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 role of combination chemotherapy in the treatment of advanced non-small-cell lung cancer is controversial. At best, a small survival benefit can be achieved. Therefore, other treatment modalities are needed. On the basis of the promising treatment results with interleukin-2 (IL-2) -containing immunotherapy in renal cell cancer and melanoma, we performed a phase I-II study with IL-2 and interferon alpha (IFN-alpha). Eligible patients were treated with IL-2 18 x 10(6) IU/m2/day by continuous intravenous infusion (c.i.v.) for 3 days. On the same days, 5 x 10(6) U/m2/day IFN-alpha was given intramuscularly. After a rest period of 4 days, patients at the first dose level received IL-2 2.4 x 10(6) IU/m2/day c.i.v. for a period of 28 days, followed by 14 days' rest, 14 days' treatment, 7 days' rest, and a final treatment for 14 days. Patients at the second dose level were treated according to the same schedule, in which the dose of IL-2 was increased to 3.6 x 10(6) IU/m2/day. During low-dose IL-2 treatment, patients received IFN-alpha 5 x 10(6) U/m2/day on days 1 and 4 of each week. Eleven patients were admitted to the study, six at the first and five at the second dose level. Median age was 54 years; all patients had a performance status of 0 or 1. The most important adverse effects included anorexia, fatigue, nausea, and headache, which were not dose limiting. In the 11 patients treated, no responses were seen. Nine patients developed progressive disease during the first 5 weeks of treatment. We concluded that this regimen of IL-2 and IFN-alpha is ineffective.
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PMID:Interleukin-2 and interferon-alpha in the treatment of patients with advanced non-small-cell lung cancer. 132 67

A 46-year-old woman presented with abdominal pain, nausea vomiting and abdominal distention. Small bowel x-rays and CT scan of the abdomen revealed small bowel obstruction due to malignant melanoma. The diagnosis of cutaneous melanoma was performed 8 years prior to admission on one lesion in the back. Patient received surgical treatment. Completed resection of an involved jejunal [correction of ileal] segment was performed. Three tumor masses were found at laparotomy. Metastasis from malignant melanoma at the gastrointestinal tract occurs frequently though rarely are these intestinal lesions symptomatic. The efficacy of surgical treatment for symptomatic metastatic melanoma is justified to relief symptoms and prolonged survival.
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PMID:[Symptomatic malignant melanoma of the small intestine]. 134 Nov 16

19 patients with advanced malignant melanoma were treated with fotemustine and dacarbazine. Data recorded and available for evaluation in all patients included clinical and histopathological parameters of the primary melanoma, blood chemistry, blood cell count, chest X-ray, ultrasound and bone scan for initial staging of the site of metastases and follow-up during treatment. Dosage was fotemustine 100 mg/m2 and dacarbazine 200 mg/m2 intravenously twice monthly on days 1 and 8, repeated for a maximum of six courses. There were two complete and three partial responses in 5/19 patients (26%), and 8 patients (42%) had stable disease. 6 (32%) patients had no response. Median length of complete and partial responses was 3.9 months, and that of stable disease 4.2 months. The main side-effects were thrombocytopenia in 10 patients (53%) and nausea in 6 (32%); the nausea was easily suppressed by ondasetron. Thus, fotemustine-dacarbazine may be new treatment in advanced melanoma.
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PMID:Fotemustine plus dacarbazine in advanced stage III malignant melanoma. 138 16

ImuVert, a new biological response modifier, was evaluated for toxicity and potential efficacy in patients with advanced cancer. This agent consists of sized, labile, natural membrane vesicles associated with ribosomes derived from Serratia marcescens. ImuVert induces enhanced in vitro macrophage and natural-killer-cell-mediated cytotoxicity, and has demonstrated antitumor activity in palpable animal tumor systems. A group of 39 patients with a variety of tumors, 25 men, 14 women, with a mean performance status (Karnofsky) of 80% and median age of 57 years were entered into this trial. ImuVert was administered subcutaneously weekly for a minimum of 3 weeks. A total of 183 treatments were evaluated. Flu-like systemic toxicities, including fever, chills, nausea, vomiting, diarrhea and hypotension were observed. Erythema, induration and tenderness developed at the injection sites. Myelosuppression, thrombocytopenia, anaphylaxis, rental and hepatic toxicities did not occur. All symptoms resolved within 24 h. Two patients with nodular lymphoma achieved a partial response and two minor responses were seen in patients with glioblastoma and melanoma. On the basis of ImuVert's biological activity, and tolerable toxicity it warrants further clinical investigation.
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PMID:Phase I trial of ImuVert (natural membrane vesicles associated with ribosomes) in patients with advanced cancer. 139 37

