%) died as did 3 out of 5 (60%) of those with epidermal carcinoma. This does not, obviously, include the two patients who died from other causes.
UI - 21439108
AU - Buzaid AC; Atkins M
TI - Practical guidelines for the management of biochemotherapy-related toxicity in melanoma.
SO - Clin Cancer Res 2001 Sep;7(9):2611-9
AD - Oncology Center, Hospital Sirio-Libanes, Sao Paulo, SP 01308-050, Brazil. email@example.com
The combination of cisplatin-based chemotherapy with interleukin 2 (IL-2) and IFN-alpha, referred to as biochemotherapy or chemoimmunotherapy, has shown promising antitumor activity in patients with metastatic melanoma. Phase II studies have reported overall response rates ranging from 40 to 60%, with durable complete remissions in approximately 10% of the patients. Toxicity, however, is often severe and can be life-threatening if the healthcare team is not familiar with toxicity management. In this report, we briefly describe the clinical results of the most effective biochemotherapy regimens and provide a detailed description and management of the most common toxic effects, with emphasis on the concurrent biochemotherapy program initially developed at M. D. Anderson Cancer Center and currently being tested in a slightly modified version in two large-scale Intergroup Phase III trials.
UI - 21443206
AU - Dubois RW; Swetter SM; Atkins M; McMasters K; Halbert R; Miller SJ;
TI - Shiell R; Kirkwood J Developing indications for the use of sentinel lymph node biopsy and adjuvant high-dose interferon alfa-2b in melanoma.
SO - Arch Dermatol 2001 Sep;137(9):1217-24
AD - Protocare Sciences Inc, Santa Monica, USA. firstname.lastname@example.org
OBJECTIVES: To convene a multidisciplinary panel of dermatologists, surgical oncologists, and medical oncologists to formally review available data on the sentinel lymph node (SLN) biopsy procedure and high-dose adjuvant interferon alfa-2b therapy for patients with melanoma and to rate the "appropriateness," "inappropriateness," or "uncertainty" of the procedure and therapy to guide clinical decision making in practice. PARTICIPANTS: The panel comprised 13 specialists (4 dermatologists, 4 oncologists, and 5 surgeons) from geographically diverse areas who practiced in community-based settings (n = 8) and academic institutions (n = 5). Participants were chosen based on recommendations from the relevant specialty organizations. EVIDENCE: A formal literature review was conducted by investigators at Protocare Sciences Inc, Santa Monica, Calif, on the risks and benefits of performing an SLN biopsy in patients with stage I or II melanoma and adjuvant interferon alfa-2b therapy in patients with stage II or III and supplemental information was obtained from various cancer societies and cancer research groups. Panel participants were queried on additional sources of relevant information. Unpublished, presented data were included in abstract form on 1 recently closed clinical trial. CONSENSUS PROCESS: The RAND/UCLA Appropriateness Method was used to review and rate multiple clinical scenarios for the use of SLN biopsy and interferon alfa-2b therapy. The consensus method did not force agreement. CONCLUSIONS: The panel rated 104 clinical scenarios and concluded that the SLN biopsy procedure was appropriate for primary melanomas deeper than 1.0 mm and for tumors 1 mm or less when histologic ulceration was present and/or classified as Clark level 4 or higher. The SLN biopsy was deemed inappropriate for nonulcerated Clark level 2 or 3 melanomas 0.75 mm or less in depth and uncertain in tumors 0.76 to 1.0 mm deep unless they were ulcerated or Clark level 4 or higher. Interferon alfa-2b therapy was deemed appropriate for patients with regional nodal and/or in-transit metastasis and for node-negative patients with primary melanomas deeper than 4 mm. The panel considered the use of interferon alfa-2b therapy uncertain in patients with ulcerated intermediate primary tumors (2.01-4.0 mm in depth) and inappropriate for node-negative patients with nonulcerated tumors less than 4.0 mm deep. Specialty-specific ratings were conducted as well.
UI - 21443825
AU - Lee P; Wang F; Kuniyoshi J; Rubio V; Stuges T; Groshen S; Gee C; Lau R;
TI - Jeffery G; Margolin K; Marty V; Weber J Effects of interleukin-12 on the immune response to a multipeptide vaccine for resected metastatic melanoma.
SO - J Clin Oncol 2001 Sep 15;19(18):3836-47
AD - Department of Medicine, Division of Medical Oncology, Keck/University of Southern California School of Medicine, Los Angeles, USA.
