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

Twenty-nine patients with metastatic malignant melanoma were treated with cyclocytidine, 240 mg/m2/day sc for 10 days. All partients had received extensive prior chemotherapy. Only one patient achieved a partial remission; the overall response rate (complete plus partial) was 4%. Unusual toxic effects associated with cyclocytidine chemotherapy included the delayed onset of thrombocytopenia, orthostatic hypotension, and jaw pain.
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PMID:Cyclocytidine chemotherapy for malignant melanoma. 7 91

A phase I investigation of chlorozotocin, a new-water soluble chloroethylnitrosourea, was undertaken to define its pharmacologic effects in man. Forty-three patients received single intravenous doses ranging from 5 to 175 mg/m2 every 6 wk. No signs of toxicity were observed at doses of under 120 mg/m2, but thrombocytopenia occurred at higher doses. The thrombocytopenic nadir appeared to be dose-dependent and occurred 4 wk after treatment. Platelet transfusions were required in 2 patients who had previously received intensive chemotherapy. No significant leukopenia occurred. A mild reversible and delayed elevation of hepatic transaminases was found in 25% of courses of 120 mg/m2 or more. No renal toxicity was observed and gastrointestinal toxicity was mild. Investigation of clinical pharmacology revealed a rapid triphasic plasma clearance with initial t1/2S of 3, 15, and 30 min. The concentration of N-nitroso intact drug at 1 hr was 10% of the initial peak level. Renal excretion accounted for half of the dose. No significant concentration of N-nitroso intact or radiolabeled drug was detected in the cerebrospinal fluid of 2 patients in whom it was examined. There were objective signs of therapeutic activity in 5 patients, 3 of whom had melanoma. Based on these studies, the recommended dose for phase II investigation of chlorozotocin is 120 mg/m2 every 6 wk.
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PMID:Phase I studies on chlorozotocin. 14 44

In a phase II trial, prednimustine was often efficient in treating chronic lymphoid leukaemia (CLL) patients and was also active in some patients with lymphosarcoma, melanoma and bronchus carcinoma. Tolerance was generally excellent, the most critical side effect being thrombocytopenia in the case of CLL.
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PMID:A phase II clinical trial of prednimustine. Clinical screening cooperative group of E.O.R.T.C. 32 10

Piperazinedione was administered in doses of 9 or 12 mg/m2 by iv infusion every 3 weeks in 28 patients with previously treated malignant melanoma. Of the 25 evaluable patients, 72% had drug-induced toxicity: 40% had leukopenia, 56% had thrombocytopenia, 40% had anemia, and 16% had nausea and vomiting. None of these patients had partial remission, two had stable disease, and the remaining 23 had definite progression of their disease in spite of adequate trial with this agent.
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PMID:Piperazinedione in patients with advanced malignant melanoma: a Southwest Oncology Group study. 35 73

DDMP, a diaminopyrimidine folate antagonist, was given to 26 tumor patients in a dosage of 50 mg/m2 per week orally, simultaneously with 3 mg CF i.m. or i.v. The CF dose was increased to 30 mg in patients showing evidence of toxicity, and withdrawn in the absence of toxicity. The dose-limiting toxicity was seen in myelosuppression, particularly thrombopenia and skin rashes. At the 3 mg CF level, 18 out of 26 patients developed toxicity. No toxicity was seen at the 30 mg CF level in 11 patients. After cessation of CF, toxicity occurred in five out of seven patients. After the onset of toxicity, CF was added as a delayed rescue, in a dosage of 15 mg every 8 h or 30-60 mg daily. One patient died of sepsis with agranulocytosis. All other patients recovered from myelosuppression within 1 or 2 weeks. Objective responses were observed in seven patients, four of the ten with epidermoid cancer of the head and neck, two out of eight with epidermoid cancer of the lung, and one out of three with melanoma.
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PMID:Initial clinical experience with a simultaneous combination of 2,4-diamino-5(3',4'-dichlorophenyl)-6-methylpyrimidine (DDMP) with folinic acid. 37 10

Forty-one evaluable patients with malignant melanoma resistant to other chemotherapeutic agents received 9 mg/m2 of piperazinedione every 3 weeks. Two patients had partial responses and one additional patient had stable disease. One of the partial responses occurred in a patient with subcutaneous metastases and the other occurred in a patient with pulmonary and osseous metastases. Both antitumor responses occurred in the 17 patients with a performance status of greater than or equal to 80%. The dose-limiting toxicity was myelosuppression; thrombocytopenia was more frequently observed than granulocytopenia.
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PMID:Phase II trial of piperazinedione in malignant melanoma: a report by the Southeastern Cancer Study Group. 47 10

