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)

Both interferon-alpha (IFN-alpha) and alpha-difluoromethylornithine (DFMO) have shown modest activity as single-agent therapy in the treatment of malignant melanoma. Several investigators have demonstrated true synergism in vitro of the combination of DFMO and IFN-alpha against human tumor cells, including melanoma. We have investigated this combination in 17 patients with malignant melanoma in a Phase I trial. Patients were treated with 4 or 6 g/m2/day of oral DFMO in 3 divided doses for 11 days, followed by a 3-day rest period. Concomitant administration of 1.5, 3.0, 6.0 or 9.0 x 10(6) U/m2 IFN-alpha intramuscularly was given. The maximum tolerated dose was 4 g/m2/day of DFMO plus 6 x 10(6) U/m2/day of IFN-alpha. Dose-limiting toxicity occurred in 3 of 3 patients receiving 9 x 10(6) U/m2 IFN-alpha and consisted of leukopenia, fatigue, and weight loss. Other toxicities were mild and included reversible hearing loss, diarrhea, nausea, and vomiting. Three responses were seen, including one partial response (PR) of soft tissue metastases, one PR of lung and liver, and one complete response of liver metastases without clearance of carcinomatous meningitis. A Phase II trial has been initiated based on these encouraging results.
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PMID:A phase I trial of recombinant interferon-alpha and alpha-difluoromethylornithine in metastatic melanoma. 313 43

24 patients with advanced, histologically proven cancer were treated with difluoromethylornithine 2.25 g/m2 orally every 6 h for the first 7 days of each 4-week treatment cycle. These patients also received daily i.m. doses of recombinant human alpha 2a-interferon (IFN) on Days 3 through 7 of each cycle. IFN doses of 3, 6, 12, 24, 36, and 48 X 10(6) units/m2 have been studied utilizing three patients at each daily dose level. Three additional patients have been observed at each of the two highest doses for better toxicity definition. This combination produced slight transient declines in leukocyte and platelet counts and transient rises in serum aspartate aminotransferase; however, these changes were no more pronounced at the higher IFN doses than at daily doses of 6 X 10(6) units/m2. Mild nausea and vomiting occurred in most patients and mild diarrhea also was common at all IFN dose levels. Chills, fever, myalgia, lethargy and fatigue, and anorexia were also observed at all IFN doses; however, lethargy and fatigue (lassitude) seemed to be the major factor which limited patient tolerance of IFN to 48 X 10(6) units/m2 daily. No ototoxicity was identified clinically or audiometrically and no life-threatening toxicity has occurred. Initial Phase II studies in melanoma are currently in progress.
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PMID:Phase I study of difluoromethylornithine in combination with recombinant alpha 2a-interferon. 314 Oct 46

Based upon the in vitro synergistic activity of interferon-beta (IFN-beta) and interferon-gamma (IFN-gamma) observed in melanoma cells, we initiated a Phase II trial using the combination to determine the clinical antitumor efficacy in patients with advanced disease. Fifteen patients with metastatic malignant melanoma were given 2,000 micrograms of recombinant IFN-gamma (rIFN-gamma) (Biogen) intravenously (i.v.) over 10 min, followed by a 10 min i.v. injection of 30 million units of recombinant IFN-beta (rIFN-beta ser) (Triton) 3 x/week. Six patients had skin, soft tissue, nodal, or subcutaneous metastases, 6 had visceral disease only, and 3 had both. Seven patients had received prior treatment, including chemotherapy (6), radiotherapy (3), and/or immunotherapy (3). Side effects included typical IFN constitutional symptoms such as anorexia, fatigue, nausea, and myalgias, but were not dose limiting. The mean drop in the white blood cell count (WBC) following 1 month of therapy, compared to baseline, was 3.3 x 10(3)/mm2 (p = 0.002); the mean increase in SGOT was 24.1 U/l (p less than 0.001). One patient had a dose reduction for Grade III anorexia and fatigue which did not resolve with repeated treatment. One patient with liver metastases had radiographical and clinical stabilization of his disease for 1 year. No responses were seen. The median time to progression was 6 weeks. Two patients' tumors were evaluable in the human tumor colony forming assay (HTCFA) and were markedly sensitive to the antiproliferative effects of IFN combinations. Both patients, however, failed to respond clinically.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase II trial of a combination of interferon-beta ser and interferon-gamma in patients with advanced malignant melanoma. 314 69

