Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Melphalan and analogous aniline mustard derivatives were tested on antitumor activity in vitro. All compounds showed similar antiproliferative effects against melanoma B16, sarcoma 180 and leukemia P388D1. Thus, the singular clinical efficiency of melphalan may not simply be explained by a selective uptake employing amino acid carrier systems of tumor cells.
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PMID:[In vitro studies of the antitumor effect of melphalan and analogous aniline mustard derivatives]. 261 May 85

The murine plasmacytoma, MOPC-315, has been used as a tumor model to investigate the immunopotentiating effect of a low dose of cyclophosphamide (CY) or melphalan (L-PAM). Each drug was shown to shift the balance in mice bearing a late-stage tumor from a state of immunosuppression to that of potent T-cell-dependent antitumor immunity against tumor-associated antigens. The resultant immunity eradicated the extensive tumor burden not already eradicated by the direct tumoricidal activity of the drug and brought about the cure of the mice. The immunity responsible for tumor eradication, as well as the immunity responsible for the resistance of the cured mice to further tumor challenge, was mediated by the Lyt 2 subset of T-cells which contains cytotoxic T-cells. The principle of using a low dose of drug to selectively decrease suppressor cell activity so as to allow the development of antitumor immunity with the aid of autologous tumor vaccine or interleukin-2 has been exploited successfully by clinicians in therapeutic protocols for human melanoma.
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PMID:Cyclophosphamide and melphalan as immunopotentiating agents in cancer therapy. 265 52

Isolated limb perfusion (ILP) for melanoma of the extremity was first used clinically more than 30 years ago. Although ILP with chemotherapeutic agents has become routine practice in many oncologic centers, few studies have evaluated the therapeutic efficacy of particular agents. Two consecutive groups of 100 patients with stage I extremity melanoma of 1.5 mm thickness or greater were treated by ILP with either melphalan (L-PAM) or dacarbazine (DTIC). Demographics, clinical and pathologic stage, disease site, and complications were similar in both groups. No significant difference in the overall incidence of recurrent disease at two years was found between patients treated with either DTIC or L-PAM (22% vs 16%, respectively; P = .28). Patients who had perfusion with L-PAM, however, had a lower incidence of in-transit metastasis and recurrence at the scar than those having DTIC therapy (4% vs 12%, P = .06) at two years of follow-up. This preliminary report suggests that L-PAM may be more effective than DTIC in controlling scar recurrences and in-transit metastasis. Continued follow-up of this series of patients, with further analysis of patterns of recurrence and disease-free and overall survival at five years, will be necessary to better define the relative efficacy of L-PAM and DTIC in isolated limb perfusion.
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PMID:Isolated limb perfusion for stage I melanoma of the extremity: a comparison of melphalan and dacarbazine (DTIC). 276 4

The effects of heat and the interaction between hyperthermia and alkylating agents, such as cisplatin (CDDP) and melphalan (L-PAM) in human malignant melanoma biopsies have been investigated by a short-term assay based upon the inhibition of 3H-thymidine incorporation. Cell suspensions from 50 cutaneous and lymph nodal metastases were heated at 40.5 degrees C or at 42 degrees C for 1 h. There were significant antiproliferative effects due to heat in 10% of the tumors exposed to 40.5 degrees C and 34% to 42 degrees C. Thermal resistance was evident in 73% (at 40.5 degrees C) and 54% (at 43 degrees C) of tumors, and there was significant enhancement of cell growth in 17% and 12% of tumors. The combined effects of hyperthermia and drugs were studied on 36 tumors. Cell suspensions were exposed to different concentrations of CDDP or L-PAM for 1 h at 40.5 degrees C and 42 degrees C. Synergy between heat and CDDP was observed in 7% of cases treated with the lowest drug dose and 38% of cases treated with the highest (40.5 degrees C), with only a slight increase in the frequency of synergy at 42 degrees C. Synergy between heat and L-PAM was also observed in 12% to 44% of tumors at 42 degrees C as a function of drug concentration.
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PMID:Antitumor activity of hyperthermia alone or in combination with cisplatin and melphalan in primary cultures of human malignant melanoma. 280 74

