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 phase I study of weekly semustine was conducted in 32 patients with advanced cancer. Doses were escalated from 18 to 36 mg/m2/week. At a dose of 36 mg/m2/week, 43% of the patients developed platelet counts less than 100,000/mm3 after a median of 20 weeks on study, and 25% developed wbc counts less than 3000/mm3 after a median of 16 weeks on study. Drug-related nausea was reported by only one patient and was the only subjective toxic effect reported. Tumor regressions were noted in patients with adenocarcinoma of the colon, melanoma, and mixed adenocarcinoma and squamous cell lung cancer. A reasonable starting dose for phase II studies is 36 mg/m2/week, with dose adjustments based on platelet and wbc counts.
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PMID:Phase I evaluation of semustine in a weekly schedule. 686 Nov 64

Acivicin, an L-glutamine antagonist, was administered to 37 evaluable patients with refractory advanced solid tumors in a phase I trial. A total of 67 evaluable 72-hr iv infusions were given at 3- to 4-week intervals. Doses ranged from 3.0 to 90 mg/m2/course. Reversible CNS toxicity was dose-limiting and included lethargy, somnolence, anxiety, hallucinations, and paranoid psychoses. Four of five patients experienced unacceptable CNS toxicity at 90 mg/m2. Three of eight patients experienced reversible diaphoresis and chills without fever at 75 mg/m2, and two had dizziness and ataxia. Hematopoietic toxicity, nausea, emesis, and diarrhea were mild and dose-related. One patient developed a blue-green discoloration of the infusion arm. Serial plasma and urine specimens from 13 patients were assayed for acivicin using a microbiologic method. Peak plasma levels at the end of the 72-hr infusions correlated with dose and ranged from 0.09 to 1.10 microgram/ml. When data from six patients were fitted to a two-compartment open model, alpha-half-life ranged from 1.1 to 63 mins, while beta-half-life ranged fro 338 to 629 mins. Renal clearance ranged from 6 to 24 mL/min, and nonrenal clearance accounted for 58%-83% of the total drug clearance. CNS toxicity correlated with plasma acivicin levels which exceeded 0.9 microgram/ml for greater than 16 hrs, but not with peak plasma levels or with the integrals of the concentration x time curves. Minor responses were seen in one patient with melanoma, in one with epidermoid pulmonary carcinoma, and in two with colon carcinoma. A starting dose of 60 mg/m2/course was recommended for phase II trials, with possible escalation to 75 mg/m2 in the second course if the drug was well-tolerated.
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PMID:Phase I trial and pharmacokinetics of acivicin administered by 72-hour infusion. 687 83

A phase II study of methanesulfonamide, N-(4-(9 acridinylamino)-3-methoxyphenyl)-(m-AMSA) was undertaken by the Eastern Cooperative Oncology Group. Thirty-five evaluable patients were studied, 18 of whom had had no prior therapy and eight of whom had been treated only one cytotoxic drug. Thirty-one of these patients were ECOG performance status 2 or better. The dose of m-AMSA employed in this study was 40 mg/M2 as an I.V. infusion over 20 minutes daily for 3 days, repeated every 3 weeks. Leukopenia was found to be dose-limiting; thrombocytopenia and anemia were also observed. Other prominent toxicities included anorexia, nausea, and vomiting. No cardiovascular toxicity was observed in this study, but none of the patients had received prior anthracycline therapy. Only one partial response of measurable disease was observed, all other patients had progressive disease on m-AMSA therapy. No significant clinical activity of m-AMSA against malignant melanoma was demonstrated in this very favorable group of patients.
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PMID:Phase II study of m-AMSA in advances malignant melanoma. 689 95