PURPOSE: Forty-eight patients with high-risk re-sected stage III or IV melanoma were immunized with two tumor antigen epitope peptides derived from gp100(209-217)(210M) (IMDQVPSFV) and tyrosinase(368-376)(370D) (YMDGTMSQV) emulsified with incomplete Freund's adjuvant (IFA). Patients received peptides/IFA with or without interleukin (IL)-12 30 ng/kg to evaluate the toxicities and immune responses in either arm with time to relapse and survival as secondary end points. PATIENTS AND METHODS: Immunizations were administered every 2 weeks for 8 weeks, then every 4 weeks for 12 weeks, and then once 8 weeks later. A leukapheresis to obtain peripheral-blood mononuclear cells for immune analyses was done before and after vaccination. Skin testing with peptides and recall reagents was performed before and after vaccinations. RESULTS: Local pain and granuloma formation, fever, and lethargy of grade 1 or 2 were observed. Transient vaccine-related grade 3-but no grade 4-toxicity was observed. Thirty-four of 40 patients developed a positive skin test response to the gp100 peptide but none to tyrosinase. Immune responses were measured by release of gamma-interferon in an enzyme-linked immunosorbent assay (ELISA) by effector cells in the presence of peptide-pulsed antigen-presenting cells or by an antigen-specific tetramer flow cytometry assay. Thirty-three of 38 patients demonstrated an immune response by ELISA after vaccination, as did 37 of 42 patients by tetramer assay. Twenty-four of 48 patients relapsed with a median follow-up of 20 months, and 10 patients in this high-risk group have died. CONCLUSION: These data suggest a significant proportion of patients with resected melanoma mount an antigen-specific immune response against a peptide vaccine and indicate that IL-12 may increase the immune response and supporting further development of IL-12 as a vaccine adjuvant.
UI - 21423023
AU - Kikuchi A; Nieda M; Schmidt C; Koezuka Y; Ishihara S; Ishikawa Y;
TI - Tadokoro K; Durrant S; Boyd A; Juji T; Nicol A In vitro anti-tumour activity of alpha-galactosylceramide-stimulated human invariant Valpha24+NKT cells against melanoma.
SO - Br J Cancer 2001 Sep 1;85(5):741-6
AD - Department of Research, The Japanese Red Cross Central Blood Center, 4-1-31 Hiroo, Shibuya-ku, Tokyo, 150-0012, Japan.
alpha-galactosylceramide (KRN 7000, alpha-GalCer) has shown potent in vivo anti-tumour activity in mice, including against melanoma and the highly specific effect of inducing proliferation and activation of human Valpha24+NKT-cells. We hypothesized that human Valpha24+NKT-cells activated by alpha-GalCer might exhibit anti-tumour activity against human melanoma. To investigate this, Valpha24+NKT-cells were generated from the peripheral blood of patients with melanoma after stimulation with alpha-GalCer pulsed monocyte-derived dendritic cells (Mo-DCs). Valpha24+NKT-cells did not exhibit cytolytic activity against the primary autologous or allogeneic melanoma cell lines tested. However, proliferation of the melanoma cell lines was markedly suppressed by co-culture with activated Valpha24+NKT-cells (mean +/- SD inhibition of proliferation 63.9 +/- 1.3%). Culture supernatants of activated Valpha24+NKT-cell cultures stimulated with alpha-GalCer pulsed Mo-DCs exhibited similar antiproliferative activities against melanoma cells, indicating that the majority of the inhibitory effects were due to soluble mediators rather than direct cell-to-cell interactions. This effect was predominantly due to release of IFN-gamma, and to a lesser extent IL-12. Other cytokines, including IL-4 and IL-10, were released but these cytokines had less antiproliferative effects. These in vitro results show that Valpha24+NKT-cells stimulated by alpha-GalCer-pulsed Mo-DCs have anti-tumour activities against human melanoma through antiproliferative effects exerted by soluble mediators rather than cytolytic effects as observed against some other tumours. Induction of local cytokine release by activated Valpha24+NKT-cells may contribute to clinical anti-tumour effects of alpha-GalCer. Copyright 2001 Cancer Research Campaign.
UI - 21468605
AU - Gonzalez-Larriba JL; Serrano S; Alvarez-Mon M; Camacho F; Casado MA;
TI - Diaz-Perez JL; Diaz-Rubio E; Fosbrook L; Guillem V; Lopez-Lopez JJ; Moreno-Nogueira JA; Toribio J Cost-effectiveness analysis of interferon as adjuvant therapy in high-risk melanoma patients in Spain.
