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)

The unavailability of effective treatment of metastatic hormone refractory prostatic carcinoma warrants trials of new and promising treatments. Coumarin is an investigational new drug that has produced objective tumor regression in some patients with metastatic renal cell carcinoma and malignant melanoma. Coumarin has shown activity against prostatic carcinoma in the Dunning R-3327 rat prostatic adenocarcinoma model. Forty-eight patients with metastatic hormone naive (5 stage D1 and 10 stage D2) or hormone refractory (33 stage D3) prostatic carcinoma of average age 67.6 years (range 46-86) and ECOG performance status of 2 or better were given 3 grams coumarin daily by mouth and evaluated monthly for toxicity and response by rigid criteria in a multicenter trial. Toxicity was limited to asymptomatic SGOT elevations in 3 patients and nausea and vomiting in 4 patients that required cessation of therapy in 2. Eligibility and protocol violations removed 6 additional patients from response evaluation. There were no complete responses. Partial responses (3 of 40 patients, 8%) occurred in 2 patients with bidimentionally measurable disease and 1 patient with disease evaluable by bone scan and elevated prostate specific antigen and prostatic acid phosphatase. The remaining patients progressed after 1 to 12 (average 4.4) months. Coumarin is a relatively nontoxic drug that may warrant further trials in a subset of patients with prostatic carcinoma.
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PMID:Phase II evaluation of coumarin (1,2-benzopyrone) in metastatic prostatic carcinoma. 154 51

The antiemetic activity of two different high doses and schedules of metoclopramide in dacarbazine-treated cancer patients was compared in a double-blind crossover study. Regimen A consisted of metoclopramide [2 mg/kg x 4 intravenously (i.v.)] plus methylprednisolone (250 mg x 2 i.v.) plus diphenhydramine (50 mg x 2 i.v.). Regimen B consisted of metoclopramide (3 mg/kg x 2 i.v.) plus dexamethasone (20 mg i.v.) and diphenhydramine (50 mg i.v.). Both treatments were administered for the first 2 days of 5-day dacarbazine chemotherapy. Thirty-two patients (13 men and 19 women) affected by melanoma and sarcoma were entered in the study. Complete protection against nausea and vomiting for the first 2 days of chemotherapy in both antiemetic regimens was not significantly different. Patient preference and tolerance of the two antiemetic treatments were similar. Regimen B, employing a lower dosage of metoclopramide and steroids and using a more simple schedule of administration should be the preferred treatment.
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PMID:Antiemetic activity of two different high doses and schedules of metoclopramide in dacarbazine-treated cancer patients. 155 97

Melanoma frequently disseminates to the gastrointestinal tract, being found post-mortem in 60 per cent of patients with disseminated disease, while during life it is diagnosed in only 4 per cent. During the period 1981-87, 835 melanoma patients were referred and 30 developed complaints caused by gastrointestinal metastatic melanoma. Twenty-three patients were treated surgically. The interval between treatment of the primary melanoma and detection of intestinal involvement was a median of 34 months (range 2-87 months). In four patients recurrence in the gut was the first evidence of dissemination. Major complaints were nausea and vomiting, abdominal pain, signs of anaemia, and blood in the stools. Complications were bleeding (ten cases), ileus due to intussusception (five cases), bowel perforation (four cases) and cholecystitis (one case). The metastases, mainly localized in the small bowel, were removed by relatively simple procedures. Symptoms were reduced in 19 patients. Two patients died after operation: one from sepsis due to suture leakage, the other from pneumonia and a cerebrovascular accident. Of the remaining patients, 16 survived a median of 7.5 (range 0.7-32.0) months. Five patients are still alive 72, 72, 70, 7 and 2 months after the metastasectomy, three of whom are tumour-free. The actuarial 5-year survival of all patients is 19 per cent. These results support surgical intervention for patients with complaints and/or complications attributable to gastrointestinal metastatic melanoma.
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PMID:Surgery for melanoma metastatic to the gastrointestinal tract. 168 96

