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)

A total of 38 patients with metastatic melanoma received monthly chemotherapy with cisplatin at a dose of 200 mg/m2, per cycle; 14 received 20 mg/m2 cisplatin i.v. on days 1-5 and 24 were given 100 mg/m2 i.v. on days 1 and 8. Objective responses were seen in 2/14 treated on days 1-5 and in 5 of 22 evaluable subjects receiving cisplatin on days 1 and 8, for an overall response rate of 22%. The median survival of all patients was 6 months, with no significant difference observed between the two schedules. Severe neurotoxicity and myelosuppression were more common in patients treated on days 1-5. Two patients treated in this manner were bedridden due to neurotoxicity and four developed grade 4 leukopenia after the first cycle of chemotherapy. Only one patient treated with the divided-dose schedule became leukopenic during the first cycle, and none of the patients were debilitated by neurotoxicity. Thrombocytopenia was statistically more severe. Nausea and vomiting, fatigue, ototoxicity, and paresthesia were seen with equal frequency. Very high doses of cisplatin can be delivered with acceptable toxicity using a divided-dose schedule. As the response rate on this schedule appeared to be comparable with that achieved on the more toxic consecutive 5-day schedule, the former deserves to be tested in diseases known to show a dose response to cisplatin. However, in melanoma, administration of 200 mg/m2 per course did not appear to be associated with a markedly improved response rate, compared with cisplatin alone at "standard" doses.
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PMID:High-dose cisplatin in disseminated melanoma: a comparison of two schedules. 230 98

We evaluated the immediate and long-term effects on psychological distress and coping methods of a 6-week, structured, psychiatric group intervention for postsurgical patients with malignant melanoma. The intervention consisted of health education, enhancement of problem-solving skills, stress management (eg, relaxation techniques), and psychological support. In spite of good prognosis, most patients had high levels of psychological distress at baseline, comparable with other patients with cancer. However, at the end of brief psychiatric intervention, the experimental subjects (n = 38), while not without some distress, exhibited higher vigor and greater use of active-behavioral coping than the controls (n = 28). At 6 months' follow-up, the group differences were even more pronounced. The intervention-group patients then showed significantly lower depression, fatigue, confusion, and total mood disturbance as well as higher vigor. They were also using significantly more active-behavioral and active-cognitive coping than the controls. These results indicate that a short-term psychiatric group intervention for patients with malignant melanoma effectively reduces psychological distress and enhances longer-term effective coping.
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PMID:A structured psychiatric intervention for cancer patients. I. Changes over time in methods of coping and affective disturbance. 237 43

Preclinical data suggest synergy of interleukin-2 (IL-2) combined with alpha-interferon (IFN). In addition, toxicities of IL-2 may be decreased by intermittent continuous infusion. The purpose of this trial was to determine the maximum tolerated dose (MTD) of recombinant IL-2 combined with alpha-IFN in patients with renal cancer, colon cancer, melanoma, and malignant B-cell disease. IL-2 was given by continuous i.v. infusion at an initial dose of 5 X 10(5) units (U)/m2/d for 4 days plus IFN at 6 X 10(6) U/m2/d intramuscularly days 1 and 4 weekly for 4 weeks. Patients who achieved a response or stable disease received an additional 4 weeks of therapy. IL-2 doses were increased to 1, 2, 3, 5, and 7 X 10(6) U/m2/d with three to eight patients at each dose level, at each of the two participating institutions. The dose of IFN was 6 X 10(6) U/m2 days 1 and 4 for all but five patients whose IFN dose was doubled to 12 X 10(6) U/m2/d. Forty-three patients were entered on this study with 34 completing at least 4 weeks of therapy. Six patients were taken off study because of Grades III or IV pulmonary, neurologic, or cardiac toxicity; one for progressive disease; one for CNS metastases, and one for personal reasons. All of the toxicities were reversible. Chills and fever were universal, especially on days 1 and 4. Mild and moderate nausea, vomiting, diarrhea, anorexia, malaise, and cutaneous erythema were present in most patients. Fluid retention and occasional pleural effusions were observed at the higher IL-2 doses but were not dose-limiting. Significant hypotension associated with oliguria was seen, and these patients were treated with vasopressors and colloids. None of the patients required ICU admission. Thirty-four patients were evaluable for response. There were 4/18 (22%) renal cell patients who experienced a partial response. No responses were seen in patients with melanoma, lymphoma, or colorectal cancer. The combined debilitating symptoms of fatigue, diarrhea, hypotension, fluid retention, and anorexia defined the MTD as 5 X 10(6) U/m2/d of IL-2 and 6 X 10(6) U/m2 of alpha-IFN.
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PMID:A phase I study of recombinant human interleukin-2 and alpha-interferon-2a in patients with renal cell cancer, colorectal cancer, and malignant melanoma. 238 96