SO - Eur J Cancer 2000 Dec;36(18):2344-52
AD - Department of Medical Oncology, Hospital Clinico San Carlos, Madrid, Spain. email@example.com
In the randomised clinical trial E1684, the administration of interferon (IFN) alpha-2b resulted in prolonged disease-free and overall survival in high-risk melanoma patients following surgical resection. However, and considering the cost and toxicity of IFN, the convenience of its widespread use should be evaluated. The aim of this study was to analyse the cost-effectiveness ratio of adjuvant therapy with IFN alpha-2b in melanoma patients versus an untreated control group. A Markov model was used to compare two hypothetical cohorts of 1000 patients aged 50 years, according to the clinical outcome of the E1684 study. The cohort of patients treated with IFN alpha-2b has an increased overall survival of 1.90 years during the patient's lifetime. The incremental discounted cost per life year gained of IFN versus observation is 9015 Euros according to the projection generated by the model. The sensitivity analysis demonstrated that changes in the most relevant study end-points do not modify the study outcome. In conclusion, in high-risk melanoma patients following surgical resection, the cost-effectiveness of IFN alpha-2b (at a dose of 20 MU/m2/day, 5 days per week for one month, followed by 10 MU/m2 TIW, up to one complete year of therapy) versus an untreated control group is within the limits established in health economics to determine if adoption of a new treatment is economically justified and is comparable with other interventions in which cost-effectiveness is acceptable to the National Health System.
UI - 21190900
AU - Atkins MB; Redman B; Mier J; Gollob J; Weber J; Sosman J; MacPherson BL;
TI - Plasse T A phase I study of CNI-1493, an inhibitor of cytokine release, in combination with high-dose interleukin-2 in patients with renal cancer and melanoma.
SO - Clin Cancer Res 2001 Mar;7(3):486-92
AD - Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
CNI-1493, an inhibitor of proinflammatory cytokines, was studied in a Phase I trial in melanoma and renal cancer patients receiving high-dose interleukin 2 (IL-2). Objectives of the study were to define the maximum tolerated dose (MTD) and toxicity of CNI-1493, to assess its pharmacological effects, and to define its pharmacokinetics. Twenty-four patients were treated in sequential cohorts with CNI-1493 doses from 2 through 32 mg/m2 daily. Patients first received only CNI-1493 daily for 5 days. After a 9-day rest, patients received two 5-day courses of IL-2 of 600,000 IU/kg every 8 h for up to 14 doses/course plus daily CNI-1493; courses were separated by a 9-day rest period. CNI-1493 administered alone was well tolerated at doses through 32 mg/m2; MTD was not reached. The only clinical toxicity attributed to CNI-1493 was occasional injection-site phlebitis. Grade 1 creatinine increases occurred in 1 of 7 patients at 4 mg/m2, in 1 of 1 patients at 25 mg/m2, and in 3 of 6 patients at 32 mg/m2 CNI-1493 alone. In combination with high-dose IL-2, CNI-1493 at > or = 25 mg/m2 seemed to exacerbate IL-2-induced nephrotoxicity: grade 3 or 4 creatinine increases developed in 3 of 6 patients at 25 or 32 mg/m2, as compared with 1 of 16 patients at doses < or = 16 mg/m2. The MTD for CNI-1493 given with high-dose IL-2 was 16 mg/m2. The dose-limiting toxicity of IL-2 was hypotension in 63% of patients; overall tolerance to IL-2 was not improved by CNI-1493. However, relative to changes seen in a reference group receiving high-dose IL-2 alone, at doses > or = 4 mg/m2 CNI-1493 did show evidence of pharmacological activity as an inhibitor of tumor necrosis factor production.
UI - 21262954
AU - Ribuffo D; Cavalieri L; De Vita F; Massa R; Prosperi D; Tuccimei M;
TI - Scuderi N Current role of immunoscintigraphy in malignant melanoma follow-up. A study of 114 patients.
SO - J Exp Clin Cancer Res 2001 Mar;20(1):11-5
AD - Division of Plastic Surgery, Nuclear Medicine Section, La Sapienza University, Rome, Italy.
Although its role and importance is debated, Immunoscintigraphy (IS) remains a popular technique in Malignant Melanoma (MM) follow-up for consecutive patients underwent 650 IS examinations at our Department. follow-up of at least 7 years are given here. IS results were compared to physical examination, to other imaging modalities and, where available, to histology. IS specificity and sensivity, concerning detection of melanoma metastases in lymph nodes, skin, brain, lung, visceral sites and bone, ranged from 37.5% and 22% to 100%. Our results indicate a high diagnostic accuracy of IS only for lymph node examination, but not for other possible locations of melanoma metastases. In our experience IS cannot be recommended for staging of melanoma patients, and should only be used in association with other imaging modalities.