Thirteen patients with metastatic melanoma and ten patients with advanced renal cell cancer (RCC) received interferon alfa-2a (Roferon-A) and vinblastine. In melanoma the interferon dose was 3-9 million IU i.m., escalated daily for 10 weeks, and in RCC the dose was 18 million IU three times a week i.m. The dose of vinblastine was 0.075-0.15 mg/kg every third week i.v. One of the ten evaluable patients with melanoma had partial remission (PR; 11%) and three presented no change (NC). Three of seven evaluable patients with renal cell carcinoma had PR (43%) and three NC. Duration of the remission was 10 months in the melanoma patients and 7+, 10+, and 7+ in the RCC patients. The three times a week schedule was better tolerated. The most common side effects were fever, fatigue, loss of taste, weight loss, and neutropenia. On the basis of these results it can be concluded that in melanoma the combination of daily administration of interferon and vinblastine is not effective, whereas in renal cell cancer interferon and vinblastine treatment given three times a week seems to be favorable.
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PMID:Combined interferon and vinblastine treatment of advanced melanoma and renal cell cancer. 318 Jan 44

From 1977 to 1982, 62 patients with various advanced malignant solid tumors were treated by HD-MTX-CFR therapy and totally 129 courses were given. Majority of the patients suffered from malignant lymphoma (10), osteogenic sarcoma (11), lung cancer (16), esophageal cancer (3), breast cancer (3) and malignant melanoma (4). All were confirmed by cytology or pathology except one primary liver cancer. There were clinically measurable lesions in 59 patients for evaluation of the treatment, and 3 osteogenic sarcoma patients without metastasis were given a postoperative adjuvant chemotherapy. 33 out of 62 had received chemotherapy and/or radiotherapy before. Dose of MTX ranged from 2 to 3 gm per course in most patients and dose of CF, from 9 to 12 mg every 6 hours for 3 days. 2 (3.4%) patients achieved complete remission (1 osteogenic sarcoma and 1 malignant lymphoma) and 8 (13.6%), partial remission (1 osteogenic sarcoma, 5 malignant lymphoma, 1 esophageal cancer and 1 breast cancer) with a total response rate of 15.9%. No response was observed in all 16 lung cancers. The main side effects of HD-MTX-CFR therapy were leukopenia, thrombocytopenia, elevation of SGPT, nausea, vomiting, mucositis, skin rash, fever and fatigue. All patients were followed more than 3 years. 4 patients are still alive (9, 9, 4 and 7 years, respectively), including 3 osteogenic sarcoma patients who received postoperative adjuvant chemotherapy and 1 mycosis fungoides.
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PMID:[High-dose methotrexate with citrovorum factor rescue (HD-MTX-CFR) in the treatment of malignant solid tumors--clinical analysis of 62 patients]. 326 85

The combination of Interferon and low-dose cyclophosphamide synergistically inhibits the growth of human breast cancer xenografts, explanted human non-small cell lung carcinoma, and other experimental tumors. To determine whether this combination would demonstrate clinical efficacy against refractory solid tumors, we used recombinant alpha-2b-Interferon, 10 MU/m2 subcutaneously three times per week, and cyclophosphamide, 25 mg orally twice daily, in 42 patients (25 renal cell carcinoma, 17 melanoma). Two patients were inevaluable due to premature removal from the study. The toxicity profile did not differ substantially from that of Interferon alone with malaise, fatigue, fevers, and chills predominating. Sixteen percent of patients experienced an alteration in mental status. Of 40 patients evaluable for response, there were two partial responders (one renal cell carcinoma, one melanoma) and four minor responders (all renal cell carcinoma). The responder with melanoma had previously failed therapy with dacarbazine (DTIC). Seventeen patients remained stable for a median follow-up of 6 months. We conclude that this regimen is well tolerated; however, the combination of Interferon and low-dose cyclophosphamide used in this way does not appear to be superior to the same dose and schedule of Interferon used alone.
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PMID:Phase II trial of recombinant alpha-2b-interferon and low-dose cyclophosphamide in advanced melanoma and renal cell carcinoma. 327 75

