NCI CANCERLIT^® Search: Therapy of Melanoma - September 2001

Last Modified: November 1, 2001

Skin cancer prevention.
The European Society of Skin Cancer Prevention--EUROSKIN: towards the promotion and harmonization of skin cancer prevention in Europe. Recommendations.
Interferon gamma induction in human melanoma cell/allogeneic leukocyte co-cultures is enhanced by interleukin 18 but drug resistant melanoma cells are poorer inducers of IFN-gamma.
Immune and clinical responses in patients with metastatic melanoma to CD34(+) progenitor-derived dendritic cell vaccine.
Perilesional injection of r-GM-CSF in patients with cutaneous melanoma metastases.
Surgical therapy of metastatic melanoma.
High collagenase-1 expression correlates with a favourable chemoimmunotherapy response in human metastatic melanoma.
Phase II evaluation of bryostatin-1 in metastatic melanoma.
Are responses to therapy of metastasized malignant melanoma reflected by decreasing serum values of S100beta or melanoma inhibitory activity (MIA)?
A phase II study of high dose tamoxifen and weekly cisplatin in patients with metastatic melanoma.
Prognostic factors in therapeutic lymphadenectomy in melanoma.
Treatment of head and neck melanoma, lentigo maligna subtype: a practical surgical technique.
My life has been full of narrow escapes. John McCain and his wife, Cindy, on the senator's battle with melanoma.
Melanoma of the clavicular region: multimodal treatment.

CancerMail from the National Cancer Institute

1
UI - 21227878
AU - Greinert R
TI - Skin cancer prevention.
SO - Eur J Cancer Prev 2001 Apr;10(2):123-4

2
UI - 21227884
AU - Greinert R; McKinlay A; Breitbart EW
TI - The European Society of Skin Cancer Prevention--EUROSKIN: towards the promotion and harmonization of skin cancer prevention in Europe. Recommendations.
SO - Eur J Cancer Prev 2001 Apr;10(2):157-62
AD - European Society of Skin Cancer Prevention--EUROSKIN, Dermatologisches Zentrum, Buxtehude, Germany.

3
UI - 21258440
AU - Micallef MJ; Darmanin S; Buhagiar JA; Camilleri-Podesta MT; Yamauchi H; Kurimoto M; Inglott AS; Ellul-Micallef R
TI - Interferon gamma induction in human melanoma cell/allogeneic leukocyte co-cultures is enhanced by interleukin 18 but drug resistant melanoma cells are poorer inducers of IFN-gamma.
SO - Int Immunopharmacol 2001 Feb;1(2):295-305
AD - Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine and Surgery, University of Malta, Msida. fujisaki@hayashibara.co.jp
Human melanoma Colo 679 cells were made resistant to doxorubicin (adriamycin, ADM) by continuous exposure to ascending concentrations of the drug and Colo/ADM80; a variant which grew continuously in the presence of 80 ng/ml of ADM was thus established. Human peripheral blood mononuclear cells (PBMC) produced interferon gamma (IFN-gamma) when cultured with mitomycin C (MMC)-treated parental Colo 679 cells. The synthesis of IFN-gamma was synergistically enhanced by adding interleukin-18 (IL-18) and this was IL-12-dependent because a neutralizing antibody against IL-12 almost completely inhibited IFN-gamma production while control antibodies (Abs) were inactive. The cellular sources of IFN-gamma were found to be B cells, CD8+ T cells and CD4+ T cells as revealed by flow cytometry after double staining for surface antigens and staining for intracellular IFN-gamma. Interestingly, the resistant cell line induced much less IFN-gamma production than the parental cell line under the same co-culture conditions; however, IL-18 could still enhance the production of IFN-gamma. In conclusion, our study shows that acquired resistance to anti-cancer agents can also reduce immune responses to cancer cells. However, the immunostimulatory cytokine IL-18 could still enhance IFN-gamma production in drug resistant tumor cell-PBMC cultures indicating that such immunostimulatory agents could still be beneficial in immunotherapy for patients with recurrent drug resistant tumors.