UI - 21453549
AU - Lentsch EJ; Myers JN
TI - Melanoma of the head and neck: current concepts in diagnosis and management.
SO - Laryngoscope 2001 Jul;111(7):1209-22
AD - Department of Head and Neck Surgery, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
UI - 21424850
AU - Viar V
TI - Advances in surgical treatment of melanoma.
SO - Nurs Clin North Am 2001 Sep;36(3):507-15, x
AD - Division of Surgical Oncology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA. firstname.lastname@example.org
Malignant melanoma is fatal in one-fifth of the patients who are diagnosed with the disease. It is a solid tumor cancer that spreads primarily through lymph nodes, making it amenable to surgical treatment. Surgical interventions for melanoma that have developed over the years include diagnostic biopsy, wide excision, lymph node staging, and treatment of local and visceral metastases. Lymphatic mapping and sentinel lymph node biopsy are two important surgical approaches that are gaining favor over more traditional nodal staging. The use of reverse transcriptase-polymerase chain reaction (RT-PCR) to diagnose submicroscopic disease shows promise for staging patients at the earliest possible time. Multicenter, randomized clinical trials such as the Sunbelt Melanoma Trial are vital in answering the question of how best to treat early metastatic melanoma.
UI - 21453500
AU - Cascinelli N; Belli F; MacKie RM; Santinami M; Bufalino R; Morabito A
TI - Effect of long-term adjuvant therapy with interferon alpha-2a in patients with regional node metastases from cutaneous melanoma: a randomised trial.
SO - Lancet 2001 Sep 15;358(9285):866-9
AD - National Cancer Institute, Via G Venezian 1, 20133, Milan, Italy. email@example.com
BACKGROUND: Less than half of patients with melanoma that has spread to local draining regional lymph nodes (stage III melanoma) live with no disease for 5 years or longer after surgery. We aimed to see whether interferon alpha-2a increased survival prospects in these patients. METHODS: 444 patients from 23 centres in the WHO Melanoma Programme had complete lymphadenectomy for pathologically proven regional nodal spread of melanoma and were randomly assigned to receive either 3 MU subcutaneously of recombinant interferon alpha-2a three times a week for 3 years, or to observation alone after surgery. Patients were stratified by centre, nodes with macroscopic or microscopic melanoma, number of affected nodes, and nodal metastatic spread. Treatment was continued for 3 years or until first sign of relapse. FINDINGS: 424 patients entered the study. 5-year disease-free survival of those who had surgery plus interferon alpha-2a was 27.5% (95% CI 21.7-33.6); for those who received surgery alone, survival was 28.4% (22.5-34.6) (p=0.50). Neither Kaplan-Meier cumulative survival rates, nor multivariate analysis of survival, showed a difference between those who had surgery and interferon alpha-2a (35%, 95% CI 29-42) and those who had surgery alone (37%, 31-44). INTERPRETATION: Patients with melanoma that has spread to the local draining regional lymph nodes tolerate well 3 MU of interferon alpha-2a given subcutaneously three times a week for 3 years, but this treatment does not improve either disease-free or overall survival.
UI - 21460579
AU - Smith C; Cerundolo V
TI - Immunotherapy of melanoma.
SO - Immunology 2001 Sep;104(1):1-7
AD - Institute of Molecular Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
UI - 20208343
AU - Scheibenbogen C; Schmittel A; Keilholz U; Allgauer T; Hofmann U; Max R;
TI - Thiel E; Schadendorf D Phase 2 trial of vaccination with tyrosinase peptides and granulocyte-macrophage colony-stimulating factor in patients with metastatic melanoma.
SO - J Immunother 2000 Mar-Apr;23(2):275-81
AD - Universitatsklinikum Benjamin-Franklin, Medizinische Klinik III (Hamatologie, Onkologie and Transfusionsmedizin), Freie Universitat Berlin, Germany.
