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)

Seventeen patients with disseminated malignant melanoma were treated with DTIC (150 mg/m2, Days 1-5) and cyclocytidine (increasing doses sc, Days 1-10) in a phase I-II study. There was one early death. The remaining 16 patients were evaluable for response and toxicity. Two patients (13%) had CR lasting 8+ and 2+ months, while one patient (6%) had a PR lasting 1 month. Nausea and vomiting was seen in seven patients (44%), jaw pain in four (25%), and orthostatic hypotension in two (13%). Hematologic toxicity was not excessive, nor was it cumulative. The overall response rate of 19% was comparable to that reported with DTIC alone. This drug combination does not appear to offer any therapeutic advantage within the dosage range tested in disseminated malignant melanoma.
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PMID:Phase 1-11 study of DTIC and cyclocytidine in disseminated malignant melanoma. 6 23

A phase I-II study of cyclocytidine was conducted in 102 patients, 96 of whom had metastatic solid tumors and six of whom had acute leukemia. The drug was administered in 5- or 10-day courses of single daily iv or sc injections of 100-675 mg/m2 day. Two complete and six partial responses were observed in 64 solid tumor patients evaluable for response, 52 of whom had malignant melanoma or adenocarcinoma of gastrointestinal origin. The median duration of the responses was 6 months. An additional seven patients achieved stabilization of their disease for greater than or equal to 2 months. No responses occurred in six patients with acute leukemia. Side effects included nausea and vomiting, postural hypotension, and parotid pain, occurring in approximatley one third of patients receiving greater than 200 mg/m2/day. No myelosuppression was observed in six patients receiving 5-day courses of 100-200 mg/m2/day. Myelosuppressive toxicity became increasingly severe with doses greater than 200 mg/m2/day x 10, related at least in part to prior chemotherapy exposure including the nitrosoureas.
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PMID:Phase I-II evaluation of cyclocytidine. 6 28

Twenty-four patients with far advanced malignant tumors, resistent to established chemotherapy,, were treated with the combination of MNU and Cyclophosphamide. The drugs were administered in six-day cycles sequentially. MNU in doses of 4 mg/kg body weight and Cyclophosphamide in doses of 8 mg/kg body weight were given. Results of treatment showed response (greater than 50% tumor regression) in 10 (42%) of the 24 treated patients. Seven remissions were complete and three partial. Patients with Hodgkin's disease, malignant melanoma and breast cancer responded to this combination chemotherapy. Objective remissions were obtained also in five of thirteen patients with primary or metastatic brain tumors and in five of nine patients with pulmonary metastases. Nausea and vomiting were the main toxic effects, especially after injections of MNU. Myelosuppression was noted in about 50% of treated patients. Since this combination of cytostatics showed significant antitumor activity, further investigations are necessary on a larger number of patients and in other types of malignant tumors.
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PMID:Combination chemotherapy with 1-methyl-1-nitrosourea (MNU) and cyclophosphamide in solid tumors. 14 13

The compound 4'-(9-acridinylamino)methanesulfon-m-anisidide is a new derivative that was evaluated in a Phase 1 clinical trial. The schedule of drug administration consisted of daily i.v. injection for 3 consecutive days, repeated at 3-week intervals. Twenty-six patients received a total of 63 courses of 4'-(9-acridinylamino)methanesulfon-m-anisidide in a dose range from 4 to 50 mg/sq m/day. Hematopoietic toxicity was dose limiting, but it was of short duration and rapidly reversible. Mild nausea and vomiting were observed in 16% of the courses, and a mild degree of phlebitis was observed in 10% of the courses. Responses were observed in two patients with adenocarcinoma of the lung and one each of melanoma and acute myeloblastic leukemia. Phase 2 studies of 4'-(9-acridinylamino)methanesulfon-m-anisidide are planned at a starting dose of 40 mg/sq m/day for 3 days in good-risk patients and at 25 to 30 mg/sq m/day for 3 days in poor-risk patients. Course of treatment would be repeated at 21-day intervals.
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PMID:Phase 1 clinical investigation of 4'-(9-acridinylamino)methanesulfon-m-anisidide (NSC 249992), a new acridine derivative. 27 97

