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)

Fifty patients with metastatic malignant melanoma were randomized to treatment with either DTIC (2 mg/kg/day X 10 iv) or the combination of BCNU (150 mg/m2 iv) plus vincristine (VCR) (2 mg/m2 iv on Day 1 only). Treatment failures were crossed over to the alternate therapy. Primary, secondary, and cumulative response rates to DTIC were 29%, 9%, and 22%, respectively. Primary, secondary, and cumulative response rates to BCNU plus VCR were 23%, 29%, and 25%, respectively. Five of 26 patients (19%) experienced objective regression from secondary therapy after failure to respond to primary therapy. DTIC produced gastrointestinal and hematologic toxic effects; BCNU plus VCR produced gastrointestinal, hematologic, and neurologic toxic effects. VCR administered at a dose of 2 mg/m2 resulted in excessive neurologic toxic effects in 12 of 21 patients; a maximum VCR dose of 2 mg/injection was well tolerated by 15 subsequent patients without an adverse effect upon response rate. An analysis of tumor burden and organ involvement in responders and nonresponders suggests that DTIC is the first-choice treatment for patients with limited tumor burdens and nonvisceral metastases; BCNU plus VCR is the first-choice treatment for patients with extensive tumor burdens and visceral-predominant disease. However, failure to respond to primary therapy does not preclude response to secondary therapy with the alternate regimen.
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PMID:Randomized prospective trial of DTIC (NSC-45388) alone versus BCNU (NSC-409962) plus vincristine (NSC-67574) in the treatment of metastatic malignant melanoma. 79 78

One hundred thirty two patients with disseminated malignant melanoma were treated using a combination of BCNU, vincristine and imidazole carboxamide. A response rate of 23% was observed, while 16% had stable disease. The patients' median survival was 42 months from diagnosis and 5.3 months from the onset of treatment. These results are not significantly different from therapy with imidazole carboxamide alone. Patients on this study were observed to have a significant reduction in the number of lymphocytes in their peripheral blood (mean 1800/mm3, median 1550/mm3). Patients with lymphopenia prior to the onset of therapy (86%) had a similar response rate but a shorter median survival (4.4 months vs. 7.8 months, P = .03) than patients with normal lymphocyte levels. These findings are compatible with recent observations on the importance of host immunocompetence in patients with malignant melanoma. Eosinophil levels were not closely correlated with response, although among patients with eosinophil counts of greater than 300/mm3 (22%), a slightly higher response rate (29%) was observed (P = .13). Eosinophilia did not influence patient survival.
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PMID:Combination chemotherapy with bis chloroethyl nitrosourea (BCNU), vincristine and dimethyl triazeno imidazole carboxamide (DTIC) in disseminated malignant melanoma. 83 24

Forty patients with disseminated malignant melanoma were treated with triple combination chemotherapy consisting of Imidazole Carboxamide, BCNU and Vincristine. Seventeen of 40 patients (42.5%) showed significant responses including three complete responses. Responses were seen in cutaneous, lymph node and pulmonary metastases. Nine instances of hepatic metastases were unaffected by therapy but 68% of the skin and nodal patients responded. The median response duration was only 4 months and the median survival of responders was 9.5 months compared to a 2 month median survival of non-responders. Half of the responders died of CNS metastases. The short duration of response, the resistance of hepatic metastasis and the high incidence of cerebral recurrence necessitate additional therapeutic approaches to this disease.
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PMID:Combination chemotherapy of malignant melanoma with imidazole carboxamide, BCNU and vincristine. 83 50

One hundred twenty-one patients with disseminated malignant melanoma were treated with BCNU, vincristine, DTIC, and chlorpromazine (BVD). A response rate of 22% was observed; 28% of the patients had stable disease and 50% had increasing disease. Similar response rates were obtained with both the high dose and low dose treatment schedules. Patients who exhibited some degree of improvement during their initial course of treatment had the highest overall response rate (72%) to BVD chemotherapy. The median survival from onset of therapy was six months for all patients and 18 months for patients who responded to chemotherapy. The median duration of response was 9.9 months. Thus, the addition of chlorpromazine to BVD chemotherapy did not increase tumor response, and the overall results obtained were comparable to DTIC alone. Patients were found to be lymphopenic prior to the onset of therapy. Their median absolute lymphocyte count was 1800/mm3. Those patients with absolute lymphocyte counts above the 2710/mm3 normal mean had significantly higher response rates (35% vs. 19%, P less than .05) and longer survivals (9.8 months vs. 4.3 months, P less than .05) than patients with lower initial lymphocyte levels. Pretreatment eosinophil and monocyte counts were not closely correlated with patient response or survival.
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PMID:Bis chloroethyl nitrosourea, vincristine, dimethyl triazeno imidazole carboxamide and chlorpromazine combination chemotherapy in disseminated malignant melanoma. 83 51

A 43-year-old man with metastatic malignant melanoma was treated with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in combination with imidazole carboxamide and hydroxyurea. He achieved complete remission. After 22 months of chemotherapy, the patient developed bilateral pulmonary infiltrates. Open lung biopsy showed sclerosing alveolitis. Long-term therapy with BCNU may cause pulmonary fibrosis, as has been seen with other cytotoxic drugs.
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PMID:Pulmonary fibrosis after prolonged therapy with 1,3-bis (2-chloroethyl)-1-nitrosourea. 89 Dec 93