This phase II study was performed to determine the induction of a specific T-cell response, the clinical response rate, and toxicity of vaccination with different HLA class I-binding peptide epitopes derived from the melanocyte differentiation antigen tyrosinase in patients with stage IV melanoma. The study population consisted of 16 patients with metastatic disease and two patients who were macroscopically free of disease at study entry after resection of recurrent skin lesions. Patients received intradermal injections of 200 microgram [corrected] peptide corresponding to their HLA type on day 3, and 75 or 150 microg granulocyte-macrophage colony-stimulating factor on days 1 to 4. Vaccinations were repeated at weeks 2, 4, 6, 10, and 14. Monitoring of peptide-specific T-cell frequencies in the peripheral blood was performed using an interferon gamma ELISPOT assay. Eleven of the 16 patients with metastatic disease went off the protocol within the first 10 weeks because of tumor progression. Of the five patients with metastatic disease who received all six vaccinations, one patient showed a mixed response with regression of some lung metastases; two patients with progressive disease before vaccination had stable disease for 6 and 18+ months; and two patients had progression of their disease. The two patients who had all their metastases resected before vaccination did not have relapses for 6 and 12+ months after vaccination. Induction of tyrosinase-reactive T cells was found in these two patients and in two others with metastatic disease, including the one who achieved a mixed response and one with stable disease. This study shows limited clinical and immunologic activity of HLA class 1-peptide vaccination in combination with granulocyte-macrophage colony-stimulating factor in stage IV melanoma patients.
UI - 21369211
AU - Bondar' GV; Psaras GG; Zolotukhin SE
TI - [Treatment of colonic melanoma]
SO - Klin Khir 2001 Jan;(1):38-40
The results of treatment of 5 patients with colonic melanoma are presented. Fine-needle biopsy was used for morphological verification diagnosis. It was established that the patients with colonic melanoma are hospitalized in specialized department, as a rule, with nonopertable tumor. In 1 patient explorative laparotomy was done. Conduction of radical operative intervention was impossible because of presence of multiple metastases in liver. In 4 patients conservative treatment was performed. It was not possible to perform radical operation because of the process spreading. The patients life span after conduction of conservative therapy have constituted 14.5 mo at average.
UI - 21372390
AU - Guven K; Kittler H; Wolff K; Pehamberger H
TI - Cisplatin and carboplatin combination as second-line chemotherapy in dacarbazine-resistant melanoma patients.
SO - Melanoma Res 2001 Aug;11(4):411-5
AD - Division of General Dermatology, Department of Dermatology, University of Vienna Medical School, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. firstname.lastname@example.org
High-dose cisplatin regimens have been shown to be highly active in advanced melanoma patients but are associated with unacceptable side effects. In order to increase the platinum dose but avoid severe side effects, we treated 15 dacarbazine (DTIC)-resistant metastatic melanoma patients with a combination regimen of cisplatin (100 mg/m2) and carboplatin (200 mg/m2), two platinum analogues with a similar mode of action but a different toxicity pattern. After a mean follow-up period of 10.7 months (range 4-18 months), two patients (13.3%) achieved complete remission and two patients (13.3%) showed partial remission, giving an overall response rate of 26.4% (95% confidence interval [CI] 4.2-49%). Furthermore, three patients (20%; 95% CI 0-40.2%) experienced stable disease. The median duration of response was 7.1 months (95% CI 4.2-10.0 months), and the median overall survival was 12.5 months (95% CI 5.8-19.2 months), with eight patients still alive. The main side effects were haematological (leukopenia/thrombocytopenia World Health Organization [WHO] grade I-IV; anaemia WHO grade I-III), gastrointestinal (WHO grade I-III), neurological (WHO grade I-II) and renal (WHO grade I) toxicity. Nevertheless, except in one patient, side effects did not result in discontinuation of therapy. Despite the small number of patients treated in this preliminary study, we believe that combining cisplatin and carboplatin represents a novel, active and well-tolerated therapeutic option as second-line chemotherapy in DTIC-resistant advanced melanoma patients.
UI - 21381723
AU - Stopeck AT; Jones A; Hersh EM; Thompson JA; Finucane DM; Gutheil JC;
TI - Gonzalez R Phase II study of direct intralesional gene transfer of allovectin-7, an HLA-B7/beta2-microglobulin DNA-liposome complex, in patients with metastatic melanoma.