We report the results of a phase II evaluation of carboplatin (CBDCA) in 45 patients with advanced malignant melanoma. Of the 43 evaluable patients, 6 had been treated previously with chemotherapy; 11 had been treated with immunotherapy. The initial dose was 400 mg/m2 i.v. every 4 weeks; the dose was modified as required to achieve moderate myelosuppression. There was one complete response (duration 16 months) and six partial responses, for a major objective response rate of 16%. Toxicity consisted primarily of acute nausea and vomiting, and thrombocytopenia. The activity of CBDCA in this disease is similar to that of cisplatin and dacarbazine.
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PMID:Phase II trial of carboplatin in patients with advanced melanoma. 169 68

Temozolomide (CCRG 81045: M&B 39831: NSC 362856) is an analogue of mitozolomide displaying similar broad spectrum activity in mouse tumours, but showing considerably less myelosuppression in the toxicology screen. Temozolomide was initially studied intravenously at doses between 50-200 mg m-2 and subsequently was given orally up to 1,200 mg m-2. A total of 51 patients were entered on the single dose schedule. Temozolomide exhibits linear pharmacokinetics with increasing dose. Myelotoxicity was dose limiting. Experimentally, temozolomide activity was schedule dependent and therefore oral administration was studied as a daily x 5 schedule between total doses of 750 and 1,200 mg m-2 in 42 patients. Myelosuppression was again dose limiting. The recommended dose for Phase II trials is 150 mg m-2 po for 5 days (total dose 750 mg m-2) for the first course, and if no major myelosuppression is detected on day 22 of the 4 week cycle, the subsequent courses can be given at 200 mg m-2 for 5 days (total dose 1 g m-2) on a 4 week cycle. Mild to moderate nausea and vomiting was dose related but readily controlled with antiemetics. Clinical activity was detected using the 5 day schedule in four (2CR, 2PR; 17%) out of 23 patients with melanoma and in one patient with mycosis fungoides (CR lasting 7 months). Two patients with recurrent high grade gliomas have also had partial responses. Temozolomide is easy to use clinically and generally well tolerated. In the extended Phase I trial temozolomide only occasionally exhibited the unpredictable myelosuppression seen with mitozolomide.
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PMID:Phase I trial of temozolomide (CCRG 81045: M&B 39831: NSC 362856). 173 31

In two pilot studies, 55 patients with symptomatic metastases from malignant melanoma were treated with irradiation and concurrent cisplatin. In the first group, cisplatin was given as a continuous intravenous infusion of 20 mg/m2 per day on days 1-5 and 22-26, with irradiation on days 2, 5, 9, 16, 23 and 26. The second group received 20 mg cisplatin over 24 h commencing 1 h before each fraction of irradiation on days 1, 4, 8, 11, 15 and 18. The first series of 28 patients had 30 lesions treated. Nine (30%) of these lesions responded completely and 10 (33%) achieved partial response for an overall response rate of 63% (95% confidence interval 44-80%). Survival was not evaluated in this group. The second group was comprised of 27 patients, with one irradiated lesion each. 1 patient achieved a complete response and 13 (48%) a partial response for an overall response rate of 52% (32-71%). Median survival was 21 weeks (16-31 weeks). Treatment was well tolerated with nausea and vomiting being the most common toxicity. Synchronous cisplatin infusion with radiotherapy achieves high response rates in metastatic melanoma. Whether it is superior to radiotherapy alone will require evaluation in a randomised trial.
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PMID:Synchronous cisplatin infusion during radiotherapy for the treatment of metastatic melanoma. 178 64