A prospective randomized study was carried out to evaluate the effectiveness of additional regional cytostatic perfusion of the extremities in patients with malignant melanoma. In a control group (n = 54), the tumors were widely excised, and regional lymph nodes were dissected. The patients in the perfusion group (n = 53) received additional hyperthermic (42 degrees C) perfusion with Melphalan. The disease-free survival time was chosen as the criterion for evaluation. An intermediate analysis revealed a highly significant difference between the 2 groups (21 recurrences in the control group and 4 recurrences in the perfusion group, p less than 0.001). Therefore, the study was discontinued prematurely. In an analysis of the data performed after a median observation time of 5 years and 11 months, 26 recurrences were diagnosed in the control group, whereas 6 recurrences were noted in the perfusion group (p less than 0.001). The retrospective breakdown into different risk groups according to tumor thickness also demonstrates a significant difference. For patients with a primary tumor of 1.5-3.0-mm in thickness, 2 of 25 in the perfusion group and 10 of 25 in the control group have relapsed. For those with a primary tumor of greater than 3.0-mm in thickness, 4 of 28 in the perfusion group and 16 of 29 in the control group have relapsed. Eleven patients in the control group and 3 patients in the perfusion group have died due to metastatic spread of the melanoma (p less than 0.01). The results most clearly demonstrate the benefits of additional hyperthermic cytostatic perfusion.
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PMID:Hyperthermic perfusion with chemotherapy for melanoma of the extremities. 225 58

Melphalan (L-phenylalanine mustard) is a bifunctional alkylating agent that is commonly administered orally to treat a wide variety of malignancies, including cancers of the breast and ovary, as well as multiple myeloma. Although commercially available in Europe and Canada, intravenous (IV) melphalan remains investigational in the United States. The role of IV melphalan in cancer chemotherapy is not well defined, despite its manageable toxicity and higher and more predictable blood levels following IV administration compared with oral administration. In addition, unlike oral melphalan, an extensive phase I evaluation of IV melphalan has not been undertaken. At lower doses (eg, 30 to 70 mg/m2), both as a single agent and in combination, the activity of IV melphalan has been evaluated in only a limited number of diseases. However, striking activity has been observed in previously untreated patients with rhabdomyosarcoma, a disease not generally considered responsive to alkylating agents. When administered at high doses (greater than 140 mg/m2) requiring bone marrow reinfusion, melphalan effects a high response rate (but no improvement in survival) in a variety of nonhematologic tumor types, including resistant tumors such as melanoma and colon carcinoma. In contrast, in poor-prognosis patients with non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma, or neuroblastoma, high-dose melphalan-containing regimens have yielded both high response rates and improved survival, despite considerable toxicity. Additional clinical trials will be necessary to define the spectrum of activity of lower doses of IV melphalan and to define subgroups of patients most likely to benefit from high-dose melphalan.
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PMID:The systemic administration of intravenous melphalan. 305 5

In spite of the better results observed during the last decades and particularly due to earlier diagnosis and earlier surgical excision, malignant melanoma remains a tumour with a disconcerting course. This relative therapeutic impotence explains the variety of treatments used, including chemotherapy, radiotherapy, immunotherapy, etc. Surgical excision after chemotherapy under hyperthermic regional perfusion with extracorporeal circulation is an original method which has been applied for more than 3 decades with conflicting results but which may prove useful in several circumstances. The principle of regional perfusion using cytostatic drugs injected into the regional arterial blood flow resulted from a study by Klopp et al. in 1950. This technique was developed in practice by Creech et al. in 1957, and it was improved about 10 years later by additional hyperthermia, an idea suggested by Cavaliere et al. and by Stehlin. In Strasbourg, we have been using this method since January, 1982. Indications for perfusion are melanoma of the limbs with Breslow thickness greater than or equal to 0.85 mm, but from 1984 onwards these indications have been limited to patients with high-risk tumours such as melanoma with a Breslow thickness greater than or equal to 1.5 mm. Such melanomas are situated on the upper limb below the brachial insertion of the deltoid muscle, and on the lower limb below the upper third portion of the thigh. The technique consists of regional chemotherapy of the limb using extracorporeal circulation with hyperthermic perfusion. Melphalan is the drug used, and its dosage is based on body-weight: 1.4 mg/kg for the lower limb, and 0.9 mg/kg for the lower limb. Melphalan is introduced in the perfusion when the subcutaneous temperature near the tumour reaches 38 degrees C. The temperature of the limb is maintained at 40-42 degrees C for 45 minutes. At completion of the perfusion a wash-out is performed, and the tumour is excised with a 3 cm margin. From January, 1982 to January, 1987, 68 patients with malignant melanoma were treated by this method. Perfusion could not be performed in 5 patients because the small caliber of the vessel did not allow sufficient perfusion flow rate. No lethal complication occurred, and morbidity was very low.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Surgical treatment of malignant melanoma of the limbs combined with thermochemotherapy under extracorporeal circulation]. 319 54

