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)

Fotemustine is a novel chloroethylnitrosourea, that readily penetrates the blood brain barrier. Preliminary French studies reported encouraging results with fotemustine in patients with cerebral metastases of malignant melanoma. Thirty-one patients with histologically confirmed metastatic malignant melanoma were entered on a phase II trial. The treatment regimen consisted of fotemustine, administered intravenously as a rapid infusion, at a dose of 100 mg/m2 on day 1, 8 and 15 every 4 to 5 weeks. Objective response (CR + PR) was documented in 3 patients. Median time to treatment failure (TTF) was 44 days and median survival was 164 days. Life threatening toxicity did not occur; hematological toxicity and nausea and vomiting were the most common toxicities. Despite a somewhat disappointing response rate, objective responses were documented in patients with cerebral metastases. Since no other chemotherapeutic agent has shown therapeutic efficacy in cerebral metastases from malignant melanoma fotemustine therefore warrants further study.
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PMID:Phase II trial of fotemustine in patients with metastatic malignant melanoma. 789 45

Taxol (paclitaxel, Bristol-Myers Squibb Company, Princeton, NJ), a drug extracted from the stem bark of the western yew, shows great promise as an antineoplastic agent for ovarian, breast, nonsmall cell lung, and head and neck cancers; melanoma; and leukemia. Although Taxol first was isolated in 1971, completion of many phase I studies was delayed until 1988, primarily because the drug caused severe hypersensitivity reactions. Other side effects of Taxol include cardiotoxicity, nausea and vomiting, diarrhea, mucositis, myelosuppression, tingling and numbness of the hands and feet, myalgia and arthralgia, alopecia, fatigue, headache, irritation at the injection site, and taste changes. Nursing care includes measures for preventing or minimizing side effects, close assessment and monitoring of potential side effects, patient education, and support. Because of the environmental impact of harvesting the western yew for Taxol, semisynthetic preparations such as taxotere are being explored.
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PMID:Taxol: a promising new drug of the '90s. 790 60

Nausea and vomiting develop during surgery, radio- and/or chemotherapy of malignant diseases. Several drugs belonging to different groups of compounds have been used against them in a large scale. After listing these drugs the authors explained their results. Between January 1992 and 1993, 40 chemotherapy-native melanoma patients were treated by emetogen chemotherapy. The incidence, the time-relationship and the number of nausea and vomiting were investigated during the first chemotherapy course. In the second part of the study ondansetron was applied to 50 patients having developed nausea and vomiting in earlier chemotherapy. When using metoclopramide and corticosteroid during the chemotherapy nausea and vomiting developed in 9 (22.5%) and 20 (50%) cases. Nausea 8/50 (11.25%) was observed with the application of Zofran p. o. while vomiting did not develop. Delayed emesis has not been seen during the antiemetic therapies. The laboratory parameters were within the normal range.
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PMID:[Nausea and vomiting in cytostatic therapy of melanoma patients with the use of metoclopramide and corticosteroid or ondansetron]. 797 Jun 61

Isolated limb perfusion (ILP) with melphalan is an effective treatment for recurrent melanoma, but complete remission is achieved only in about 40% of patients. Regional toxicity is common, causing short-term disability and occasional longterm incapacity. Methods to maximize the efficacy and minimize the toxicity were investigated in 210 ILPs undertaken at the Sydney Melanoma Unit. Toxicity was found to be related to peak melphalan concentration, as well as to the area under the curve and maximum temperature. A dye dilution technique has been developed to measure perfusion circuit volume, so that a drug dose can be given to achieve an appropriate concentration. ILP with cisplatin was less effective and produced greater toxicity than ILP with melphalan; other drugs and drug combinations warrant investigation. Prophylactic ondansetron successfully controlled post-operative nausea and vomiting in most patients. Daily measurement of serum creatine phosphokinase (CPK) allowed early recognition of impending severe toxicity, with the greatest risk if CPK exceeded 1000 IU/l after the first post-perfusion day. Isolated limb 'infusion' (ILI) with melphalan, using percutaneously inserted catheters, is a much simpler procedure than ILP and has been found to be effective and easily repeated. The morbidity of ILP and ILI may be minimized by excluding the foot or hand with a rubber bandage.
Melanoma Res 1994 Mar
PMID:Maximizing efficacy and minimizing toxicity in isolated limb perfusion for melanoma. 803 96