SO - Clin Cancer Res 2001 Aug;7(8):2285-91
AD - Arizona Cancer Center, 1515 North Campbell Avenue, Tucson, AZ 85724, USA. email@example.com
Cutaneous melanoma is one of the most rapidly increasing cancers in the United States. Because of the lack of effective treatment options and toxicities of most chemotherapeutic and radiation regimes, immunotherapies such as vaccination therapy represent an attractive approach for patients with advanced melanoma. The purpose of this study was to evaluate the response rate, time to progression, and survival of patients with metastatic melanoma treated by direct intratumoral injection with Allovectin-7 (a plasmid DNA encoding the genes HLA-B7 and beta2-microglobulin complexed with a cationic lipid mixture, DMRIE/DOPE. Fifty-two patients with metastatic melanoma were enrolled in this Phase II study. Therapy consisted of six intratumoral injections of 10 microg of Allovectin-7 over a 9-week period. Treatment was well tolerated. Treatment-related adverse events were mild to moderate, the most frequent of which were ecchymosis, pruritus (and/or discomfort at the injection site), and pneumothoraces. Regression of the injected lesion was observed in 18% of patients, including one complete response, three partial responses, and five minor responses. An overall response rate of 4% (two partial responses) was documented, and nine patients (18%) maintained stable disease for at least 11 weeks. Six patients remained alive 25.1 to 39.4 months from their first injection, including two patients with local (injected tumor) responses and one patient with an overall disease partial response. This study demonstrates that intratumoral administration of Allovectin-7 in metastatic melanoma is safe and can produce both responses in injected lesions and in overall disease. Clinical trials optimizing patient selection and combining Allovectin-7 with other modalities of therapy are currently ongoing in an effort to improve response rates.
UI - 21426655
AU - Wolf R; Wolf D; Morganti P; Ruocco V
TI - Sunscreens.
SO - Clin Dermatol 2001 Jul-Aug;19(4):452-9
AD - Department of Dermatology, Tel-Aviv Sourasky Medical Center, and the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. firstname.lastname@example.org
UI - 21453198
AU - Sober AJ; Chuang TY; Duvic M; Farmer ER; Grichnik JM; Halpern AC; Ho V;
TI - Holloway V; Hood AF; Johnson TM; Lowery BJ; The Guidelines/Outcomes Committee Guidelines of care for primary cutaneous melanoma.
SO - J Am Acad Dermatol 2001 Oct;45(4):579-86
UI - 21466976
AU - Konjevic G; Jovic V; Radulovic S; Jelic S; Dzodic R; Spuzic I
TI - Therapeutic implications of the kinetics of immunomodulation during single or combined treatment of melanoma patients with dacarbazine and interferon-alpha.
SO - Neoplasma 2001;48(3):175-81
AD - Institute for Oncology and Radiology of Serbia, Belgrade, Yugoslavia.
The therapy of metastatic melanoma has not given satisfactory results. Single chemo- or immunotherapeutic agents in the adjuvant setting or combined chemoimmunotherapy for metastatic disease have generally been evaluated only in terms of clinical benefit. Considering that dacarbazine (DTIC) and interferon-alpha (IFN-alpha) are among the most frequently used agents in the treatment of melanoma, the aim of this study was to evaluate the kinetics of immunological changes during adjuvant treatment of melanoma patients with DTIC or with IFN-alpha monotherapy, as well as by their combination in metastatic disease. The evaluated immunological parameters showed significant early increase in the activity of NK (natural killer) cells, CD4/CD8 ratio, CD4+ T cell number in patients treated with combined chemoimmunotherapy and an increase in expression of the early activation antigen CD38 on CD8+ cytotoxic T cells, both, in patients treated with combined chemoimmunotherapy and with IFN-alpha alone, while, no significant change in any one parameter was detected in the group of patients receiving DTIC. The kinetics of the observed immunological changes, restricted to combined chemoimmunotherapy, indicate that the engagement of antitumor immune response appears early but is short-lived and that this favorable effect should be augmented and prolonged by the timely introduction of additional immunomodulating agents.
UI - 20212767
AU - Brinckerhoff LH; Thompson LW; Slingluff CL Jr
TI - Melanoma vaccines.
SO - Curr Opin Oncol 2000 Mar;12(2):163-73
AD - University of Virginia Health System, Department of Surgery, Charlottesville 22908, USA.
Remarkable advances in tumor vaccination have been made since Coley first deliberately infected cancer patients with both live and heat-killed bacteria. Melanoma is the most immunogenic solid tumor and, as such, has served as the major model for tumor vaccine investigation in both the laboratory and the clinic. Many advances in the field of melanoma vaccination have been based on an improved understanding of the cellular interaction required to induce a specific antitumor immune response. As a result of this new knowledge, many clinical trials of melanoma vaccines are now under way, and vaccines for metastatic melanoma have shown evidence of clinical effectiveness. This paper outlines the current status of melanoma vaccination.