From June 1975 to August 1977, 19 patients with distant metastases of malignant melanoma of the skin that were no longer responsive to chemotherapy were treated with BCG given intravenously. A single dose of lyophilized Pasteur BCG ranging from 2 X 10(7) to 3 X 10(8) viable units was given in 500 ml of saline infused in 5 to 6 h. Seven of the 16 evaluable patients benefited from treatment; 3 showed an objective regression of more than 50% of the original tumor volume, and 4 an arrest of tumor growth. The objective regressions lasted from 2 to 5 months, and 1 case had an arrest of tumor growth for 29 months. The regression rate was related to the BCG dosage: 2 X 10(8) viable units appears to be the dosage that gives severe but reversible toxicity and is able to induce objective regression. The most responsive lesions were skin and subcutaneous deposits (5 of 7) and lung metastases (1 of 4). Toxic effects seem to be related to the number of bacilli injected. In the group of 10 cases treated with less than 10(8) units, toxicity was modest: 4 patients had fever (up to 38.5 degrees C) that lasted a few days, and in 3 cases it was associated with shivering during the infusion period and weakness. One case only had vomiting and jaundice. Toxicity was severe in the 9 patients that were treated with a dosage higher than 10(8): patients had fever and weakness for at least 4 days and shivering during the infusion. Two had adrenal insufficiency and 7 had liver enlargement and jaundice with return to normality by day 21. In the whole series 8 patients had leucopenia and 5 thrombocytopenia for 2 to 3 days: only 1 patient required blood and platelet transfusion. No significant variations in immunoglobulin levels were observed. No variations of PPD or BCG skin tests were observed after treatment. Three patients expired; the first treated with 6 X 10(7) unit, had an intercurrent disease (autopsy showed a heart infarction); the second, treated with 1.8 X 10(8), showed a rapid growth of lung metastases and died 15 days after treatment; the death of the third patient was probably due to anaphylactic shock. All 3 patients had been previously treated with BCG, given by scarification or intranodular injection.
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PMID:Intravenous administration of BCG in advanced melanoma patients. 68 66

Twenty-two patients with cutaneous metastases of malignant melanoma were treated with intralesional injections of the methanol extraction residue of bacillus Calmette-Guerin (MER). The local reaction consisted of erythema and pustule formation followed by ulceration and tumor necrosis. Side effects included fever, chills, headache and malaise in the majority of patients; nausea, vomiting, cyanosis and hypotension occurred infrequently. Hypersensitivity reactions were not observed. Temporary abnormalities in liver function were seen in 11 of 19 patients tested. Reversible lymphopenia and thrombocytopenia developed in 7 of 17 and 7 of 18 patients, respectively. Immune function, as measured by skin tests for delayed hypersensitivity and the in vitro response of isolated lymphocytes to mitogens and microbial antigens, was not influenced by treatment with MER. Transient increases were observed in total hemolytic complement, complement components and the reduction of nitroblue-tetrazolium by neutrophils. Eight of eighteen evaluable patients showed a complete disappearance of all injected lesions. We conclude that intratumoral injection of MER is effective treatment for cutaneous metastases of malignant melanoma, with a complete response rate comparable to that observed after intralesional injection of BCG.
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PMID:Intralesional injection of the methanol extraction residue of Bacillus Calmette-Guerin (MER) into cutaneous metastases of malignant melanoma. 72 66

The major toxic effects of DTIC are nausea and vomiting, leukopenia, and thrombocytopenia. It is an effective drug in the treatment of malignant melanoma with better response rates in women than in men. The addition of other drugs to DTIC therapy does not produce a higher response rate. Preliminary results indicate that as an adjuvant to standard surgical therapy DTIC does not appear beneficial to patients with a high risk for recurrence.
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PMID:Phase I evaluation of DTIC (NSC-45388) and other studies in malignant melanoma in the Central Oncology Group. 76 71

In a phase I study, the best antitumor/toxicity ratio for DTIC was reported to be at a dose of 250 mg/m2/day X 5 repeated at 28-day intervals. Nausea, vomiting, leukopenia, and thrombocytopenia were the major toxic effects noted. The best responses were seen in disseminated melanoma (19%), various sarcomas (22%), and Hodgkin's disease. A subsequent phase II study in refractory lymphomas showed a response rate in Hodgkin's disease of 56%. In disseminated melanomas, DTIC was then combined with vincristine and BCNU and demonstrated a response rate of 23% which did not improve with the addition of chlorpromazine (23%). A response rate of 31% was seen with the combination of DTIC, BCNU, and hydroxyurea which did not improve with the addition of vincristine (30%). Responders had a more significant survival rate as compared to nonresponders.
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PMID:DTIC (NSC-45388) studies in the southwest oncology group. 76 72


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