Didemnin B is a cyclic peptide isolated from the marine tunicate Trididemnin cyanophorum. It is a known potent inhibitor of RNA, DNA and protein synthesis, with activity against the murine B16 melanoma. Fourteen patients with disseminated malignant melanoma were evaluated in a Southwest Oncology Group phase II trial of didemnin B at 4.2 mg/m2 by 30 min i.v. infusion every 28 days (SWOG-8754). Only patients with no prior chemotherapy were eligible; prior radiation therapy, surgery and at most one prior biologic regimen were allowed. Patients with brain metastasis were eligible only if the disease in the brain had been treated and controlled. All patients had to have normal renal and hepatic function and adequate granulocyte and platelet counts, a performance status of 0-2, and bidimensionally measurable disease. Fourteen patients were entered on the study; five received one and nine received two courses of didemnin B. No responses were noted among the 11 patients evaluable for response. Five patients developed unusual but reversible hypersensitivity reactions during the second course of therapy. Other toxicity in this trial was nausea and vomiting and diarrhea, none of severity greater than grade 3. Given the lack of antitumor efficacy and the unusual toxicity, further evaluation of didemnin B in this dose and schedule in malignant melanoma is not warranted.
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PMID:Didemnin B in metastatic malignant melanoma: a phase II trial of the Southwest Oncology Group. 804 97

Amonafide (AMF), NSC 308847 is an investigational anticancer drug acting as a DNA intercalating agent. This paper presents results of a phase II clinical study of AMF in disseminated malignant melanoma. Twenty patients, eleven males and nine females, with biopsy proven malignant melanoma, performance status 0-2; median age 59 (range 29-74), and no previous chemotherapy, were treated with AMF 300 mg/m2/day by 60 min i.v. infusion for five days repeated every three weeks. Fifteen patients had lung (9 patients) and/or liver (8 patients) involvement. None had known brain metastasis at entry. All 20 patients were evaluated for response and toxicity. Six patients had stable disease and fourteen had increasing disease. With 0/20 responses, the upper 95% confidence limit for the response rate was 14%. The median survival time was 5.7 months. Hematologic toxicity was dose limiting with the incidence of leucopenia 45% and thrombocytopenia 20%. The nonhematologic toxicities included nausea and vomiting (60%), alopecia (20%), headaches (15%), diarrhea (10%), and phlebitis (10%). We conclude that AMF administered at this dose and schedule is not active in the treatment of patients with malignant melanoma, previously untreated with chemotherapy.
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PMID:Evaluation of amonafide in disseminated malignant melanoma. A Southwest Oncology Group study. 826 36

In a multi-centre randomised clinical trial comparing dacarbazine (DTIC) plus recombinant interferon-alfa2a (IFN) versus DTIC alone for patients with metastatic malignant melanoma, aspects of quality of life (QL) were measured prospectively by patients using linear analogue self assessment (LASA) scales including the GLQ-8 and by doctors using Spitzer's QL Index. QL scores and performance status at the time of randomisation were available for 152 of 170 eligible patients. These scores carried significant prognostic information. In univariate analyses, Spitzer QL Index assessed by the doctor and LASA scores for physical wellbeing (PWB), mood, pain, appetite, nausea and vomiting, GLQ-8 total and overall QL were significant (P < 0.01) predictors of subsequent survival. QL Index and LASA scales for mood, appetite, and overall QL remained independently significant (all P < 0.05) in multivariate models allowing for significant prognostic factors other than QL (liver metastases and performance status). These findings closely parallel those in patients with metastatic breast cancer. They add further validity to the QL Index and LASA scores, provide the first evidence of the prognostic significance of the GLQ-8, and argue strongly for the routine assessment of QL in future therapy trials.
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PMID:Prognostic value of quality of life scores in a trial of chemotherapy with or without interferon in patients with metastatic malignant melanoma. 839 88

