National Cancer Institute®
Last Modified: July 1, 2002
UI - 11880712
AU - Eggermont AM
TI - European approach to the treatment of malignant melanoma.
SO - Curr Opin Oncol 2002 Mar;14(2):205-11
AD - Department of Surgical Oncology, Erasmus University Medical Center, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands. email@example.com
The European approach to the treatment of each stage of malignant melanoma can be characterized as cautious, avoiding unwarranted mutilation or toxicity, because phase III trials have demonstrated that an aggressive approach in surgical management, adjuvant therapy, and treatment of stage IV disease has met with little success. Phase III trials have demonstrated that wide margins, elective lymph node dissections, and prophylactic isolated limb perfusions bring no survival benefit. Primary melanoma is excised with a margin of 1 cm to maximally 2 cm and primary closure as a rule. There is no standard adjuvant therapy. High-dose interferon treatment is practiced only sporadically in Europe because its high toxicity profile and an unclear long-term impact on survival are not popular. Long-term nontoxic lower-dose interferon regimens and vaccines are currently being explored. Phase III trials have shown that highly toxic polychemotherapy or biochemotherapy has not produced a survival benefit over simple treatment with dacarbazide alone. In Europe biochemotherapy is being abandoned and various less toxic or nontoxic approaches with vaccines and antiangiogenic agents are under study.
UI - 11880715
AU - Allen PJ; Coit DG
TI - The role of surgery for patients with metastatic melanoma.
SO - Curr Opin Oncol 2002 Mar;14(2):221-6
AD - Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
When deciding to perform a resection for metastatic melanoma one should first decide whether the intent of the procedure is curative or palliative. When the resection is palliative, the success of surgical treatment will depend on the presence of identifiable symptoms, the morbidity of the procedure, the course of the disease, and the ability to communicate the treatment goals among surgeon, patient, and family. When the resection is curative, survival will depend on the ability of the surgeon to select patients with a pattern of recurrence suggestive of less aggressive tumor biology. Factors generally found predictive of improved survival, and therefore reflective of tumor biology, include longer disease-free interval, fewer numbers of metastases, and the ability to obtain a complete resection. Resection of metastases in patients who recur within one-year, who present with multiple lesions, and who present with disease that cannot be completely resected, will not result in long-term survival.
UI - 12056962
AU - Tsao H; Millman P; Linette GP; Hodi FS; Sober AJ; Goldberg MA; Haluska
TI - FG Hypopigmentation associated with an adenovirus-mediated gp100/MART-1-transduced dendritic cell vaccine for metastatic melanoma.
SO - Arch Dermatol 2002 Jun;138(6):799-802
AD - Department of Dermatology, Massachusetts General Hospital, Boston, MA 02114, USA. firstname.lastname@example.org
BACKGROUND: Reports of vitiligo associated with metastases and rare cases of spontaneous regression of disease have fueled enthusiasm for immunologic approaches to the treatment of advanced melanoma. More recent strategies have focused on using antigen-presenting dendritic cells as vaccines. OBSERVATIONS: We observed 3 cases of leukoderma associated with a novel adenovirus-mediated gp100/MART-1-transduced dendritic cell (MART indicates melanoma antigen recognized by T cells). All 3 patients had advanced metastatic melanoma. Despite the development of this leukodermic response, all patients experienced disease progression while under treatment. CONCLUSION: We provide the initial evidence for effective induction of a leukodermic response with a gp100/MART-1-transduced dendritic cell vaccine.
UI - 12057119
AU - Sun W; Schuchter LM
TI - Metastatic melanoma.
SO - Curr Treat Options Oncol 2001 Jun;2(3):193-202
AD - University of Pennsylvania Cancer Center, Hematology-Oncology Division, 16 Penn Tower, 3400 Spruce Street, Philadelphia, PA 19104-4283, USA.