Sixteen patients with metastatic malignant melanoma were treated with poly(I,C)-LC 5 mg/m2 twice weekly by intravenous injection. No antitumor responses occurred. Fever (frequently greater than 40 degrees C) and fatigue were dose limiting toxicities. One patient developed a fever of 42.2 degrees C when poly(I,C)-LC was given on 2 consecutive days. Interferon was consistently detected in the serum 8 h after a single injection of poly(I,C)-LC (median titer 199 U/ml). No enhancement of interferon induction was detected on the second day when poly(I,C)-LC was given on 2 consecutive days.
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PMID:An Eastern Cooperative Oncology Group phase I-II pilot study of polyriboinosinic-polyribocytidylic acid poly-L-lysine complex in patients with metastatic malignant melanoma. 241 64

A patient with isolated cecal metastasis of malignant melanoma whose symptoms of fatigue, exertional dyspnea, and an abdominal mass were relieved by operation is reported. Palliative resection appears to offer significant benefit in patients with symptomatic melanoma involving the colon, particularly if the lesion is solitary.
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PMID:Metastatic melanoma involving the colon. Report of a case. 1073 31

Many drugs are applied in local treatment for skin malignant tumors. These drugs are living-BCG, OK-432, MY-1, WPG, interferon preparation (alpha, beta and gamma), TNF, IL-2, peplomycin, bleomycin and others. Some of them already have completed clinical trials and others are under clinical observation. In local administration of these drugs, skin lesions (malignant melanoma, CTL-mainly mycosis fungoides, carcinoma in situ and others) show good improvement. The effects were more observed in the tumors with diameters of 1 cm or less and appeared 3 to 10 injections in most cases. As complications, there are fever, general fatigue, vomiting, anorexia, leucopenia and others. Among them, the fever was most observed immediately after injections without any more severe complications. It may be concluded that treatment by intratumoral administration is useful for skin malignant tumors.
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PMID:[Clinical effects induced by intratumoral administration of anti-cancerous drugs in skin malignant tumors]. 246 39

The effects and toxicities of interferon alfa are described, and the role of the pharmacist in making decisions and providing education about biologic response modifiers (BRMs) is discussed. Interferons have both direct antitumor activity and extensive effects on the immune system. Two recombinant interferon alfa products--interferon alfa-2a and interferon alfa-2b are available commercially. Indications in FDA-approved labeling for interferon alfa include the treatment of hairy-cell leukemia, acquired immunodeficiency syndrome-related Kaposi's sarcoma, and genital warts; however, it also is being used successfully against early chronic myelogenous leukemia, low-grade non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, and previously untreated multiple myeloma. Other malignancies that respond to treatment with interferon alfa are malignant melanoma, ovarian carcinoma, and renal cell carcinoma. The toxic pattern of interferon alfa consists of flu-like symptoms, which are seen at all doses, on all schedules, and in virtually all patients. After repeated dosing, the chronic toxicities of anorexia, weight loss, and malaise and fatigue may develop. Myelosuppression, central nervous system toxicity, increased hepatic enzyme concentrations, nausea and vomiting, and cardiovascular toxicity also are possible. Serum neutralizing antibodies may be formed during therapy; this phenomenon may affect the clinical outcome. Numerous BRMs are being investigated for clinical use, and pharmacists must become conversant in the issues that surround these agents. Areas in which pharmacist involvement and knowledge are important include overall cost, product similarities and differences, dosing and scheduling, drug delivery systems, ways to minimize waste, adverse effects and their management, drug interactions, storage requirements, differences in production and purification techniques among manufacturers, and education of patients and staff.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biologic response modifiers: the interferon alfa experience. 248 96

Sixty-six patients with disseminated malignancy were treated with recombinant interleukin-2 (IL-2) on a three times a week (M, W, F) IV-bolus injection schedule. Doses ranged from 0.001 to 14.0 x 10(6) units/M2 body surface area. Consecutive groups of 3-5 patients were placed on each dose level and were maintained on that level except for dosage de-escalation for toxicity. Toxicity to all major organ systems were noted with major toxicity including fever and chills, anorexia, fatigue and malaise, arthralgias and arthritis as well as hepatic and renal toxicity. All toxicity reversed within one week of drug cessation. Renal toxicity manifested by azotemia, arthritis and fatigue were the common dose limiting toxicities and the maximally tolerated dose was 12 x 10(6) units/M2. Pharmacokinetic studies indicated a short half-life (T1/2 alpha = 7-23 minutes). At doses over 0.5 x 10(6) units/M2 increases in absolute lymphocytes and eosinophil counts were noted. All T lymphocyte subsets increased. Maximal increases were seen at 4-8 x 10(6) units/M2 with a lesser increase at 10-14 x 10(6) units/M2 dosage level. Circulating NK cells also increased while circulating LAK cells were detected during therapy. Partial responses were noted in 3 patients with melanoma. These lasted 4, 6 and 16 months and involved pulmonary, pulmonary plus mesenteric and retro-orbital plus hepatic metastases respectively in these patients.
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PMID:Phase I study of cancer therapy with recombinant interleukin-2 administered by intravenous bolus injection. 264 25