UI - 21341692
AU - Bystryn JC; Zeleniuch-Jacquotte A; Oratz R; Shapiro RL; Harris MN; Roses
TI - DF Double-blind trial of a polyvalent, shed-antigen, melanoma vaccine.
SO - Clin Cancer Res 2001 Jul;7(7):1882-7
AD - Ronald O. Perelman Department of Dermatology, Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, New York 10016, USA. email@example.com
A polyvalent melanoma vaccine prepared from shed antigens stimulates humoral and cellular immune responses and improves survival compared with historical controls. We conducted a double-blind, prospectively randomized, placebo-controlled trial to assess whether this vaccine could slow the progression of resected melanoma. Thirty-eight patients with resected melanoma metastatic to regional nodes (American Joint Committee on Cancer stage III) who had a particularly poor prognosis on the basis of the nodes being clinically positive or two or more histologically positive nodes were randomly assigned in a 2:1 ratio to treatment with 40 microg of melanoma or placebo (human albumin) vaccine, both of which were bound to alum as an adjuvant. Immunizations were given intradermally into the extremities every 3 weeks x 4, monthly x 3, every 3 months x 2, and then every 6 months for 5 years or until disease progression. Twenty-four patients were treated with the melanoma, and 14 patients were treated with the placebo vaccine. The groups were evenly balanced with respect to prognostic factors. Median length of observation was 2.5 years. There was no local or systemic toxicity. By Kaplan-Meier analysis, median time to disease progression was two and a half times longer in patients treated with melanoma vaccine compared with that in patients treated with placebo vaccine, i.e., 1.6 years (95% confidence interval, 1.0-3.0 years) compared with 0.6 year [95% confidence interval, 0.3-1.9 year(s)]. By Cox proportional hazards analysis, this difference was significant at P = 0.03. Overall survival was 40% longer in the melanoma vaccine-treated group (median overall survival of 3.8 years versus 2.7 years), but this difference was not statistically significant. In a double-blind and placebo-controlled trial, these results suggest that immunization with a melanoma vaccine may be able to slow the progression of melanoma. Although statistically significant, these results must be interpreted with caution because they are based on a small number of patients.
UI - 21291617
AU - Smyth J; Boneterre ME; Schellens J; Calvert H; Greim G; Wanders J;
TI - Hanauske A; EORTC Early Clinical Studies Group Activity of the dolastatin analogue, LU103793, in malignant melanoma.
SO - Ann Oncol 2001 Apr;12(4):509-11
AD - ICRF Medical Oncology Unit, Western General Hospital, Edinburgh, UK. firstname.lastname@example.org
LU103793, a synthetic analogue of dolastatin 15, showed interesting pre-clinical activity in melanoma xenografts. In this phase II multicentre trial, 80 chemotherapy-naive patients with metastatic melanoma received a total of 218 cycles of treatment. The response rate showed one complete and three partial responses of median duration six months (range 3-9.1). Toxicity was moderate, mostly haematological (neutropenia grade 4 in 16%, grade 3 in 3%). There were no significant problems with hypertension or other non-haematological toxicities.
UI - 21325280
AU - Kristjansson S; Helgason AR; Rosdahl I; Holm LE; Ullen H
TI - Readiness to change sun-protective behaviour.
SO - Eur J Cancer Prev 2001 Jun;10(3):289-96
AD - Department of Cancer Prevention, Stockholm Center of Public Health, Karolinska Hospital, Sweden. email@example.com
The incidence of malignant melanoma and non-melanoma skin cancers has increased rapidly in Sweden during the last 20 years. The best-known way to revert this trend is primary prevention. Matching health messages to readiness to change in the population may enhance the effect of community-based prevention. The aims of this study were to investigate readiness to change sun-protective behaviour in two groups (visitors to mobile screening units and beach-goers) and to test a single-item algorithm in assessing the stage of change in sun-protective behaviour. Seven hundred and forty-two visitors to the mobile screening units and 202 individuals on nearby beaches answered a short questionnaire. The assessment of readiness to change was based on stages of change in sun-protective behaviour modified from the Transtheoretical Model of Behaviour Change. As expected, the visitors to the screening units were more often in action/maintenance stages than the beach group for most sun-protective behaviours. In conclusion, the single-item algorithm method appears to be sensitive to assess readiness to change sun-protective behaviour, based on the Transtheoretical Model of Behaviour Change. This method can be incorporated into population surveys and may aid in developing successful skin cancer prevention programmes.