The overall survival for patients with metastatic melanoma ranges from 4.7 to 11 months, with a median survival of 8.5 months. Standard treatment for patients with metastatic melanoma has not been defined. The range of treatment options includes close observation, surgical resection of isolated metastases, therapy with dacarbazine, combination chemotherapy, and participation in clinical trials. Numerous chemotherapeutic agents have shown activity in the treatment of malignant melanoma. Dacarbazine (DTIC-Dome; Bayer Corporation, West Haven, CT) has a response rate of 15% to 20% and remains the reference agent for the treatment of metastatic disease. Additional agents with single-agent activity include cisplatin, (Platinol-AQ; Bristol-Myers Oncology, Princeton, NJ); carmustine (BiCNU; Bristol-Myers Oncology, Princeton, NJ); paclitaxel (Taxol; Bristol-Myers Squibb, Princeton, NJ); and docetaxel (Taxotere; Rhone-Poulenc Rorer Pharmaceuticals, Collegeville, PA). Temozolomide (Temodar; Schering-Plough, Kenilworth, NJ), which is essentially an oral form of dacarbazine but with greater central nervous system penetrance, is associated with a response rate of 20%. Combination chemotherapy with or without tamoxifen has been extensively evaluated in patients with metastatic melanoma. Although the initial results with the Dartmouth regimen (dacarbazine, cisplatin, carmustine, and tamoxifen) were associated with overall response rates of 50% to 55% in single-institution studies, results from larger multicenter studies reveal responses rates ranging from 10% to 20%. Based on the results of several clinical trials, there is no evidence that the addition of tamoxifen improves the response rate. Another combination regimen is cisplatin, vinblastine, and dacarbazine (CVD), which is associated with a 20% to 25% response rate. There has been widespread interest in developing immunotherapies against metastatic melanoma. Interferon (IFN)-alfa and interleukin (IL)-2 as single agents have produced response rates in the 15% to 20% range. Biochemotherapy, which is a combination of immunotherapy and cytotoxic chemotherapy, has been studied in patients with metastatic melanoma. Multiple phase II studies have demonstrated high response rates but unclear impact on overall survival. Therapy is associated with significant toxicity. Ongoing randomized clinical trials will clarify the role of biochemotherapy in patients with metastatic melanoma. Ongoing new approaches to treatment include the therapeutic use of vaccines alone or in combination with cytokines.
UI - 12057066
AU - Agarwala SS
TI - Intermediate- and high-risk melanoma.
SO - Curr Treat Options Oncol 2002 Jun;3(3):205-17
AD - University of Pittsburgh, N-755 MUH, 200 Lothrop Street, Pittsburgh, PA 15261, USA. email@example.com
Intermediate and high risk for recurrence melanoma comprise a unique subset of patients with surgically treatable melanoma for whom cure is possible but relapse and distant metastases likely. Strategies to improve the prognosis for such patients with effective adjuvant therapies are critical. In recent randomized trials conducted by the cooperative groups in the United States of patients at high risk for recurrence (patients with thick primary melanomas and those with regional lymph node metastases) administered adjuvant therapy with high-dose interferon alfa-2b (HDI), relapse-free survival and overall survival rates improved significantly. Research efforts in this area continue to assess the role of intermediate-dose interferon, but there is no convincing evidence of success of the lower-dose regimens, despite the reduction in toxicity. For a subset of patients at highest risk (two or more involved lymph nodes), a regimen of therapy for metastatic stage IV melanoma (interleukin-2 based biochemotherapy) is being compared with HDI in an ongoing phase III trial. For intermediate-risk melanoma, no effective adjuvant therapy is available. For such patients, enrollment in ongoing clinical trials assessing the role of shorter courses of HDI or vaccines should be encouraged.
UI - 11824887
AU - Young AM; Marsden J; Goodman A; Burton A; Dunn JA
TI - Prospective randomized comparison of dacarbazine (DTIC) versus DTIC plus interferon-alpha (IFN-alpha) in metastatic melanoma.
SO - Clin Oncol (R Coll Radiol) 2001;13(6):458-65
AD - CRC Trials Unit, Institute of Cancer Studies, The Medical School, Edgbaston, Birmingham, UK. firstname.lastname@example.org
Dacarbazine (DTIC) has been the mainstay of chemotherapy for metastatic melanoma for over two decades, but only 15%-20% of patients respond and benefit is usually transient. Randomized studies combining DTIC with interferon-alpha (IFN-alpha) in advanced disease have so far been inconclusive in terms of response and survival. We report a randomized prospective pilot Phase III trial of DTIC +IFN-alpha in patients with metastatic melanoma. The primary endpoint was death. A total of 61 in survival between groups were assessed using log-rank analysis. Quality of life was measured using the European Organization for Research on Treatment of Cancer QLQ C30 (+3) questionnaire. Fifty-seven patients died during the study. The median survival for patients receiving DTIC was 7.2 months (95% confidence interval (CI) 4.4-9.0); it was 4.8 months for DTIC + IFN-alpha (95% CI 2.0-8.0). There was no significant difference in survival between the two treatment arms (chi2 unadjusted = 0.15, P = 0.70; chi2 adjusted = 0.01, P = 0.91). The 6-month survival of those patients randomized to DTIC alone was 58% compared with 40% for those patients randomized to DTIC + IFN-alpha. There were no differences in quality of life between treatment groups. This study failed to demonstrate a survival benefit for patients receiving IFN-alpha in combination with DTIC. These results are inconclusive primarily owing to the small size of the trial. A meta-analysis is required to determine whether there is a role for the addition of IFN-alpha to DTIC in the treatment of this disease.