Survival curves and dose escalation studies of four representative human tumor cell lines exposed to the various alkylating agents are presented. With HN2, at a level of one log of cell kill there was a fivefold range in drug concentration required to achieve this degree of cell kill among the cell lines, from 4.5 microM for the SL6 lung adenocarcinoma to 22 microM for the SW2 small-cell lung carcinoma. Four logs of SCC-25 squamous carcinoma cells were killed by 100 microM CDDP; however, there was only about one log of SL6 cells killed by 500 microM CDDP. To kill one log of G3361 melanoma cells required 24 microM 4-HC and to kill one log of SCC-25 cells required 24 microM, approximately a 16-fold difference. The curves for cell kill by L-PAM appeared to be biphasic, with a break at about 100 microM. There was about a threefold range in drug concentration required to achieve one log of cell kill with L-PAM, from 60 microM in the SCC-25 cell line to 18 microM in the SW2 line. To kill one log of SCC-25 cells required 295 microM BCNU and to kill one log of SW2 cell required 120 microM, about a 2.5-fold difference. The range of maximally tolerated HN2 concentrations were from 1200 microM for the SL6 cell line, 48 times the initial concentration, to 300 microM for the SCC-25 line, 16 times the initial concentration. The G3361 line tolerated the highest level of CDDP, 1900 microM, 48 times the initial concentration. The SCC-25 line, on the other hand, tolerated only 600 microM, 30 times the initial concentration. The SL6 cell line maximally tolerated 36 times the initial concentration of 4-HC (1450 microM), whereas the SCC-25 cell line tolerated only 18 times the initial concentration (720 microM). The G3361 melanoma tolerated 1555 microM, 30 times the initial concentration of L-PAM, and the SCC-25 cell line tolerated 700 microM, 14 times the initial concentration. The SL6 cell line tolerated the highest concentration of BCNU, 4200 microM, 24 times the initial concentration. The SCC-25 cell line tolerated 1450 microM, 8 times the initial concentration. In all cases, the SCC-25 cell line was least able to tolerate exposure to increasing concentrations of alkylating agents. The SL6 and G3361 cell lines showed the greatest tolerance for increasing concentrations of alkylating agents.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Development of alkylating agent-resistant human tumor cell lines. 337 Jul 36

The aim of this paper is to evaluate the effectiveness of DTIC when employed at a local level in hyperthermic antiblastic perfusion (HAP) for stage IIIA-IIIAB melanoma patients. Twenty-seven consecutive patients have been treated at the National Cancer Institute of Milan from October 1983 to June 1985. All the patients were submitted to HAP at 40 degrees for 60' with DTIC at the dosage of 2.5 g/m2 [corrected] for lower extremities and 1.5 g/m2 [corrected] for upper extremities. We observed a complete local response in three patients and a partial local response 50% in seven patients, 10 patients has a response less than 50% and 4 patients did not show any response. After surgical removal of the residual tumor when possible, 14 patients are alive without detectable disease while 11 are alive with disease and two dead for progression. No serious complications were observed. These data indicate that DTIC seems able to obtain in HAP, results superimposable to L-PAM without any significant toxicity.
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PMID:Hyperthermic antiblastic perfusion with DTIC in stage IIIA-IIIAB melanoma of the extremities. 355 93

Melphalan-induced DNA cross-linking was compared in a human melanoma cell line (RPMI 8322) and in phytohaemagglutinin (PHA)-stimulated lymphocytes. In both cell types a delayed induction of DNA cross-links was observed, with maximum DNA cross-linking occurring 6-12 hours after drug exposure. Significantly higher peak levels of DNA cross-links were found in PHA-stimulated lymphocytes, total DNA cross-linking being 2.5 times and DNA interstrand cross-linking 2.2 times higher. The intracellular content of free melphalan was 1.3-fold higher in RPMI 8322 cells, thus the lower DNA cross-linking was not due to a lower drug concentration in these cells. RPMI 8322 cells had a 1.8-fold higher level of glutathione, possibly indicating a higher capacity of these cells to inactivate melphalan.
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PMID:Melphalan-induced DNA cross-linking in human melanoma cells and phytohaemagglutinin-stimulated lymphocytes in relation to intracellular drug content and cellular levels of glutathione. 356 89


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