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)

Based on the independent activity of cisplatin, vinblastine, and dimethyl-triazeno-imidazole-carboxamide (DTIC) (CVD), a combination of these agents was used in the treatment of patients with advanced melanoma. Vinblastine was used in a dose of 1.6 mg/m2/d for 5 days, DTIC was used in a dose of 800 mg/m2 intravenously (IV) on day 1, and cisplatin was used in a dose of 20 mg/m2/d for 4 days starting on day 2 of chemotherapy. The courses of chemotherapy were repeated at 3-week intervals. All patients were premedicated with antiemetics, and IV hydration was used before cisplatin. Fifty-two consecutive patients were registered and 50 were evaluable for response. Two patients achieved a complete response (CR) and 18 patients had a partial response (PR) for an overall response rate of 40% (95% confidence interval, 27% to 55%). The median duration of response was 9 months and the median survival time of the responders was 12 months. The overall median survival time of patients treated on this protocol was 9 months. The treatment was associated with significant toxicity consisting of nausea, vomiting, diarrhea, and partial hair loss. Additionally, neutropenia with a median nadir granulocyte count of 500/microliters was observed, and significant anemia required blood transfusions in a majority of the patients after three to four courses of chemotherapy. The dose-limiting toxicity was peripheral neuropathy which required discontinuation of cisplatin after six to eight courses of chemotherapy. We believe that this triple-drug regimen has significant activity that appears to be superior to the single-agent activity of these drugs, both in terms of increased response rate and duration of response.
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PMID:A prospective evaluation of a triple-drug regimen containing cisplatin, vinblastine, and dacarbazine (CVD) for metastatic melanoma. 280 90

Twenty-seven patients with metastatic cancer were treated with a daily continuous intravenous (IV) infusion of recombinant human interleukin-2 (rhIL-2) along with daily intramuscular recombinant interferon-alpha-2a (rIFN-alpha-2a) 4 days per week for 4 weeks with repeated treatment after 2 to 4 weeks of rest. The maximum-tolerated dose (MTD) was 3 million U/m2/d of rhIL-2 with 5 to 10 million U/m2/d of rIFN-alpha-2a. The dose-limiting toxicities are moderate hypotension requiring low doses of pressors and chronic fatigue associated with decreased performance status. Other common side effects included fever, chills, fluid retention, nausea/vomiting, erythrodermia, weight loss, elevated liver transminase levels, anemia, thrombocytopenia, and CNS toxic effects. There were seven objective responses among 25 evaluable patients. Four major responses (one complete response and three partial responses) were observed among 10 patients with melanoma treated with the MTD level. These data suggest that for cancer patients, concomitant rhIL-2 and rIFN-alpha-2a therapy is tolerable and has manageable side effects. Further phase II studies will be needed to define the antitumor activity of this combination.
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PMID:Concomitant administration of recombinant human interleukin-2 and recombinant interferon alpha-2A in cancer patients: a phase I study. 280 85

Forty-two patients with malignant melanoma were treated with doxifluridine, 4000 mg/m2 daily X 5, repeated every 3 weeks. The daily dose was reduced to 3000 mg/m2 in patients who had experienced severe myelosuppression with prior chemotherapy. A total of 35 patients were evaluable for response, and 25 of these received two or more courses. Two responses were observed. Toxicity mainly took the form of nausea, vomiting, stomatitis, dizziness, ataxia, and fatigue. Mild leukopenia was frequent (43%). Nadir counts less than 1.5 X 10(9)/l leukocytes or 50 X 10(9)/l platelets were seen in 7% and 2% of the courses respectively. Doxifluridine has no useful activity against malignant melanoma.
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PMID:Phase II study of 5'-deoxy-5-fluorouridine (doxifluridine) in advanced malignant melanoma. 293 77

Thirty-eight patients with disseminated malignant melanoma (stage IV) who had not received previous chemotherapy were given lomustine 50 to 80 mg/m2 orally on day 1 and dacarbazine 400 mg intravenously on days 1 to 3 with intervals of 6 weeks. Three of the 36 evaluable patients showed complete response (8%), 4 partial response (11%), and 5 had stable disease for at least 3 months (13%). The responding patients had metastases confined to cutaneous, nodal or pulmonary sites. None of the patients with liver, osseous or cerebral metastases, or patients with Karnofsky's status of less than 80, responded. Patients with more than two years from the diagnosis to the start of the chemotherapy were more likely to achieve objective response (p less than 0.05). Eighty-four per cent of the patients had nausea or vomiting, but otherwise toxicity was minimal.
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PMID:Combination chemotherapy with dacarbazine and lomustine in disseminated malignant melanoma. 302 Aug 81

Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, and human leukocyte interferon (IFN-alpha) have synergistic anti-tumor activities in vivo in B 16 melanoma and in vitro against several human cancer cell lines. We have, therefore, carried out a phase I combination study with DFMO plus alpha interferon in the following manner: DFMO was maintained at a steady dose for the first four levels, 1.5 g/m2 every 6 hr. IFN-alpha was given in 100% increments ranging from 0.4 X 10(6)U/m2 to 3.2 X 10(6)U/m2 i.m. daily. At the fifth dose level both IFN-alpha and DFMO were raised by 100 and 50% respectively. From levels one through four the combination was well tolerated with no dose interruptions required because of G.I. toxicity or myelosuppression. However, at dose level 5, one-third of the patients required dose cessation and decrease due to nausea, vomiting and diarrhea. We conclude that for phase II studies the maximal tolerated dose is 3.2 million units of IFN-alpha/m2 and 1.5 g/m2 of DFMO every 6 hr. Of 12 patients with metastatic melanoma, 2 had partial remissions lasting 58+ and 36+ weeks. Two additional patients had minor responses lasting 29 and 32+ weeks. Minor responses were observed in a patient with colon carcinoma and a patient with renal carcinoma. The clinical activity of the combination is currently being pursued in a phase II study among patients with metastatic malignant melanoma.
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PMID:Difluoromethylornithine and leukocyte interferon: a phase I study in cancer patients. 309 71

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

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 authors reported the clinical course and the postmortem examination of a unique case of neurocutaneous melanosis with numerous anomalies and complications, which included congenital dislocation of lenses, hypogonadism, ectopia of prostatic duct, genuine phimose, retentio testis, psina bifida and neurogenic bladder. This 13-year-old boy with a large hairy nevus in a bathing trunk configulation and multiple small nevi over the whole body since his birth was admitted to our hospital for evaluation of headache and vomiting. Neurological examination showed bilateral papilledema and slight left hemiparesis. A CT scan revealed a large right frontal mass and craniotomy was performed with subtotal removal of this tumor which was confirmed as a malignant leptomeningeal melanoma. He initially made uneventful postoperative recovery, and two courses of chemotherapy with DTIC, ACNU and VCR were given; however, the currence of brain tumor ensued shortly thereafter, and he died in approximately six months after the onset of intracranial symptoms despite of the third course of chemotherapy. Thirty five cases of neurocutaneous melanosis associated with or without malignant melanoma have been reported in Japan. Twenty-eight cases were male and 7 female. Two cases showed the evidence of primary malignant melanoma outside of the central nervous system, whereas twenty eight leptomeningeal melanoma, in which 22 were solid and 6 diffuse, were shown intracranially. Other 5 cases had epileptic seizure and/or hydrocephalus caused by wide spreaded leptmeningeal melanosis. This high incidence of intracranial malignant melanoma in this disorder was remarkable compaired with the previous reports in other countries. Mean duration between deaths and the onset of symptoms of intracranial hypertension or focal neurological signs was 7 months, ranging from 1 to 24 months, showing the rapidly deteriorating course in this disorder.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[An autopsy case of neurocutaneous melanosis associated with intracerebral malignant melanoma]. 332 33

Ifosfamide was tested in a phase II study in 12 evaluable patients with advanced malignant melanoma. The drug was administered at the dose of 3 g/m2 on days one and two every 3-weeks. Seven patients were not previously treated and 5 received only minimal prior chemotherapy. Visceral involvement was present in 9 patients, and the remaining 3 had only soft tissue lesions. No patient showed objective tumor response. Mild vomiting was observed in 75% of patients; alopecia occurred in all of them. No other major side effects were observed, in particular, myelotoxicity and urotoxicity. Lack of response advised us to discontinue patient accrual. Our data do not support a therapeutic role of ifosfamide at the given dose schedule in the treatment of metastatic malignant melanoma.
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PMID:Phase II study with ifosfamide in advanced malignant melanoma. 336 70

We have administered 11 to 64 doses of recombinant interleukin-2 (IL-2) ranging from 10,000 to 300,000 U/kg, given three times daily as a bolus infusion through an indwelling Tenckhoff catheter, to seven patients with melanoma, ovarian carcinoma, or colorectal carcinoma. The total IL-2 dose ranged from 800 to 3800 X 10(3) U/kg. Side effects included fever, chills, nausea, vomiting, diarrhea, and major weight gain presumedly related to a capillary leak syndrome. Total weight gain ranged from 5.1 to 17.4 kg and was associated with the development of both peripheral edema and ascites. Marked eosinophilia was noted. Serum IL-2 levels were maintained at 10 to 35 U/mL for up to eight hours following intraperitoneal administration of IL-2. Increases from less than 10(4) cells/mL of a 2-L peritoneal wash to more than 10(6) cells/mL were noted in peritoneal exudate cell yields. Lysis of the natural killer target K562 increased from undetectable levels to as high as 125 lytic units per 10(6) cells. Proliferative capacity to IL-2 increased as much as 30-fold in peritoneal exudate cell yields. In addition, 70% to 80% of the mononuclear cells were T cells (Leu 4+) with intraperitoneal phenotype treatment. A single patient with pulmonary and hepatic metastases showed marked decrease in these lesions with intraperitoneal IL-2 treatment. The other patients treated intraperitoneally with IL-2 did not have significant (greater than 50%) reduction in tumor volume. These findings indicate that the intraperitoneal route of IL-2 administration may allow the in vivo development and expansion of lymphoid cells with antitumor activities.
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PMID:Intraperitoneal administration of interleukin-2 in patients with cancer. 349 95


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