UI - 12076289
AU - Nguyen XD; Eichler H; Sucker A; Hofmann U; Schadendorf D; Kluter H
TI - Collection of autologous monocytes for dendritic cell vaccination therapy in metastatic melanoma patients.
SO - Transfusion 2002 Apr;42(4):428-32
AD - Institute of Transfusion Medicine and Immunology, Red Cross Blood Service of Baden-Wurttemberg, Faculty of Clinical Medicine Mannheim, Germany. email@example.com
BACKGROUND: Dendritic cells (DCs) for immunotherapy of malignant melanoma can be generated from partially enriched monocytes prepared from PBMNCs. The feasibility of a single steady-state leukapheresis procedure to enrich monocytes for a complete vaccination series with up to 10 vaccinations was investigated. STUDY DESIGN AND METHODS: Thirty-eight patients (27 males and 11 females) with metastatic melanoma were enrolled in the study. All leukapheresis procedures were performed by a continuous flow method (Spectra, Cobe BCT) with a standard MNC program. RESULTS: An average of 11.7 L (range, 8-14 L) of whole blood was processed within 197.3 +/- 23.7 minutes, and a mean of 13.5 +/- 5.7 x 109 WBCs in a final volume of 191.0 +/- 24.2 mL was collected. The MNC purity in the apheresis component was 81.5 +/- 15.1 percent, from which 29.8 +/- 14.7 percent were monocytes. Thus, 11.0 +/- 5.0 x 109 MNCs and 3.2 +/- 2.0 x 109 monocytes were collected per procedure. Linear regression analysis revealed a high correlation between the absolute number of monocytes in peripheral blood before the apheresis procedure and the number of monocytes in the collected component (r=0.74, p < 0.0001). For the generation of DCs, 1.6 +/- 0.8 x 109 MNCs were plated into culture dishes; 3.2 +/- 1.8 percent of the cultured cells matured to DCs, which resulted in 56.5 +/- 49.4 x 106 DCs (range, 6.3-178) per patient for the complete vaccination series. CONCLUSION: A target dose of monocytes for the complete vaccination series could be obtained by a single convenient, safe, steady-state leukapheresis procedure in each patient without the need for G-CSF mobilization. The absolute number of monocytes in peripheral blood before the apheresis procedure is the best predictive variable for the yield of monocytes in the apheresis component.
UI - 11986187
AU - van Ginkel RJ; Limburg PC; Piers DA; Koops HS; Hoekstra HJ
TI - Value of continuous leakage monitoring with radioactive iodine-131-labeled human serum albumin during hyperthermic isolated limb perfusion with tumor necrosis factor-alpha and melphalan.
SO - Ann Surg Oncol 2002 May;9(4):355-63
AD - Department of Surgical Oncology, Groningen University Hospital, Groningen, The Netherlands.
