Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One hundred twenty patients with metastatic malignant melanoma were randomized to receive either cyclophosphamide, 600 mg/m2 IV, on day 1 plus DTIC 200 mg/m2 IV days 1 through 5, or the same chemotherapy plus C. parvum 5 mg/m2 IV on day 8 and day 15. Therapy was repeated every 21 days. Although responses were observed in 13.8% of patients on cyclophosphamide plus DTIC versus 25.5% of patients on cyclophosphamide plus DTIC plus C. parvum, the median duration of remission was 15.6 weeks on chemotherapy and 13.0 weeks on chemotherapy plus C. parvum. Furthermore, survival was similar on both regimens (6.1 months versus 5.7 months, respectively). Favorable prognostic factors included metastatic disease confined to skin or lymph nodes (33% responses), performance status greater than 70% (24% response rate), and administration of three or more courses of chemotherapy (31% response rate). The dose limiting toxicity was myelosuppression, which was equal on both regimens. Chills and fever were common in response to C. parvum, and, rarely hypotension, cyanosis, or immune nephritis was observed. The addition of C. parvum to chemotherapy with cyclophosphamide plus DTIC is not recommended.
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PMID:Cyclophosphamide plus 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) with or without Corynebacterium parvum in metastatic malignant melanoma. 38 76

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