Thirty-seven patients with advanced malignancies were treated sequentially with recombinant interferon-gamma (rIFN-gamma) and recombinant interleukin-2 (rIL-2) in an outpatient dose escalation clinical trial. rIFN-gamma (0.1 or 0.25 mg/m2/day) was administered by intramuscular injection, days 1-7 and rIL-2 (12, 18, or 24 x 10(6) IU/m2/day) was administered by a 15-min intravenous bolus, days 8-12. Common toxicities encountered included fever, chills, fatigue, neutropenia, and elevations of SGOT, bilirubin, or creatinine. Hypotension and cardiac and pulmonary toxicities were rare. With repeated cycles of therapy, nausea/vomiting and diarrhea associated with the administration of rIL-2 were seen in greater frequency. There were no treatment-related deaths, and no patient required intensive care unit admission for toxicity management. A complete response was observed in one of 11 patients with renal cancer and a partial response was observed in one of seven patients with malignant melanoma. Due to problems with drug supply, further dose escalation could not be continued, and maximum tolerated doses (MTD) were not determined by strict criteria. However, the combination of rIFN-gamma, 0.25 mg/m2/day, and rIL-2, 24 x 10(6) IU/m2/day, appeared to be beyond the MTD, as three of six patients at this dose level could not complete one cycle of therapy due to toxicity. It is unlikely that higher doses of either agent would be tolerated, and for further study using this schedule, we recommend the doses: rIFN-gamma, 0.1 mg/m2/day, and rIL-2, 24 x 10(6) IU/m2/day.
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PMID:A Southwest Oncology Group Phase I study of the sequential combination of recombinant interferon-gamma and recombinant interleukin-2 in patients with cancer. 151 22

Spiroplatin was investigated in a multicenter phase II study, during which the drug was given over 4 h. 64 Patients with nine different solid tumors received 141 cycles of spiroplatin at a dose of 30 mg/m2 every 3 weeks. Most important side effects included nausea, vomiting, myelosuppression, and renal toxicity. Four of 11 evaluable patients with prior cisplatin developed increases in serum creatinine (3 transient, 1 died of renal failure). Of 51 patients without prior cisplatin 2 had a transient increase in serum creatinine levels, and 2 showed persistent changes, in 1 of them leading to hemodialysis. Pre- and posthydration did not reduce drug-induced nephrotoxicity. Only 3 patients showed a response; 1 with renal cell carcinoma, 1 with ovarian carcinoma, and 1 with malignant melanoma. Based on the absence of striking antitumor activity and on the presence of severe unpredictable renal toxicity, the study was stopped prematurely.
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PMID:Multicenter phase II study of spiroplatin. 157 59

We conducted a phase I study of low-dose cyclophosphamide and recombinant interleukin-2 (rIL-2) in 66 patients with advanced cancer resistant to standard therapy. All patients were evaluable for toxicity and 46 patients were evaluable for antitumor response. Patients evaluable for antitumor response included 23 with malignant melanoma, 10 with renal cell carcinoma, 4 with colon cancer, and 9 with various other solid tumors. All patients received i.v. cyclophosphamide (350 mg/m2) on day 1 followed by rIL-2 via 15 min i.v. infusion on days 4-8 and 11-15. The doses of rIL-2 ranged from 6.0 to 36.0 x 10(6) IU/m2. Each treatment cycle consisted of 21 days and a total of 113 cycles was administered. The number of treatment cycles administered per patient ranged from 1 to 8. The dose-limiting toxicities associated with rIL-2 included altered mental status, arthralgias, diarrhea, fatigue, fever, hypotension, nausea/vomiting, and peripheral edema. Twelve patients (18%) were removed from the study secondary to toxicity. Among the evaluable patients, 2 (4%) (malignant melanoma, renal cell carcinoma) developed a partial remission, 13 (29%) maintained stable disease, and 31 (67%) developed progressive disease. We conclude that the combination of low-dose cyclophosphamide and rIL-2 is tolerable in most patients but our data do not suggest an improved response rate for the combination vs. rIL-2 alone.
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PMID:Phase I study of low-dose cyclophosphamide and recombinant interleukin-2 for the treatment of advanced cancer. 159 14