BACKGROUND: The aim of this study was to analyze the value of continuous leakage monitoring with radioactive iodine-131-labeled human serum albumin (RISA) in patients treated with hyperthermic isolated limb perfusion with tumor necrosis factor-alpha (TNF alpha) and melphalan. METHODS: Forty-eight patients with melanoma (n = 14) or soft tissue sarcoma (n = 34) of an extremity underwent 51 perfusions. Perfusion was performed at the iliac level in 22 cases, at the popliteal level in 16 cases, at the femoral level in 7 cases, and at the axillary level in 6 cases. Leakage rates and perfusion circuit and systemic levels of TNF alpha, interleukin-6, and C-reactive protein were determined, as were systemic hematological and metabolic profiles and tumor response. RESULTS: The mean isotopically measured leakage was 2.9%. Systemic leakage was < or = 2% in 28 perfusions and >2% in 23 perfusions. The correlation between the maximal monitored leakage and maximal systemic TNF alpha levels was.7114. The area under the curve for TNF alpha in the perfusion circuit, indicating the exposure of the perfused limb to TNF alpha, was 18.7% lower in the >2% leakage group. No significant differences in tumor response were found between groups. The area under the curve for systemic TNF alpha, indicating the exposure of the patient to TNF alpha, was 18.1 times higher in the >2% leakage group, resulting in a significant decrease in leukocyte and platelet count, hyperbilirubinemia, hypocholesterolemia, and proteinemia. No beneficial effect of the systemically leaked TNF and melphalan was seen on the occurrence of distant metastasis during follow-up. There was a significant difference between perfusions performed at the iliac and femoral levels compared with leakage values at the popliteal level. CONCLUSIONS: A good correlation between RISA leakage measurement and TNF alpha exposure during and after hyperthermic isolated limb perfusion with TNF alpha and melphalan was demonstrated. RISA leakage measurement serves as a good guide for the effectiveness of isolation during perfusion. If leakage exceeds the 2% limit during perfusion, less exposure of the tumor-bearing limb to TNF alpha, increased exposure of the patient systemic circulation to TNF alpha, and more systemic side effects can be expected.
UI - 12094542
AU - Kuriakose P; Gandara DR; Perez EA
TI - Phase I trial of edatrexate in advanced breast and other cancers.
SO - Cancer Invest 2002;20(4):473-9
AD - Division of Hematology/Oncology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
Edatrexate (EDX) (10-ethyl-10-deazaaminopterin or 10-EDAM) is an analogue of methotrexate with improved pre-clinical antitumor activity, more selective cellular uptake, and with more extensive formation of intracellular polyglutamate metabolites. A phase I trial in advanced cancer using EDX was initiated to determine the toxicities associated with the use of a biweekly schedule of intravenous EDX, and to carry out a dose escalation to define the maximum tolerated dose employing this schedule. Thirty-four patients were enrolled in this phase I trial. Thirty-three patients were treated in cohorts of at least three patients (except at one dose level, 210 mg m-2, where there were only two patients). Dose escalations of EDX were administered starting with 100 mg m-2, and progressing through 120, 140, 160, 180, 210, 240, and 270 mg m-2. Edatrexate was administered by intravenous infusion over 20 min, and cryotherapy using ice chips was given prophylactically for 5 min before, during, and 15 min after each EDX treatment. The dose-limiting toxicity could not be reached in this study because it had to be closed on account of competing protocols using EDX in combination regimens. Of note though, was that the delivered dose intensity at the 160 mg m-2 week-1, was higher than the previously used or recommended phase II doses. Anemia was mild and white blood corpuscle toxicity was mostly of grade 1 or 2. One patient had grade 4 neutropenia and one had grade 3 thrombocytopenia. Of the non-hematological toxicities, nausea, vomiting, and diarrhea were mild and tolerable. Mucositis, which was the dose-limiting toxicity in previous studies, was seen in 30% of the patients, but was predominantly a grade 1 toxicity. This could have been due to either the different schedule of EDX used in this study or the use of cryotherapy. Substantial antitumor effects were noted, with two near-complete complete responses at the 120 and 160 mg m-2 levels. Additionally, six partial responses and one minor response were observed, and stable disease was observed in seven patients. Despite achieving antitumor activity at different dose levels, a clear-cut dose response was not evident at the levels tested. We feel that the biweekly EDX schedule is a tolerable regimen, which allows a higher dose intensity than weekly administration, and that EDX is an active agent for the treatment of patients with metastatic cancer.
UI - 12101571
AU - Demidov LV; Martynova EV
TI - [Retrospective evaluation of the safe reduction of surgical margins of resected stage-IIA cutaneous melanoma of the trunk and extremities]
SO - Vopr Onkol 2002;48(1):68-73
AD - N.N. Blokhin Center for Oncology Research, Russian Academy of Medical Sciences, Moscow.
The paper deals with analysis of 102 case histories locally-advanced 1.51-4.00 mm-thick cutaneous melanomas (CM) of the trunk and arms and legs operated on at the Center's Clinics and 52--at the Regional Oncological Dispensary, Samara. The effectiveness of relatively conservative procedures of treating CM of "medium" thickness and "intermediate" prognosis were assessed by histological analysis of resected material. CMs with such characteristics conform to the specifications of stage IIA of the criteria used by the American Joint Committee on Staging of Cancer (AJCC). The study of the time and frequency of relapse and dissemination of tumor in 154 patients provided the guide-lines for determining optimal extent of surgery to excise CM stage IIA of the trunk and arms and legs. Excision of 1.5-4.00 mm-thick CMs with 2 cm-wide margins left should be considered safe and less traumatic.