We conducted a trial of a murine monoclonal antimelanoma antibody-ricin A chain immunotoxin (XOMAZYME-MEL) in 22 patients with metastatic malignant melanoma. The dose of immunotoxin administered ranged from 0.01 mg/kg daily for 5 days to 1 mg/kg daily for 4 days (total dose: 3.2 to 300 mg). Side effects observed in most patients were a transient fall in serum albumin with an associated fall in serum protein, weight gain, and fluid shifts resulting in edema. In addition, patients experienced mild to moderate malaise, fatigue, myalgia, decrease in appetite, and fevers. There was a transient decrease in voltage on electrocardiograms without clinical symptoms, change in serial echocardiograms or elevation of creatine phosphokinase MB isozyme levels. Symptoms consistent with mild allergic reactions were observed in three patients. The side effects were related to the dose of immunotoxin administered and were generally transient and reversible. Encouraging clinical results were observed, even after a single course of a low dose of immunotoxin. In addition, localization of antibody and A chain to sites of metastatic disease was demonstrated by immunoperoxidase staining of biopsy specimens. Additional studies are being conducted to continue the evaluation of safety and efficacy of immunotoxin therapy for malignancy.
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PMID:Therapy of patients with malignant melanoma using a monoclonal antimelanoma antibody-ricin A chain immunotoxin. 349 66

A total of 21 patients with advanced metastatic malignant melanoma were treated in this efficacy study of recombinant leukocyte A interferon (interferon alpha-2a). Patients received 18 X 10(6) units interferon alpha-2a by i.m. injection daily for the first 10 weeks and then three times weekly for a further 4 months. The symptoms of toxicity observed in this study resembled those previously reported for alpha interferons and included fever, chills, fatigue, anorexia, myalgia, headache, occasional nausea and vomiting, dose-dependent reversible leukopenia, and hepatic transaminase elevations. Of the 21 patients, 12 had evidence of tumor progression, 6 had stable disease for at least 2 months, and complete remission was seen in 3 patients with stage III melanoma. We conclude that interferon alpha-2a appears to have some antiproliferative effect in metastatic malignant melanoma. While its use in stage IV patients with big tumor masses is doubtful, there seems to be therapeutic benefit in earlier stages.
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PMID:Phase II trial of recombinant leukocyte A interferon in advanced malignant melanoma. 358 16

Betaseron (beta ser17-interferon) was administered to 19 patients (17 evaluable) with advanced melanoma by two schedules. Patients received either 30 X 10(6) units (mU) by intravenous bolus 5 days a week for 2 weeks followed by 2 weeks rest, or 30 mU daily for 5 days in week 1, 60 mU daily for 5 days in week 2, then twice-weekly doses escalating from 90 to 270 mU. Toxicity commonly included malaise, fatigue, fever, and weight loss. Mild hematologic, gastrointestinal, and hepatic toxicity were also seen, as well as an episode of atrial fibrillation in a patient with mitral valvular disease. No responses to therapy occurred.
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PMID:Phase II study of betaseron (beta ser17-interferon) as treatment of advanced malignant melanoma. 362 29

Based on the reports of activity of interferons against metastatic melanomas, we conducted a phase II study of recombinant interferon alfa-2a (Roferon-A, Hoffmann-La Roche, Nutley, NJ) in 66 patients with disseminated melanoma. All patients had excellent Eastern Cooperative Oncology Group (ECOG) performance status (0 to 1), and no evidence of brain metastases. Thirty patients had previously received chemotherapy and the remainder were untreated. The first 35 patients were treated on a daily schedule starting with a Roferon-A dose of 3 X 10(6) U/d and escalating to a maximum of 36 X 10(6) U/d over a period of 12 days. Because of excessive toxicity, the second group of 31 patients were treated on a fixed dose of 18 X 10(6) U/d [corrected] three times weekly (TIW). Among the 62 evaluable patients, five achieved an objective response for a response rate of 8% (95% confidence limits, 3% to 18%). Four patients had minor regressions and eight patients had stability of disease. The responses were evenly distributed between the two dose schedules. The major toxicity of interferon consisted of a constitutional syndrome of anorexia, fever, weight loss, and fatigue, which required a dose reduction in 75% of the patients on the daily schedule. Our data revealed a modest level of activity, which was not influenced by prior treatment or by the dose or schedule of interferon. Because of substantial toxicity with the daily schedule, we recommend a dose of 18 X 10(6) U/d [corrected] if interferon is used in the treatment of patients with melanoma.
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PMID:Clinical evaluation of recombinant interferon alfa-2a (Roferon-A) in metastatic melanoma using two different schedules . 362 46


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