4
UI - 21413551
AU - Banchereau J; Palucka AK; Dhodapkar M; Burkeholder S; Taquet N; Rolland A; Taquet S; Coquery S; Wittkowski KM; Bhardwaj N; Pineiro L; Steinman R; Fay J
TI - Immune and clinical responses in patients with metastatic melanoma to CD34(+) progenitor-derived dendritic cell vaccine.
SO - Cancer Res 2001 Sep 1;61(17):6451-8
AD - Baylor Institute for Immunology Research, Dallas, Texas 75204, USA. j.banchereau@baylordallas.edu
Immunization to multiple defined tumor antigens for specific immune therapy of human cancer has thus far proven difficult. Eighteen HLA A*0201(+) patients with metastatic melanoma received injections s.c. of CD34(+)progenitor-derived autologous dendritic cells (DCs), which included Langerhans cells. DCs were pulsed with peptides derived from four melanoma antigens [(MelAgs) MelanA/MART-1, tyrosinase, MAGE-3, and gp100], as well as influenza matrix peptide (Flu-MP) and keyhole limpet hemocyanin (KLH) as control antigens. Overall immunological effects were assessed by comparing response profiles using marginal likelihood scores. DC injections were well tolerated except for progressive vitiligo in two patients. DCs induced an immune response to control antigens (KLH, Flu-MP) in 16 of 18 patients. An enhanced immune response to one or more MelAgs was seen in these same 16 patients, including 10 patients who responded to >2 MelAgs. The two patients failing to respond to both control and tumor antigens experienced rapid tumor progression. Of 17 patients with evaluable disease, 6 of 7 patients with immunity to two or less MelAgs had progressive disease 10 weeks after study entry, in contrast to tumor progression in only 1 of 10 patients with immunity to >2 MelAgs. Regression of >1 tumor metastases were observed in seven of these patients. The overall immunity to MelAgs after DC vaccination is associated with clinical outcome (P = 0.015).

5
UI - 21403092
AU - Hoeller C; Jansen B; Heere-Ress E; Pustelnik T; Mossbacher U; Schlagbauer-Wadl H; Wolff K; Pehamberger H
TI - Perilesional injection of r-GM-CSF in patients with cutaneous melanoma metastases.
SO - J Invest Dermatol 2001 Aug;117(2):371-4
AD - Department of Dermatology, Division of General Dermatology, University of Vienna, Vienna, Austria.
Based on evidence that granulocyte-macrophage colony stimulating factor (GM-CSF) induces a potent systemic antitumor immunity, we tested recombinant GM-CSF in advanced melanoma. Seven patients with histologically confirmed cutaneous melanoma metastases were treated with perilesional intracutaneous injections of recombinant GM-CSF and observed for a follow-up time of 5 y. All but two patients had a decrease in the total number of metastases. At the end of the 5 y follow-up three of the seven patients are still alive with only one patient receiving other than surgical therapy, and one patient died tumor free at the age of 93. The remaining three patients died from progressive melanoma. Perilesional intradermal GM-CSF therapy resulted in a mean survival time of 33 mo. The treatment was well tolerated and no side-effects other than local erythema at the injection sites and mild drowsiness were seen. Immunohistochemical analysis with staining for CD14 and GM-CSF receptor demonstrated an increased infiltration of monocytes into both injected and noninjected cutaneous melanoma metastases compared with lesions excised prior to the initiation of therapy. The same was true for CD4- and CD8-positive lymphocytes. This phenomenon, together with GM-CSF-induced leukocyte counts of more than 20,000 during therapy, support the possible impact of a systemic over a locally induced reaction by GM-CSF. To our knowledge this is the first report that intracutaneously injected GM-CSF results in long-lasting reduction of melanoma metastases.

6
UI - 20487064
AU - Spratt JS
TI - Surgical therapy of metastatic melanoma.
SO - Ann Surg Oncol 2000 Oct;7(9):713

7
UI - 21230653
AU - Nikkola J; Vihinen P; Vlaykova T; Hahka-Kemppinen M; Kahari VM; Pyrhonen S
TI - High collagenase-1 expression correlates with a favourable chemoimmunotherapy response in human metastatic melanoma.
SO - Melanoma Res 2001 Apr;11(2):157-66
AD - Department of Oncology/Radiotherapy, Turku University Central Hospital, Finland.
Matrix metalloproteinases (MMPs) are proteolytic enzymes that can degrade extracellular matrix and thus enhance metastasis. We have studied the expression of two collagenolytic MMPs in 37 samples obtained from 26 patients treated for metastatic melanoma. Interestingly, the samples showed a different expression pattern of collagenase-1 (MMP-1) and collagenase-3 (MMP-13). The samples with high expression levels of MMP-1 (n = 18) were more frequently MMP-13 negative (14 out of 18), whereas those with low expression levels of MMP-1 (n = 15) were predominantly positive for MMP-13 (nine out of 15) (P = 0.027). High expression levels of MMP-1 were associated with a favourable response to chemoimmunotherapy. Responders (n = 13) frequently had intensively MMP-1-expressing metastases (nine out of 13), especially those who achieved a complete response (five out of six). Response failures (n = 7) mainly had metastases with a low intensity of MMP-1 expression (six out of seven) (P = 0.019). There was a tendency towards longer survival among patients with intensively MMP-1-expressing tumours (median 14.3 versus 6.7 months, P = 0.068). The high expression levels of MMP-1 correlated with low MIB-1 (to nuclear antigen Ki-67) (P = 0.019) and positivity for MMP-13 was associated with high MIB-1 expression (P = 0.00048), suggesting that their different expression patterns may affect tumour growth and contribute to differences in patient survival.

