Phenotypic changes in melanoma metastases during systemic interferon alpha-2 therapy. II. Increase of intra-tumoral infiltration with macrophages

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Adjuvant reactivity predicts survival in patients with “high‐risk” primary malignant melanoma treated with systemic BCG

We report the prognostic importance of strength of reaction to BCG, tumor histology and clinical factors in patients with previously untreated high‐risk (Clark, III, IV and V) primary malignant melanoma. One hundred and one such patients received high‐dose BCG (1 × 108 viable units) by Heaf gun as an adjuvant to standardized primary surgery according to EORTC Protocol 18741. Univariate analysis of disease‐free interval (DFI) indicates that the degree of maximum reaction to BCG (p = 0.0003), Breslow thickness (p = 0.0003) and Clark level (p = 0.002) are highly significant prognostic factors. When a multivariate model using Cox's proportional hazard regression was used for DFI, the degree of maximum reaction to BCG and Breslow thickness were by far the most significant criteria. A prognostic equation was obtained to predict DFI from maximum BCG reaction and Breslow thickness. From analysis of the “scores” calculated in this way it appears that the two variables act independently. This technique permits the determination of values that are predictive of DFI and discriminate between subgroups of patients with different DFI characteristics (5 groups, p< 0.0001). This exercise was repeated for survival and similar results were obtained. The degree of a patient's immune reaction to BCG administered therapeutically is of paramount importance in determining the likelihood of survival. This factor and the Breslow thickness can be integrated to produce a mathematical equation which accurately predicts survival for appropriately treated melanoma patients. Copyright © 1981 Wiley‐Liss, Inc. A Wiley CompanySCOPUS: ar.jFLWNAinfo:eu-repo/semantics/publishe

N-(Phosphonacetyl)-l-aspartate (PALA) in advanced malignant melanoma: A phase II trial of the EORTC malignant melanoma cooperative group

Thirty-nine patients with measurable advanced malignant melanoma were entered in a phase II trial with PALA. Among the 36 evaluable patients there were 18 men and 18 women, with a median age of 53 yr (29-73) and a median performance status (Karnofsky) of 100 (50-100). Indicator lesion consisted essentially of soft tissue lesions (29 patients) and/or lung metastases (9 patients). Only three patients had received prior chemotherapy. PALA was given as a 60-min i.v. infusion at a daily dose of 2.5 g/m2 for two consecutive days. Courses were repeated every two weeks. A median number of 3 courses (2-8) were administered. Partial response (> 50%) was obtained in 4 patients for 6-17 weeks. Eight patients had stable disease after 3 courses of PALA and 24 had progressive disease. Toxic effects were generally mild to moderate and mainly included cutaneous toxicity, nausea and vomiting, stomatitis, and diarrhea. Myelosuppression was rare and negligible. It is concluded that PALA given at the dose schedule selected for this trial is fairly well tolerated and has borderline antitumor activity in good-risk patients with advanced malignant melanoma. © 1982.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

The eortc melanoma group exchange program: Evaluation of a multicenter monoclonal antibody study

In the framework of the European Organisation for Research and Treatment of Cancer (EORTC), the Immunology and Pathology Subgroups of the Malignant Melanoma Cooperative Group undertook a large multicenter monoclonal antibody (MAb) study. Fourteen laboratories from 7 European countries tested a panel of 23 MAbs for immunohistological staining reactivity for malignant and non‐malignant lesions involving the melanocytic lineage. A standardized im‐munoperoxidase procedure was used and the results were evaluated using a standard protocol and data evaluation form developed in collaboration with the EORTC Data Center. According to this analysis, the antibodies in the panel could be classified into 3 main groups. The first group of MAbs includes those antibodies which stained the majority (>80%) of all primary tumors, irrespective of their Breslow thickness and the majority of metastatic lesions. In addition, these MAbs stained a high percentage of cells within a given lesion. Several antibodies of Group I were likewise reactive with the majority of naevoblasts and with normal melanocytes. The second group of MAbs included antibodies reacting only with a limited number of primary melanomas and metastatic lesions. Antibodies of Group II reacted only weakly, if at all, with normal melanocytes or naevocytes. The percentage of cells within a malignant lesion stained by these MAbs was always rather tow. The MAb group III detected surface structures whose expression appeared to be related to tumor progression; they did not react or reacted only weakly with naevi, and they all reacted with a small number of early primary melanomas (<0.75 mm). The number of lesions stained increased with increasing Breslow thickness. Our study suggests that the application of a panel of well defined MAbs might be of diagnostic and prognostic value in evaluating malignant melanoma. Copyright © 1991 Wiley‐Liss, Inc. A Wiley CompanySCOPUS: ar.jFLWNAinfo:eu-repo/semantics/publishe

Tamoxifen as a single agent for advanced melanoma in postmenopausal women. A phase II study of the EORTC malignant melanoma cooperative group

Between 1983 and 1989 a phase II study was carried out by the EORTC Malignant Melanoma Cooperative Group in which postmenopausal women with advanced melanoma but a good performance status received tamoxifen, 40 mg per day, as a single agent. From 12 centres, 114 patients were registered of whom 107 appeared to be eligible and 102 evaluable. Seven died of progressive disease within 4 weeks, eight others had early progressive disease (of whom seven died within 7 weeks). The response rate was 4.9%, the complete response rate 1%. Without prior chemotherapy three of 58 responded, with prior chemotherapy two of 44. Except for one of 46 patients with lung metastases who experienced a PR of these metastases, all responders were patients with slowly growing small soft tissue metastases. We conclude that, because of the few side effects, tamoxifen can be recommended for (postmenopausal) patients who have only a small number of slowly growing metastases and who are not yet candidates for treatment with toxic drugs. © 1992 Rapid Communications of Oxford Ltd.SCOPUS: ar.jinfo:eu-repo/semantics/publishe