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)

Maytansine, a new ansa macrolide antitumor antibiotic, was administered to 60 patients as part of a phase I study. The doses given ranged from 0.01 (starting level) to 0.9 mg/m2 for 3 days. The toxic effects encountered consisted principally of nausea, vomiting, diarrhea, and occasionally, stomatitis and alopecia. Superficial phlebitis was also encountered and occurred when the drug was diluted in a volume of less than 250 ml. Myelosuppression occurred infrequently; it was almost regularly associated with abnormal liver function tests. Antitumor activity was detected in one patient each with melanoma, breast carcinoma; and head and neck clear cell carcinoma. Further studies are indicated with this compound since it has shown evidence of activity with little or no myelosuppression.
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PMID:Phase I study of maytansine using a 3-day schedule. 34 10

Sixty adult patients with disseminated melanoma refractory to DTIC or Dacarbazine were given chemoimmunotherapy with intermittent high single dose Actinomycin-D and Levamisole. Actinomycin-D was given at a dose of 1.5-2.0 mg/m2 intravenously every 3 to 4 weeks. Levamisole was given in a dose of 150 mg/day for two consecutive days each week (50 patients) and in a dose of 200 mg every other day (10 patients). Antitumor responses consisted of 2% complete remissions (CR), 2% partial remissions (PR), and 33% disease improvement less than PR or stabilization (S). Comparison of these patients who received Actinomycin-D + Levamisole with those on an immediately preceding study in a similar population where Actinomycin-D was given as a single agent revealed no difference in response rates. Patients who responded to Actinomycin-D + Levamisole (CR + PR + S) survived significantly longer (35 weeks) than nonresponders (12 weeks, p less than 0.01). Survival was not longer (p less than .05) in responding patients (CR + PR + S) receiving Actinomycin-D + Levamisole (35 weeks) compared to those responding to Actinomycin-D alone (18 weeks, p = 0.09). Hematologic toxicity was tolerable with median lowest granulocyte counts of 1.6 x 10(3)/microliter and platelet counts of 134,000/microliter. Other toxic effects were predominantly nausea, vomiting, and mucositis. In those patients who received alternate day Levamisole there was greater gastrointestinal upset as well as fever, rash and central nervous system toxicity which was unacceptable.
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PMID:Actinomycin-D, levamisole chemoimmunotherapy of refractory malignant melanoma. 44 22

A phase I study of 4'-epi-Adriamycin (4'-epi-ADM) was performed in 22 patients with various types of advanced solid tumors. Very preliminary results would indicate that the drug produces a pattern of acute toxicity which is similar to that of Adriamycin. However, the incidence of vomiting, alopecia, and marrow suppression was less pronounced than that of Adriamycin. 4'-Epi-ADM prolonged the systolic time interval, although no patient presented clinical signs of cardiotoxicity. Two patients with renal carcinoma and malignant melanoma showed objective improvement. Present results suggest that further clinical studies with 4'-epi-ADM are indicated.
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PMID:Preliminary phase I study of 4'-epi-adriamycin. 45 33

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

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

Immunotherapy of malignant melanoma with BCG may be divided into two basic groups: 1. treatment of minimum residual disease. 2. direct intralesional application of BCG. In 19 patients with a histologically confirmed malignant melanoma, direct intralesional application of BCG was used to treat relapsing patients. In 10 of the 19 patients (group A) the relapse was confined to the primary region without signs of distant dissemination. In the remaining 9 patients (group B) signs of the lesion were present prior to BCG application. Our clinical and cytological evaluation bore on local reactions, systemic side reactions and response of non-injected lesions. In patients without signs of distant dissemination, local regression, characterized by a flattening and disappearance of lenticular metastases with scar formation, was achieved in 8/10 patients, while in the noninjected lesions, regression was noted in only 4/10 patients. In 4 patients of group A complete remission lasting 4-6 months was achieved. In the group of patients with signs of distant dissemination, local regression was observed in 6/9, while noninjected lesion regressed in only 1/9. Systemic response to BCG was characterized by febrile reactions with, in the majority of the patients, nausea till vomiting, muscular pain, pain of joints. In the majority of the patients the reaction passed away within 24 hr. A pretreatment with antipyretic and antihistaminic drugs proved of great help. The effect of BCG on the subsequent fate and survival of the patients is not discussed.
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PMID:Intralesional BCG application in malignant melanoma. 79 45