Forty-six patients with refractory solid malignancies received the new platinum complex [2,2-bis(aminomethyl)-1,3-propanediol-N-N'] [1,1-cyclobutanedicarboxylato] [(2-)0,0')] platinum (zeniplatin). Zeniplatin was given, without hydration or mannitol, as a 60- to 90-min i.v. infusion every 3 weeks at doses ranging from 8 to 145 mg/m2. The maximum tolerated dose of zeniplatin was 145 mg/m2. The dose-limiting toxicity of zeniplatin was dose-related leukopenia and neutropenia, with the nadir usually observed between 1 and 2 weeks after therapy and recovery usually occurring by 3 weeks after therapy. Thrombocytopenia was rare. The most prominent non-hematological side-effect of zeniplatin was nausea and vomiting. Other non-hematological side-effects were mild or absent. Zeniplatin did not induce significant neurological or auditory toxicity. Zeniplatin was not nephrotoxic at doses less than or equal to 120 mg/m2. At 145 mg/m2, the clearance decreased by a mean of 40% after 2 cycles of therapy. Two patients, one with malignant melanoma and one with renal cell cancer, achieved a partial response. Pharmacokinetics of free (plasma ultrafiltrates) and total platinum in plasma were determined in 5 patients. An in vitro study of the rate and extent of zeniplatin binding to protein in human plasma was also performed. Free and total platinum were measured by flameless atomic absorption spectrometry; free zeniplatin was measured in ultrafiltrate by HPLC. Total and free plasma platinum concentrations were co-modelled using the information from the in vitro study.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase I clinical and pharmacokinetic study of zeniplatin, a new platinum complex. 179 26

A combination chemotherapy including vinblastine (6 mg/m2 i.v. days 1-2), BCNU (100 mg/m2 i.v. day 3), and cisplatin (50 mg/m2 i.v. day 5) was given as salvage treatment in 46 consecutive, previously treated patients affected by metastatic malignant melanoma. Courses were planned every 4 weeks provided that a complete bone marrow recovery occurred, otherwise they were delayed for 1-2 additional weeks. Objective responses (3 CRs and 10 PRs) were observed in 13/46 (28%) patients; 12 cases had stable disease and 21 patients progressive disease during treatment. Median duration of response was 13 months (range, 5-18), and median survival was 11 months (range, 3-20) for all patients. Nausea and vomiting were the most distressing side effects, whereas a grade I leukopenia caused a delayed treatment in 90% of patients. In conclusion, the combination chemotherapy was moderately toxic and did not seem to give substantially better results than obtained with other reported regimens.
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PMID:Combination chemotherapy with vinblastine, BCNU and cisplatin in advanced malignant melanoma. 186 48

Didemnin B is a depsipeptide extracted from the marine tunicate Trididemnin cyanophorum. This agent is a potent inhibitor of L1210 growth in vitro and has activity against murine B16 melanoma, P388 leukemia, and M5076 sarcoma in vivo. The results of preclinical toxicologic tests demonstrated abnormalities in clotting parameters thought to be secondary to drug-induced liver dysfunction. Thirty-five patients with advanced cancer received didemnin B according to a 5-day bolus schedule with dose levels ranging from 0.03 to 2.00 mg/m2/d. The dose-limiting toxicity was nausea and vomiting. Sporadic elevation of the hepatic enzyme level occurred but was not dose limiting. Two patients had anaphylactic symptoms possibly related to the 5% polyoxyethylated castor oil (Cremophor EL, BASF, Ludwigshafen, Germany) vehicle during the drug infusion. Clinical bleeding was not observed and myelosuppression was not significant. No partial or complete tumor responses were seen. The recommended Phase II dose for the 5-day schedule is 1.6 mg/m2/d.
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PMID:A phase I clinical trial of didemnin B. 193 1

A phase I trial of piritrexim was conducted by use of a prolonged, low-dose oral schedule. A number of different regimens were tested, including daily dosing for 21 days followed by 7 days of no drug therapy; continuous dosing; and daily dosing for 5 of 7 days for 3 consecutive weeks followed by a week of rest. Dose escalation was accomplished by increasing the dosing frequency from once a day to twice a day and then to three times a day and by increasing the number of days of administration. Fifty-one patients with advanced cancer were entered in the study. One hundred twenty-four (96%) of 129 courses were considered assessable. Myelosuppression proved to be the dose-limiting toxic effect. Other toxic effects included stomatitis, nausea and vomiting, anorexia, diarrhea, skin rash, fatigue, and elevation of liver transaminase levels. Antitumor activity was observed in patients with melanoma and bladder cancer, and disease stabilization occurred in those with sarcoma and pheochromocytoma. The recommended dosing schedule for phase II clinical trials is 25 mg three times a day for 5 days for 3 consecutive weeks followed by 1 week of no drug therapy.
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PMID:Phase I trial of piritrexim capsules using prolonged, low-dose oral administration for the treatment of advanced malignancies. 198 18


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