8
UI - 21230656
AU - Bedikian AY; Plager C; Stewart JR; O'Brian CA; Herdman SK; Ross M; Papadopoulos N; Eton O; Ellerhorst J; Smith T
TI - Phase II evaluation of bryostatin-1 in metastatic melanoma.
SO - Melanoma Res 2001 Apr;11(2):183-8
AD - Department of Melanoma/Sarcoma Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
In this phase II study we assessed the efficacy of bryostatin-1 (NSC 339555) in metastatic melanoma patients when given intravenously either once a week at a dose of 25 microg/m2 per day over 24 h for 3 weeks or at 40 microg/m2 per day over 72 h every 2 weeks. Treatment courses were repeated every 4 weeks. Patients who had received one prior chemotherapy regimen for advanced melanoma, with or without biotherapy, were randomized to one or the other bryostatin-1 dose schedules until 12 patients were registered to each arm. Because there was one confirmed response among the 12 patients who received the 72 h dose schedule, 25 more patients were added to that arm. No prophylactic medications were given. Objective tumour measurements were used to assess the efficacy of the regimen. The National Cancer Institutes common toxicity criteria were used to grade reactions. In total, 49 patients with metastatic melanoma, none having symptomatic brain metastasis, were studied. Of these, 12 patients received the 24 h bryostatin-1 regimen, while the remaining 37 received the 72 h regimen. One patient receiving the 72 h regimen had a partial response lasting over 7 months. Muscle pain occurred in over 90% of the patients and was the dose-limiting side effect of the 72 h regimen. Grade 3/4 nausea and vomiting were more common on the 24 h regimen than on the 72 h one (35% versus 5% of patients). There was no therapy-related thrombocytopenia. Neutropenia was mild and mainly limited to patients receiving the 72 h regimen. Bryostatin-1 has limited activity against melanoma when given by 72 h intravenous infusion.

9
UI - 21361593
AU - Deichmann M; Benner A; Kuner N; Wacker J; Waldmann V; Naher H
TI - Are responses to therapy of metastasized malignant melanoma reflected by decreasing serum values of S100beta or melanoma inhibitory activity (MIA)?
SO - Melanoma Res 2001 Jun;11(3):291-6
AD - Department of Dermatology, University of Heidelberg, Vossstrasse 2, 69115 Heidelberg, Germany. martin_deichmann@med.uni-heidelberg.de
In metastatic melanoma S100beta as well as melanoma inhibitory activity (MIA) are elevated in the serum in the majority of patients. Elevation has been found to correlate with shorter survival, and changes in these parameters in the serum during therapy were recently reported to predict therapeutic outcome in advanced disease. However, the value of these markers with respect to other possible markers by multivariate analysis has not yet been proven for individual patients. In this prospective study, S100beta and MIA were measured in the serum of 67 consecutive patients before and following treatment. Analysing both the sensitivity and the specificity of the serum parameters by the areas under the receiver operating characteristics (ROC) curves, decreases in S100beta and MIA during therapy were associated with response to therapy, while increases indicated progressive disease. Unexpectedly, the individual diagnostic value of changes in tumour markers during therapy was not superior to one-point measurements at restaging. Moreover, S100beta and MIA were not superior to the conventional parameters lactate dehydrogenase and C-reactive protein (CRP) on multiple logistic regression analysis. Applying classification and regression trees (CARTs), one-point measurements of CRP was shown to be the most relevant overall parameter.