UI - 21367186
AU - Kropp J; Stein A; Hackert I; Sebastian G; Meurer M; Gruning T; Liepe K;
TI - Pinkert J; Franke WG Accuracy of the intra-operative radioguided localization of the sentinel lymph node (SLN) 24 hours after lymphoscintigraphy in patients with malignant melanoma.
SO - Nuklearmedizin 2001 Jun;40(3):86-90
AD - Department of Nuclear Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, Deutschland. firstname.lastname@example.org
AIM: For optimized logistics for the sentinel lymphadenectomy (SL) it might be helpful for the clinics involved if a longer time period between the lymphoscintigraphy (LS) and surgery is possible. Therefore, we investigated if a precise localization of the sentinel lymph node is possible 24 hours after LS. METHODS: 78 patients with primary malignant melanoma (MM; n = 44) or with MM pre-operated by excisional biopsy (n = 34) were investigated. In 40 cases the tumor was localized on the trunk and in 38 cases on the extremities. Mean MM thickness was 2.68 mm (range: 0.29 to 12 mm). In all patients a lymphoscintigraphy (LS) with an average of 85 MBq of Tc-99m nanocolloid was performed one day prior to surgery. Immediately after tracer application dynamic data acquisition was started at a LFOV gamma camera followed by a whole body scan. With a hand-held gamma detector (C-Trak) 2, 4, 6, 8, and 24 hours after tracer administration the SLN was identified and the counts registered. RESULTS: 94 SLNs were identified in 87 lymphatic basins from which 86 could be resected. Nine MM showed two draining channels. After 24 hours 15.5% (as an average) of the initial counts could be measured in the SLN. The uptake in the SLN in pre-operated versus patients with primary tumor was statistically not significant (p = 0.4). In 16 cases (20.5%) the SLN was tumor positive. Four of those patients developed distant metastases and two died within the first year. None of the patients with negative SLN developed distant metastases or died. CONCLUSION: The remaining activity in the SLN up to 24 hours after administration is sufficient for their intra operative localization. The method of lymphoscintigraphy and localization of the SLN by a hand-held gamma detector optimizes the intra operative identification of the SLN in patients with malignant melanoma.
UI - 21433713
AU - Dummer R; Bosch U; Panizzon R; Bloch PH; Burg G; Task Force 'Skin
TI - Cancer'. Swiss National Program against Cancer. Swiss Cancer League Swiss guidelines for the treatment and follow-up of cutaneous melanoma.
SO - Dermatology 2001;203(1):75-80
AD - Department of Dermatology, University Hospital of Zurich, Switzerland. email@example.com
Melanoma is the most common lethal cutaneous neoplasm. There is major controversy over the best management of this malignancy. In order to harmonize treatment and follow-up of melanoma patients, guidelines for the management of melanoma in Switzerland have been inaugurated. They have been approved by all Swiss medical societies involved in the care of melanoma patients. Copyright 2001 S. Karger AG, Basel
UI - 21523850
AU - Serrano A; Tanzarella S; Lionello I; Mendez R; Traversari C;
TI - Ruiz-Cabello F; Garrido F Rexpression of HLA class I antigens and restoration of antigen-specific CTL response in melanoma cells following 5-aza-2'-deoxycytidine treatment.
SO - Int J Cancer 2001 Oct 15;94(2):243-51
AD - Servicio de Analisis Clinicos, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Granada, Spain.
Cell surface expression of HLA class I/peptide complexes on tumor cells is a key step in the generation of T-cell-based immune responses. Several genetic defects underlying the lack of HLA class I expression have been characterized. Here we describe another molecular mechanism that accounts for the complete absence of HLA class I molecule expression in a tumor line (MSR3-mel) derived from a melanoma patient. Hypermethylation of the MSR3-mel DNA, specifically of HLA-A and -B genes, was identified, which resulted in loss of HLA class I heavy chain transcription. Treatment of MSR3-mel cells with the demethylating agent 5'-aza-2'-deoxycytidine (DAC) allowed HLA-A and -B transcription, restoring cell surface expression of HLA class I antigens and tumor cell recognition by MAGE-specific cytotoxic T lymphocytes. The MSR3-mel line was obtained from a metastatic lesion of a nonresponding patient undergoing MAGE-3.A1 T-cell-based peptide immunotherapy. It is tempting to speculate that the hypermethylation-induced lack of HLA class I expression is the cause of the impaired response to vaccination. This study provides the first evidence that DNA hypermethylation is used by human neoplastic cells to switch off HLA class I genes, thus providing a new route of escape from immune recognition. Copyright 2001 Wi