UI - 12094637
AU - Wysocki PJ; Karczewska A; Mackiewicz A
TI - [Gene modified tumor vaccines in therapy of malignant melanoma]
SO - Otolaryngol Pol 2002;56(2):147-53
AD - Zaklad Immunologii Nowotworow Katedry Onkologii AM im. K. Marcinkowskiego, Wielkopolskie Centrum Onkologii w Poznaniu.
Over the years the incidence of malignant melanoma in Poland as well as in other countries has been continuously increasing. Surgery is a treatment of choice in the early stages of primary lesions. Advanced malignant melanoma however is resistant to chemotherapy or radiotherapy. Therefore there is a need for new, more effective treatments. In the last years biotherapy such as immunotherapy is focusing a lot of attention. Unfortunately, systemic administration of immunostimulatory factors is very often associated with severe side effects. Thus, concepts of specific immunotherapies such as immunogene therapy have been developed. Currently, various gene therapy strategies of malignant melanoma are being evaluated in multiple clinical trials carried out all over the world. They include gene modified cancer vaccines (GMTV) modified with genes encoding (i) cytokines or (ii) costimulatory molecules and dendritic cells modified with (iii) genes encoding tumor Department of Cancer Immunology USOMS, at GreatPoland Cancer Center in Poznan, Poland a GMTV has been tested in malignant melanoma patients. For the last 6 years more than 220 patients were enrolled into study of GMTV consisting of melanoma cells modified with genes encoding IL-6 and its agonistic soluble receptor (sIL-6R). More than 25% of objective clinical responses and significant life extension were observed. The encouraging results formed a basis for design of a phase III prospective, randomized clinical study.
UI - 11831644
AU - Grossman D; Altieri DC
TI - Drug resistance in melanoma: mechanisms, apoptosis, and new potential therapeutic targets.
SO - Cancer Metastasis Rev 2001;20(1-2):3-11
AD - Department of Dermatology and the Huntsman Cancer Institute, University of Utah, Salt Lake City, USA.
Melanoma is the most aggressive form of skin cancer. Patients with advanced disease, such as lymph node involvement and distant metastases, have 5-year survival rates of 50% and 10-20%, respectively. This poor prognosis largely results from resistance to conventional chemotherapy, namely cytotoxic drugs. The basis for drug resistance in melanoma is most likely dysregulation of apoptosis, although other mechanisms including drug transport, detoxification, and enhanced DNA repair may also play a role. Defects at multiple levels and in both major apoptotic pathways have been described in melanoma. Our laboratory has identified an inhibitor of apoptosis, termed survivin, that is expressed in melanoma and required for maintenance of melanoma cell viability. Targeting of survivin and other apoptotic regulators increases the sensitivity of melanoma cells to cytotoxic drugs, and may provide a promising new therapeutic approach to cancer.
UI - 12052761
AU - Hsueh EC; Essner R; Foshag LJ; Ye W; Morton DL
TI - Active immunotherapy by reinduction with a polyvalent allogeneic cell vaccine correlates with improved survival in recurrent metastatic melanoma.
SO - Ann Surg Oncol 2002 Jun;9(5):486-92
AD - John Wayne Cancer Institute, 2200 Santa Monica Boulevard, Santa Monica, CA 90404, USA. firstname.lastname@example.org
BACKGROUND: We have observed prolonged survival in patients undergoing vaccine reinduction after resection of recurrent metastatic melanoma and adjuvant polyvalent allogenic cell vaccine (PACV) immunotherapy. We hypothesized that reinduction with a more intensive vaccine regimen would re-stimulate specific immune responses that were correlated with survival after recurrence. METHODS: From 1996 to 1998, 194 patients developed recurrence during adjuvant PACV (CancerVax vaccine) treatment after resection of metastatic melanoma. Recurrent disease was treated with or without vaccine reinduction. Reinduction regimen entailed an increased vaccine frequency and coadministration of two doses of bacille Calmette-Guerin (BCG). PACV Delayed-type hypersensitivity (DTH) responses were prospectively recorded. Survival was defined as the interval from recurrence to death. RESULTS: Ninety-four patients underwent reinduction immunotherapy. DTH responses to PACV before recurrence increased significantly after reinduction therapy (P =.0001). The median survival time was 37 months for reinduced patients and 17 months for other patients. On multivariate analysis, reinduction status remained a significant prognostic variable (P =.0277). In the reinduction group, there was a significant correlation between PACV DTH responses and survival (P =.0178). CONCLUSIONS: Reinduction vaccine regimen can enhance immune responses in previously immunized patients and is associated with prolonged survival after recurrence in patients receiving the same active specific immunotherapy.