Twenty patients with biopsy-proven metastatic malignant melanoma, previously treated with interleukin-2 (IL-2), received combination chemotherapy for progressive disease. Treatment included carmustine, cisplatin, dacarbazine, and tamoxifen (BCDT). Nausea was the most common toxicity (100%) and usually was mild. Persistent thrombocytopenia was the most frequent toxicity limiting further treatment. Eleven patients (55%) had an objective partial response, three patients (15%) had a minor response, and six patients (30%) had no change or progressive disease in response to this treatment. These results were comparable to the high response rates (21 of 40, 53%) achieved with BCDT in previously untreated patients with melanoma. It was concluded that prior therapy using IL-2 does not significantly alter the response rate of metastatic melanoma to BCDT, thus suggesting that immunomodulators (e.g., IL-2) and chemotherapeutic agents are not cross-resistant treatments.
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PMID:Effective chemotherapy for melanoma after treatment with interleukin-2. 172 71

To date, dacarbazine (DTIC) has been the most effective drug in the treatment of advanced metastatic melanoma, achieving response rates of up to 28% (mean, 21%). Multidrug responses were generally no better than those obtained using monotherapy. A quite promising clinical trial was conducted using the new nitrosourea fotemustine. A total of 19 patients presenting with advanced malignant melanoma (clinical stage IV according to the 1987 UICC classification system) underwent treatment involving a more rapid infusion of the drug and a reduction in the rest period from 5 to 3 weeks. This monotherapy with fotemustine yielded two complete responses and seven partial responses; in addition, four patients showed no change and six cases progressed after the induction cycle (median duration of response to date, 7.6 months, including four cases that have not relapsed). Fotemustine was well tolerated by the patients, with the only mild side effects being thrombocytopenia, leukocytopenia and easily controlled nausea/vomiting. Preclinical studies performed previously indicated that fotemustine inhibits enzymes involved in the ribonucleotide reduction pathway (i.e. DNA synthesis), whereby responding patients (n = 3) appeared to favor the thioredoxin reductase/thioredoxin electron transfer to ribonucleotide reductase, whereas non-responders (n = 4) expressed the alternate glutathione reductase/glutaredoxin mechanism. The 47% response rate obtained in these studies vs the 24% reported previously for fotemustine may reflect variations in enzymes in the ribonucleotide reduction pathway in different patients. However, the efficacy of fotemustine against advanced melanoma warrants more extensive trials of this drug, especially since the quality of life of the patients during and after chemotherapy was not severely affected.
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PMID:Positive phase II study in the treatment of advanced malignant melanoma with fotemustine. 174 55

We studied the safety, tolerance, and clinical effects of the combined administration of subcutaneous recombinant human interleukin-2 and interferon alfa-2b in 54 patients with advanced cancer, for whom no effective standard therapy was available. Treatment courses consisted of a 2-day interleukin-2 pulse (14.4-18 million units (MU) m2/day), followed by 3.6 up to 4.8 MU/m2/day, 5 days per week, over 6 consecutive weeks and interferon alfa-2b at 3 up to 6 MU/m2, administered two-three times weekly for 6 weeks. Overall, patients received more than 90% of the projected dose of interleukin-2 and interferon alfa-2b, respectively. Of 54 evaluable patients (32 renal cell cancer, 12 melanoma, eight colorectal cancer, one B-cell lymphoma, one Hodgkin's disease), four complete responses occurred in patients with renal cell carcinoma, and a greater than 50% reduction in tumour size (partial response) in six renal cell carcinoma patients and one melanoma patient. Moreover, 21 patients (13 renal carcinoma) had stable disease. The median duration of response was 19 months (range 16-22 months) in complete responders. Clinical responses were associated with a mean peripheral blood eosinophil count of more than 1,000/microL (P less than 0.05 versus non-responders). Systemic toxicities included fever, chills, nausea, anorexia, and hypotension limited to WHO grades I and II in more than 80% of patients treated. No treatment-related deaths occurred. This combination of subcutaneously administered recombinant interleukin-2 and interferon alfa-2b has significantly diminished the side effects normally observed with high-dose intravenous recombinant interleukin-2, which requires admission to hospital. It has been shown to induce objective tumour regression in out-patients with progressive metastatic renal cell carcinoma and malignant melanoma.
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PMID:The out-patient use of recombinant human interleukin-2 and interferon alfa-2b in advanced malignancies. 179 91


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