10
UI - 21361596
AU - McClay EF; McClay MT; Monroe L; Jones JA; Winski PJ
TI - A phase II study of high dose tamoxifen and weekly cisplatin in patients with metastatic melanoma.
SO - Melanoma Res 2001 Jun;11(3):309-13
AD - Department of Medicine, Division of Hematology/Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.
We have previously demonstrated that the combination of tamoxifen and cisplatin has activity in patients with metastatic melanoma. In vitro studies have demonstrated that tamoxifen and cisplatin exhibit cytotoxic synergy in human melanoma cells and that this interaction is dependent on a tamoxifen effect. The mechanism of this effect is currently under investigation in in vitro studies. In an attempt to improve the complete response rate of this regimen, we initiated a phase II trial to determine the effect of the use of high dose tamoxifen and weekly cisplatin on the complete response rate, disease-free survival and overall survival. Tamoxifen was started on day 1 initially at a dose of 240 mg/day and continued until the patient was taken off treatment. This dose was subsequently lowered to 200 mg/day. Cisplatin (80 mg/m2) was begun on day 2 and repeated weekly for a total of 3 weeks. During week 4, the patient was not treated with cisplatin but was evaluated for response. If disease stabilization or regression was documented, the patient received a second 3 week cycle of cisplatin and was then re-evaluated for response. Patients with progressive disease at any evaluation were removed from the study. In 28 consecutive patients, the overall response rate was 32% (95% confidence interval 15.88-52.35%). One patient achieved a complete remission that lasted 22 months. All other responses were partial in nature. Toxicity was primarily nausea and vomiting. Two patients developed grade 2 renal toxicity. There were no episodes of deep venous thrombosis. This phase II study demonstrates that this combination has modest activity in patients with metastatic melanoma. However, this study failed to confirm our hypothesis that high dose tamoxifen would increase the complete response rate of this combination. While this combination has activity, the overall response rate is not significantly better that that observed with the original Dartmouth regimen and the toxicity is substantial. We do not recommend this dose and schedule for routine clinical use.

11
UI - 21361597
AU - Retsas S
TI - Prognostic factors in therapeutic lymphadenectomy in melanoma.
SO - Melanoma Res 2001 Jun;11(3):315-8

12
UI - 21389014
AU - Anderson KW; Baker SR; Lowe L; Su L; Johnson TM
TI - Treatment of head and neck melanoma, lentigo maligna subtype: a practical surgical technique.
SO - Arch Facial Plast Surg 2001 Jul-Sep;3(3):202-6
AD - Department of Dermatology, University of Michigan, 1910 Taubman Center, Ann Arbor, MI 48109-0314, USA.
Melanoma with the lentigo maligna histological pattern often provides a significant and difficult challenge to the head and neck surgeon. The lentigo maligna subtype is the most common type of melanoma on the head and neck. This potentially lethal form of cancer is associated with greater nonvisual lesional extension that is often not clinically apparent. Failure to excise the entire lesion results in a higher risk of local recurrence and a poorer prognosis. The staged excision technique described herein results in histological interpretation of 100% of the peripheral margins using formalin-fixed vertical sections. Definitive local excision and soft tissue reconstruction are performed in a subsequent stage, with an assurance that 100% of the peripheral margins have been evaluated and interpreted as free of disease.

13
UI - 21413026
AU - McCain J; McCain C
TI - My life has been full of narrow escapes. John McCain and his wife, Cindy, on the senator's battle with melanoma.
SO - Newsweek 2001 Aug 20;138(8):40-1

14
UI - 21421068
AU - Lam L; Krementz E; McGinness C; Godfrey R
TI - Melanoma of the clavicular region: multimodal treatment.
SO - Arch Surg 2001 Sep;136(9):1054-8
AD - Department of Surgery, Kaiser Permanente Medical Center, 280 W MacArthur Blvd, Oakland, CA 94611-5693, USA.
HYPOTHESIS: Treatment for melanoma that has metastasized to the supraclavicular nodes should be intensive and use a multimodality approach. DESIGN: Retrospective analysis of clinical records. SETTING: Six primary care centers, 2 of which were referral centers. PATIENTS: Eighteen patients diagnosed as having a rare pattern of advanced melanoma metastatic to the clavicular region. INTERVENTION: Combined radiotherapy, chemotherapy, and thorough surgical excision of the affected nodal basins. MAIN OUTCOME MEASURE: Length of survival from time of diagnosis and treatment to time of follow-up. RESULTS: Median survival among the 18 patients was 28 months with a 22% survival rate at 5 years after diagnosis. Among patients who received radiotherapy to the clavicular node basin, mean length of survival was 88.7 months with a 50% 5-year survival rate compared with a mean length of survival of 33.8 months and an 8.3% 5-year survival rate in patients who did not receive radiotherapy (P<.001). Mean survival among patients who had supraclavicular node dissection was 45.8 months with a 23.1% survival rate at 5 years after diagnosis, compared with a mean survival of 52 months and a 20% 5-year survival rate among patients who did not receive therapeutic lymphadenectomy. Of the 11 patients who had therapeutic lymphadenectomy, 2 also received radiotherapy to the supraclavicular nodal basin and continued to be disease-free at 82 and 130 months. All long-term survivors had been treated with intra-arterial chemotherapy. CONCLUSION: In a series of patients with malignant melanoma metastatic to the clavicular lymph nodes, multimodality treatment using radiotherapy, chemotherapy, and thorough surgical excision of affected nodal basins provided an appreciable 5-year survival rate.