UI - 12115326
AU - Eton O; Rosenblum MG; Legha SS; Zhang W; Jo East M; Bedikian A;
TI - Papadopoulos N; Buzaid A; Benjamin RS Phase I trial of subcutaneous recombinant human interleukin-2 in patients with metastatic melanoma.
SO - Cancer 2002 Jul 1;95(1):127-34
AD - Department of Melanoma/Sarcoma, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. email@example.com
BACKGROUND: Interleukin-2 (IL-2) has activity in metastatic melanoma when given in high doses by the intravenous (IV) route, but its side effects and effectiveness when given in intermediate to high doses by the subcutaneous (SC) route have not been studied adequately. This study sought to determine the maximum tolerated dose (MTD) of IL-2 administered once daily by the SC route. METHODS: Outpatients with progressive metastatic melanoma after chemotherapy were enrolled in a Phase I trial of IL-2 administered SC daily for 5 days per week for 4 consecutive weeks, repeated at 6-week intervals. Patients were instructed to drink at least 2 L of fluid daily. IL-2 pharmacokinetic studies were performed at the two highest dose levels. Toxicity was recorded weekly using the National Cancer Institute Common Toxicity Criteria. Response was assessed at 6-week intervals. RESULTS: Three patients, 6 patients, 6 patients, and 4 patients received a median of 2 courses of SC IL-2 at dose levels of 6 MIU/m(2), 9 MIU/m(2), 12 MIU/m(2), and 15 MIU/m(2), respectively. Failure to maintain adequate fluid intake was responsible for 2 episodes of syncope at the 9 MIU/m(2) dose level and for 2 incidents of reversible prerenal azotemia at the 15 MIU/m(2) dose level. IL-2 treatment was resumed in these patients without incident. At the 15 MIU/m(2) dose level, 2 patients had severe headaches, depression, and visual hallucinations requiring discontinuation of treatment. Cough and fluid retention at the end of the third and fourth weeks at the 15 MIU/m(2) dose level approximated the symptoms reported by inpatients treated by continuous IV infusion at 9 MIU/m(2) on the same schedule. There was a partial response and a complete response in subcutaneous disease at the 12 MIU/m(2) and 15 MIU/m(2) dose levels, respectively, each lasting < 2 months. Plasma IL-2 levels after SC injection of 1000-5000 pg/mL reached maximum by 3 hours and were detectable for up to 48 hours after administration. The half-lives for SC IL-2 absorbance and clearance were 1.6 hours and 5.2 hours, respectively, and the calculated area under the curve was 30,584 pg/mL x hour. CONCLUSIONS: SC IL-2 was well tolerated and had high sustained bioavailability at the higher doses studied. The MTD for a daily SC regimen was 12 MIU/m(2) and is recommended for future studies. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10631
UI - 11694871
AU - Cebrian Carretero JL; Chamorro Pons M; Montesdeoca N
TI - Melanoma of the oral cavity. Review of the literature.
SO - Med Oral 2001 Nov-Dec;6(5):371-5
AD - Servicio de Cirugia Oral y Maxilofacial, Hospital Universitario La Paz, Madrid, Spain.
Melanoma is a very aggressive tumour derived from malignant transformation of melanic cells of the basal layer of cutaneous and mucosal epithelia. Primary melanoma of the oral cavity is the most malignant tumour among head and neck tumours. Inside the oral cavity, 80% are located in the maxilla, preferentially in the palatal mucosa. Although its etiology is unknown, occasionally it forms over a preexisting melanosis of prolonged evolution. In the vast majority of cases it is asymptomatic during years and it is usually detected as a pigmented mass which is sometimes painful. Doctors who treat problems of the oral cavity must be aware of the necessity for early diagnosis of melanoma, performing biopsies of any pigmented lesion. Once it becomes clinically evident, its tendency is to grow toward adjacent structures and to form metastases in cervical lymphatic nodes, turning the tumour into a systemic disease. Prognosis of melanoma in the oral cavity is very poor. The only curative treatment is ablative surgery. Other therapeutic modalities such as: radiotherapy, chemotherapy or immunotherapy have supposed little contribution to improve survival.