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

Twenty-six patients with disseminated malignant melanoma were treated with intermittent bolus DTIC and actinomycin D in an escalating dose schedule, starting at 650 and 1 mg/m2 respectively. Courses were repeated at 3--4-week intervals. Twenty four patients were evaluable for toxicity and 22 were evaluable for response. Two patients (9%) had a complete remission lasting 7+ and 14 months, and three patients (14%) had a partial remission lasting 2+, 5+, and 14+ months. Nausea and vomiting, lasting 24 hours, was observed in 88% of patients, while diarrhea was noted in 17%. Stomatitis and alopecia were less frequently observed. All responses occurred at nonmyelosuppressive doses and in patients with visceral-predominant metastases. This schedule offers the patient the convenience of single-day treatment and less prolonged gastrointestinal intolerance. Further evaluation of this drug combination and schedule would appear to be indicated.
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PMID:Phase I--II study of intermittent bolus administration of DTIC and actinomycin D in metastatic malignant melanoma. 35 80

Peptichemio is a peptide complex of m-L-phenylalanine mustard. A clinical evaluation of this agent was conducted in 116 patients, of whom 104 were evaluable for both toxicity and response. The majority of patients had solid tumors. The drug was administered iv daily for 3 days at doses of 20-75 mg/m2/day, with courses repeated at 3-4-week intervals. The optimal dose schedule appears to be 45 mg/m2/day for 3 days. The major side effects were cumulative myelotoxicity, phlebitis, and mild nausea and vomiting. No other major organ toxicity was observed. The partial remission rate was 7%. Most patients had received an alkylating agent as part of their previous therapy. There were seven partial responses and four less than partial responses achieved in patients with melanoma, lymphoma, and gastrointestinal, genitourinary, breast, and head and neck carcinomas. Responses lasted 4-36 weeks.
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PMID:Clinical evaluation of peptichemio. 37 97

Dianhydrogalactitol given iv in a schedule of 30 mg/m2/day for 5 consecutive days every 4 weeks was administered to 27 patients with metastatic malignant melanoma. All patients had received extensive prior therapy including chemotherapy and had progressive disease at the start of the study. Of 24 patients evaluable for response, 21 demonstrated progressive disease and three had stable disease for periods of from 4 to 11 months. No objective responses were observed. Two of the remaining three patients died 6 and 10 days after entry in the study, while the third refused to return after one drug course. Adverse effects included myelosuppression in eight patients, nausea and vomiting in five patients, and alopecia in one patient. Dianhydrogalactitol is considered to be insignificantly active in the secondary treatment of metastatic malignant melanoma at the dose and schedule studied.
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PMID:Phase II trial of dianhydrogalactitol in metastatic malignant melanoma: a Southwest Oncology Group study. 44 6

Twenty one patients with advanced metastatic melanoma were treated with a combination of 1-methyl-1-nitrosourea (MNU) and cyclophosphamide. All the patients had not previously been treated with cytostatics. MNU in the dose of 4 mg/kg and cyclophosphamide in the dose of 8 mg/kg body weight was administered daily. The drugs were given in 6 day cycles. Objective response (greater than 50% tumor regression) was obtained in 8 (38%) of the 21 treated patients, with 2 complete and 6 partial remissions. The duration of remission was 2--12 months (M = 6.2 months). Injections of MNU caused nausea and vomiting in approximately all the treated patients. Combination of these drugs, however, produced myelodepression in 33% of treated patients. This combination of drugs showed antitumor activity in metastatic malignant melanoma, particularly in melanoma metastasis of the lung, brain and lymph nodes and needs further investigation.
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PMID:Combination chemotherapy with 1-methyl-1-nitrosourea and cyclophosphamide in metastatic melanoma. 65 33

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


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