Immunological investigations in malignant melanoma have demonstrated the important role of immunological defence mechanisms in the control of tumour growth and tumour spread. On the basis of the different test systems for investigation of immunecompetence and tumourspecific immunity it was possible to demonstrate that patients with melanoma, especially of clinical stages II and III, have a weak, sometimes an anergic immune reaction against their own tumour. The information obtained from in vitro and in vivo studies in human on tumour immunity formed the rational basis for immunotherapy in malignant melanoma. Increasing evidence suggests that active non-specific immunotherapy and, especially, active specific immune-stimulation with inactivated melanoma cells can delay the appearance of distant metastases and result in an improved survival rate for patients with involved regional lymph nodes. At present the use of involved chemotherapy is mostly confined to patients with disseminated malignant melanoma. The most extensively used chemotherapeutic agent for treatment of melanoma is the DTIC (dimethyl-triaceno-imidazole-carboxamide). The objective response rate with this monotherapy has been reported to be up to 25%. Nitrosoureas (BCNU, CCNU, MECCNU) have also been widely used and have brought clinical responses similar to DTIC. Experimental studies in animal models and investigation in human have demonstrated that chemotherapy can be combined successfully with immunotherapy with a potential additive, perhaps synergistic, effect.
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PMID:[Immunology and therapy of malignant melanoma (author's transl)]. 90 25

A total of 270 patients with metastatic malignant melanoma were entered into a randomized chemotherapy study conducted by the Central Oncology Group (COG) over a period of 2 years (COG protocol No. 7130). The study utilized DTIC, CCNU, BCNU, vincristine, and hydroxyurea. The results of therapy with DTIC alone were compared with three combinations: (a) DTIC, CCNU, and vincristine; (b) DTIC, BCNU, and vincristine: and (c) DTIC, BCNU, and hydroxyurea. There were 243 evaluable patients out of 270. The response rate was 17.3% (42 of 243 patients) for evaluable patients and 15.5% (42 of 270 patients) for all patients entered in the study. The results showed no statistically significant difference in the response rates among the four treatment arms. However, several significant points were observed: (a) A 13% response rate was obtained using a combination of agents that included DTIC in patients who had previously shown no response to DTIC used as a single agent. (b) There was a significant difference in survival time when comparing responders to those with no change and to those with progression. (c) Toxicity was noted to be greater in responders than in nonresponders. (d) Two of the four treatment arms were considered most advantageous due to the ease of administration. These treatment arms were DTIC, BCNU, and vincristine and DTIC, CCNU, and vincristine administered in 5-day courses every 6 weeks. (e) The percentage of response and length of survival were significantly greater in patients without brain or liver metastasis. (f) In comparing men to women there was no statistically significant difference in response in rates or durations of response. (g) There was no statistically significant difference in survival when comparing site of primary lesion.
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PMID:DTIC (nsc-45388) and combination therapy for melanoma. I. Studies with DTIC, BCNU (NSC-409962), CCNU (NSC-79037), vincristine (NSC-67574), and hydroxyurea (NSC-32065). 99 Nov 49

The therapeutic results of a controlled study with three multiple-drug regimens (regimen A: DTIC, vincristine, BCNU; regimen B: DTIC, vincristine, hydroxyurea; and regimen C: DTIC, actinomycin D, BCNU) in a total of 274 evaluable patients with advanced malignant melanoma are reported. CRs were significantly more frequent (P less than 0.01) in regimens A (9.3%) and C (16.4%) compared with regimen B (1.1%). No significant difference in terms of CR plus PR was detected among the three regimens. In all regimens a higher number of CRs plus PRs was seen in patients with soft tissue metastases only, compared with those who had visceral involvement. In all three regimens patients achieving CR showed a longer duration of response and survival in comparison with patients achieving PR. The incidence of brain metastases was neither lowered nor delayed by the presence of BCNU in regimens A and C.
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PMID:Comparative evaluation of three combination regimens for advanced malignant melanoma: results of an international cooperative study. 100 May 18

BCNU, hydroxyurea, and imidazole carboxamide (DTIC) were administered to 89 patients with disseminated malignant melanoma. A response rate of 27% was observed. The addition of vincristine in another 89 patients did not significantly improve the response rate (30%). This includes patients who died during or after one course of therapy (less than 28 days). If the early deaths are not considered, the over-all response rate was 38%. (he best responses occurred in patients with skin, lung, and/or lymph node involvement. Liver and brain involvement heralded poor responses. This response rate appeared to be independent of age, sex or previous therapy. Moderate and severe toxicity, predominantly nausea and vomiting, was noted in most patients. The median survival for all evaluable patients was 17 months, and was independent of the regimen used.
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PMID:Combination chemotherapy for disseminated malignant melanoma. 111 12

One hundred twenty patients with inoperable metastatic malignant melanoma were randomly allocated to treatment with either a combination of BCNU 150 mg/m2 and vincristine 2 mg/m2 given every 30 days, or one of two regimens of DTIC: 300 mg/m2/day x 6 or 100 mg/m2/8 hours x 18 given every 30 days. Eight of the 51 (16%) patients who were originally treated with the BCNU and vincristine combination had 50% or more objective tumor regression, compared to 6 out of 25 (24%) patients treated with daily injections of DTIC, and 6 out of 21 (29%) patients treated with DTIC injections every 8 hours. The median duration of response to the BCNU and vincristine combination was 60 days, and the median duration of survival from initiation of treatment was 6.5 months in the responders and 3.3 months in the nonresponders. The median duration of response was 90 and 100 days for the daily and 8-hour regimens of DTIC respectively, andthe median duration of survival from commencement of treatment was 8.5 months for the responders and 3.5 months for the nonresponders. None of the 43 patients who failed to respond to the initial treatment program or whose disease progressed after initial improvement responded to the alternate treatment regimen.
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PMID:Comparison of the combination of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and vincristine with two dose schedules of 5-(3,3-dimethyl-1-triazino) imidazole 4-carboxamide (DTIC) in the treatment of disseminated malignant melanoma. 111 13


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