UI - 12113108
AU - Sondak VK
TI - Use of adjuvant therapy in cutaneous melanoma.
SO - Expert Rev Anticancer Ther 2001 Oct;1(3):421-6
AD - Room 3306 Cancer Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0932, USA. firstname.lastname@example.org
Surgery remains the principal treatment for local, regional and isolated metastatic melanoma. Adjuvant therapy is now available for patients with high risk of recurrence after surgical treatment but is controversial and inconsistently used around the world. In 1995, high-dose interferon-alpha 2b was approved by the FDA, providing clinicians with the first adjuvant therapy for use outside a clinical trial. In this review, we discuss surgical approaches to the management of the primary lesion and regional lymph nodes and the use of high-dose interferon. We will also provide guidelines for the use of interferon and discuss current clinical trials evaluating alternate forms of adjuvant therapy.
UI - 12113109
AU - Jonasch E
TI - Melanoma vaccination: state-of-the-art and experimental approaches.
SO - Expert Rev Anticancer Ther 2001 Oct;1(3):427-40
AD - Massachusetts General Hospital, 55 Fruit Street, Cox 640, Boston, MA 02114, USA.
Vaccination therapy for human malignancies is an ever-evolving technology. Great strides are being made in our understanding of the various components of the immune system and how best to manipulate these components.
UI - 11596037
AU - Joukhadar C; Klein N; Mader RM; Schrolnberger C; Rizovski B; Heere-Ress
TI - E; Pehamberger H; Strauchmann N; Jansen B; Muller M Penetration of dacarbazine and its active metabolite 5-aminoimidazole-4-carboxamide into cutaneous metastases of human malignant melanoma.
SO - Cancer 2001 Oct 15;92(8):2190-6
AD - Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, University of Vienna Medical School, Vienna, Austria.
BACKGROUND: Dacarbazine has been on the market for approximately 3 decades but remains the most effective single agent available for the therapy of metastatic malignant melanoma (MMM). Most MMMs, however, respond poorly to dacarbazine therapy. Apart from tumor resistance at a molecular level, several studies support the notion that therapeutic failure in tumor therapy also might be attributed to an impaired transcapillary drug transfer. METHODS: On the basis of this hypothesis, the authors measured intratumor transcapillary transfer rates of dacarbazine and its active metabolite 5-aminoimidazole-4-carboxamide (AIC) by in vivo microdialysis after intravenous administration of dacarbazine at doses of 200 mg/m(2) to 1000 mg/m(2) (n = 7) in patients suffering from MMM. RESULTS: For all doses, area under the concentration curve (AUC) values for dacarbazine and AIC were not significantly different between plasma and tumor interstitium with AUC(tumor)/AUC(plasma) ratios of 0.97 +/- 0.08 (mean +/- standard error of the mean) for dacarbazine and 0.76 +/- 0.22 for AIC. AUC(0-240) values for dacarbazine and AIC measured in plasma correlated closely with corresponding AUC(0-240)values measured in the interstitium of MMMs with values of r(s) = 0.82 (P = 0.042) and r(s) = 0.90 (P = 0.037), respectively. CONCLUSIONS: The results of this study indicate favorable tumor penetration characteristics of dacarbazine and its active metabolite AIC. The relative lack of response to antineoplastic therapy with dacarbazine, thus might be explained by resistance of melanoma cells at a molecular level rather than by an inability of dacarbazine and AIC to penetrate into the interstitium of MMM. Copyright 2001 American Cancer Society.
UI - 12025019
AU - Buchanan P
TI - The role of sunscreen preparations in preventing skin cancer.
SO - Prof Nurse 2002 May;17(9):558-60
AD - Department of Dermatology, Salisbury District Hospital, Wiltshire.
Despite health campaigns and much publicity in the media on the dangers of overexposure to the sun, the incidence of skin cancer is rising. Community nurses have a vital role in educating patients about the need to use an appropriate sunscreen for their skin type and combining this with the use of protective clothing and taking measures to avoid overexposure.
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