Asaley is an L-leucine derivative of sarcolysin which is more active against some rodent tumors. Studies in the USSR demonstrated activity in patients with ovarian and breast carcinoma, Hodgkin's disease, and multiple myeloma. This study in 73 evaluable patients indicated that an appropriate oral dose for patients with adequate bone marrow is 800 mg/M2/day X 4 days at 5-6 week intervals. The most common toxicities were myelosuppression, nausea, and vomiting. Antitumor activity was observed in 2 of 24 evaluable patients with melanoma, and stabilization of previously progressive disease was observed in patients with adenocarcinoma of the colon, multiple myeloma, lymphoma, breast carcinoma, and thyroid carcinoma. Responses were minimal and of short duration but most of the patients had received extensive prior therapy.
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PMID:Clinical evaluation of Asaley. 92 33

One hundred and nine adult patients with metastatic carcinoma were treated at 3-4-week intervas with a combination of adriamycin (40 mg/m2 given iv on Day 1) and cyclophosphamide (200 mg/m2/day given orally in divided doses on Days 3-6). Ninety-two of 96 patients who had an adequate trial (minumum of two courses or progression of disease after one course) had follow-up observations of tumor sites and were considered evaluable for response. Overall objective response rates by tumor type were as follows: stage III or IV ovarian adenocarcinoma, 61% (14 of 23 patients); endometrial adenocarcinoma, 67% (four of six patients); cervical adenocarcinoma, 33% (one of three patients); prostatic adenocarcinoma, 18% (two of 11 patients); testicular carcinoma, 33% (one of three patients); lung carcinoma, 21% (four of 19 patients); renal adenocarcinoma, 14% (one of seven patients); gastrointestinal adenocarcinoma, 18% (two of 11 patients); melanoma, 25% (one of four patients); and miscellaneous tumors, no responses in five patients. In patients with ovarian adenocarcinoma who had not previously received any cytotoxic chemotherapy the response rate was 80% (12 of 15 patients) with 33% five of 15 patients achieving complete clinical remission. CRs in these patients have now been maintained for periods ranging from 7 to 12 months. The major toxic effects were mild to moderate leukopenia, alopecia, and nausea with vomiting. Hemorrhagic cystitis was observed in three patients. The combination of adriamycin and cyclophosphamide is an effective treatment for carcinoma of the breast (reported elsewhere), ovary, and endometrium and should be considered for initial chemotherapy in patients with these tumors. Further investigations of its use for melanoma and carcinoma of the lung, prostate, kidney, and gastrointestinal tract are also warranted.
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PMID:Combination chemotherapy with adriamycin (NSC-123127) and cyclophosphamide (NSC-26271) for solid tumors: a phase II trial. 100 May 20

During the 9-year period from 1982 to 1991, 72 patients with melanoma were treated with a 5-day quadruple drug chemotherapy regime (BELD) comprising bleomycin, vindesine (Eldesine), CCNU (Lomustine) and DTIC. Forty-three patients had stage III melanoma, 34 of whom had evaluable disease. Of these 34, six (17.6%) achieved a complete response (CR), eight (23.5%) had a partial response (PR), five (14.7%) had stabilized disease (SD) and 15 (44.1%) had progressive disease (PD). Overall median survival of stage III melanoma patients was 38 weeks. Median survival of responders (CR + PR) was 47 weeks and 21 weeks for non-responders (SD + PD) (P < 0.005). Median follow-up time was 38 weeks. Following these encouraging results, 30 patients with stage II melanoma received BELD chemotherapy as adjuvant therapy after regional node dissection and clearance. Adjuvant BELD chemotherapy did not alter survival in these patients. BELD combination chemotherapy is well-tolerated, the main problems being nausea, vomiting, and leucopenia. We have maintained a combined response rate (CR + PR) of 41.1% for stage III disease. This is comparable with other combination chemotherapy regimes, which have as yet not been superseded by the newer biological therapies.
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PMID:Nine years' experience of BELD combination chemotherapy (bleomycin, vindesine, CCNU and DTIC) for metastatic melanoma. 128 72


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