alpha-Interferon has antitumor activity in a variety of malignancies but is frequently associated with unacceptable toxic side-effects. The routine use of agents potentially capable of reducing these side-effects has not been recommended out of concern for possible reductions in the therapeutic activity of interferon. We conducted a prospective randomized trial of alpha-interferon given with or without indomethacin to patients with malignant melanoma to determine what effect, if any, indomethacin might have on the toxic, immunomodulatory, and therapeutic properties of interferon in this disease. 53 patients were stratified according to performance status and randomized to receive alpha 2b-interferon, 20 million units per m2 i.v., 5 days per week for 4 weeks followed by 10 million units per m2 s.c. three times per week, either with or without indomethacin, 25 mg orally three times a day. The overall major response rate was 13% (three complete responders and three partial responders among 47 evaluable patients) and was the same on both arms. The mean maximal temperature elevation induced by interferon was significantly reduced (from 102.1 to 100.7, P = 0.0002) by indomethacin, but the incidence and severity of interferon-related fatigue, reduction in performance status, headache, depression, confusion, elevations in liver function tests, and myelosuppression were no different in either arm of the study. Indomethacin did not reduce the frequency of dose reductions for toxic side-effects and did not permit the administration of higher interferon doses. Peripheral blood natural killer activity was significantly enhanced in patients during maintenance therapy whether or not they received indomethacin. Indomethacin appeared to inhibit augmentation of natural killer activity during high dose induction therapy. Immunological changes did not correlate with response status. We conclude that indomethacin can reduce the fever associated with interferon therapy in patients with malignant melanoma without interfering with its therapeutic or chronic immunomodulatory activities. Since fever is rarely the dose-limiting toxicity of interferon, indomethacin is of marginal benefit to patients with malignant melanoma receiving interferon at the doses outlined in this study.
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PMID:Randomized trial of recombinant alpha 2b-interferon with or without indomethacin in patients with metastatic malignant melanoma. 264 94

Twenty-five patients with disseminated cancer (nine with renal cell carcinoma, five with melanoma, three with Hodgkin's lymphoma and chronic myelocytic leukemia [CML], two with soft tissue sarcoma, one each with large-cell lymphoma, breast cancer, and colon cancer), 13 males and 12 females, aged 25 to 68, were treated with recombinant human interleukin-2 (rIL2) by continuous infusion and adoptive transfer of autologous lymphocytes activated in vitro with IL2. Patients underwent leukapheresis on days 1, 8, 15, and 22 of the treatment. Cells, bulk activated for 20 hours in serum-free culture medium with 1,000 U IL2/mL in transfusion transfer packs as culture vessels, were transfused the following day. The infusion of IL2 by continuous infusion for six days started immediately after each adoptive transfer for 4 weekly courses. The dose of IL2 was escalated weekly in each patient; starting doses of IL2 were also escalated in subsequent cohorts of patients until maximally tolerated doses were reached. Nine patients had objective tumor regressions (three with renal cell cancer, two with Hodgkin's lymphoma, and one each with melanoma, sarcoma, breast, and colon cancer). Six responses were partial, two were minor, and one was mixed. Responding patients were maintained with IL2 by continuous infusion for six days every 6 to 8 weeks, without adoptive cell transfer. The median duration of responses was 16 weeks (3 to 60 + weeks). Tumor regression was related to the dose of IL2 (greater than or equal to 3.4 x 10(6) U/m2/d for six days) and to the in vivo lymphoproliferative effects of the lymphokine, but not to the total number of cells adoptively transferred. Side effects of treatment were transient and quickly reversible. Renal, hepatic dysfunction, and dyspnea were directly related to the dose of IL2 and to lymphocytosis. Other toxicities were mild hypotension with mild fluid retention, oral mucositis, anemia, thrombocytopenia, fever, and fatigue.
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PMID:Recombinant interleukin-2 by continuous infusion and adoptive transfer of recombinant interleukin-2-activated cells in patients with advanced cancer. 266 33


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