Decarbazine is an imidazole dimethyltriazene with reproducible activity in patients with metastatic melanoma. CB10-277 is a phenyl dimethyltriazene which, like dacarbazine, requires metabolic activation to its corresponding monomethyl species for antitumour activity. In preclinical models (human melanoma xenografts and transplantable rodent tumours) CB10-277 showed a similar spectrum and level of activity when compared to dacarbazine. Pharmacokinetic studies were performed with CB10-277 in mice treated i.v. at the LD10 (750 mg m-2) and plasma analysed by HPLC. The parent drug area under the plasma concentration vs time curve (AUC) was 142 mM x minutes. Drug metabolism occurred as evidenced by the HPLC identification of the monomethyl species (AUC = 8 mM x minutes) as well as other metabolites. A Phase I trial using a short infusion with doses repeated every 21 days has been performed. Thirty-six patients received 80 courses over a dose range of 80-6,000 mg m-2. The dose limiting toxicity was nausea and vomiting which occurred in 80% of the evaluable courses > or = 900 mg m-2. The only other common side effect was a flushing or warm sensation, which occurred in over 75% of courses at > or = 1,350 mg m-2. There were no hemodynamic consequences. Responses occurred in patients with melanoma (one complete, two partial, one mixed/11), sarcoma (one mixed/6) and carcinoid (one partial/l). Pharmacokinetics were performed in 46 courses. The CB10-277 AUC increased linearly with dose (r = 0.9203, P < 0.001) up to 700 mM x minutes at 6,000 mg m-2). Evidence of CB10-277 metabolism was observed, as in mice, by detection of the monomethyl species and other metabolites. However, the plasma levels of the monomethyl species in patients (1.8 and 3.7 mM x minutes at 6,000 mg m-2) were less than those predicted from studies in mice. Despite this, antitumour activity in dacarbazine sensitive histologies was observed and additional studies with CB10-277 are recommended.
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PMID:Preclinical, phase I and pharmacokinetic studies with the dimethyl phenyltriazene CB10-277. 843 67

In this double-blind, randomized trial performed at five study centers, the prophylactic, antiemetic effect of two different dosages of tropisetron (Navoban; Sandoz Pharma Ltd, Basel, Switzerland) was investigated in dacarbazine-treated patients with melanoma. Patients received tropisetron 5 mg or 10 mg orally (as one capsule) once daily (minimum 3 days) on each day of chemotherapy. No significant differences were found in the effects of tropisetron 5 mg and 10 mg. During the first 24 hours, total control of vomiting was seen in 93% and 98% of patients receiving tropisetron 5 mg and 10 mg, respectively. Total control of nausea was achieved in 84% and 80% of patients receiving tropisetron at these dosages. Over days 2 to 7 of chemotherapy, total control of vomiting and nausea remained high. Patients reported that quality of life remained good throughout chemotherapy, as did mood; only a small decrease in food intake occurred. Tropisetron was well tolerated. Constipation was the most common adverse event, occurring in 13% of patients. Headache (4%), diarrhea (4%), and anorexia (2%) also were observed.
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PMID:Dose comparison of tropisetron (Navoban) 5 mg and 10 mg orally in the prophylaxis of dacarbazine-induced nausea and emesis. 911 21

This paper presents the case of a female patient with liver metastases of a malignant melanoma showing complete remission after 10 courses of regional, intra-arterial chemotherapy with cisplatin. The drug was administered as continuous infusion for 5 days. The daily dosage amounted to 30 mg/m2. The interval between courses was 6 weeks. Nausea and vomiting were seen after each course, while pathological serum creatinine levels only appeared after the eighth course. The only lesion in the liver still visible on CT scan after chemotherapy was removed by left hemihepatectomy. Meticulous histological examination revealed a big focus of necrotic tissue without any tumour cells. At the time of publication the patient is alive and disease-free over 9 years later.
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PMID:Long-term complete remission of melanoma liver metastases after intermittent intra-arterial cisplatin chemotherapy and surgery. 923 5


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