AMSA, an acridine derivative with significant antitumor activity in experimental tumors, was administered to 17 patients with advanced tumors refractory to standard chemotherapies. A phase I study was undertaken in 10 patients with solid tumors and lymphomas. Dose-limiting toxicity was myelosuppression. With a median dose of 90 mg/m2 (75-148 mg/m2), median lowest WBC count was 1,000/mm3 (100-3,200) on day 11 and its recovery up to 4,000/mm3 was seen on day 21, while lowest platelet count was 42 X 10(3)/mm3 (7-300 X 10(3) on day 12 and its recovery up to 100 X 10(3)/mm3 was on day 20. Non-hematological toxicities were nausea (39%), vomiting (11%) and phlebitis (17%) in 18 courses of therapy. The result indicated that the recommended dose schedule for a phase II evaluation was 90 mg/m2, every three weeks. Therapeutic activity was observed in patients with non-Hodgkin's lymphoma (one partial response and two minor responses out of four). Two out of five breast, one ovarian, and one melanoma patients showed stable diseases. Five leukemic patients (three AMLs, one MoL, and one blastic CML) were treated with AMSA, and in these cases cytoreduction of peripheral and bone marrow blasts was seen, but it was not adequate to induce remission. Further clinical trials with this agent are warranted, especially in patients with acute leukemia, lymphoma and breast cancer.
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PMID:[Phase I-II studies of a new antineoplastic agent, 4'-(9-acridinylamino)-methanesulfon-m-anisidide (AMSA)]. 689 58

A 33-year-old woman with malignant melanoma well responded to a chemotherapy including DTIC, ACNU, and VCR, and intralegional injection of OK-432. Four years prior to admission, a lentigo of 5 mm diameter at her left frontal chest was found, but, histological examination resulted in no distinctly malignant findings. In November 1979, multiple subcutaneous tumors appeared over posterior surface of the chest and left axillar region, which were gradually increasing in number and size, then she was admitted to our hospital in June, 1980. Biopsy of subcutaneous tumors revealed a malignant melanoma and its metastasis to skin. Immunochemotherapy was started immediately based upon this diagnoses. The patient received 100mg DTIC i.v. for 4 days, 100mg ACNU i.v. for one day and 1 mg VCR i.v. for one day. OK-432 was locally injected into some tumors as an immunotherapy. On completion of the third course of chemotherapy, all subcutaneous tumors were decreased in size, especially the tumors injected with OK-432. However, patient didn't respond to a repeated chemotherapy, thereafter malignant melanoma was metasized to uterus and peritoneum in May, 1981, and she died in September, 1981. Major side effects of this chemotherapy were nausea and mild transient leukocytopenia. The combination of chemotherapy including DTIC and local injection of OK-432 appeared to be effective for malignant melanoma.
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PMID:[A case of malignant melanoma responded to chemotherapy including DTIC and local injection of OK-432]. 696 31

Forty-four patients with metastatic brain neoplasms received glycerol instead of corticosteroids during periods of brain irradiation. Headache, nausea, and vomiting were controlled in more than 90% of symptomatic patients, while paralysis, confusion, and papilledema improved in 55% to 80%. Patients with minimal or no symptoms remained stable. Patients with moderate or severe symptoms had significant improvement during the first week and substantial improvement during the second week of treatment. Glycerol did not induce immunosuppression when administered in combination with radiotherapy and chemoimmunotherapy. Patients with malignant melanoma had longer survival when treated with glycerol instead of corticosteroids.
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PMID:Glycerol: an alternative to dexamethasone for patients receiving brain irradiation for metastatic disease. 699 10

In a Phase I trial patients with advanced malignant melanoma were treated with high-dose nitrogen mustard (HN2) and autologous bone marrow transplantation. Three patients were entered into the protocol. After procurement of 1.1--5.5 x 10(5) committed stem cells (CFU-C) per kg body wt, 33 mg/m2 of HN2 was administered i.v. as a bolus. Forty-eight hours later the noncryopreserved bone marrow was reinfused i.v. Side effects consisted of nausea, vomiting, anorexia, alopecia, phlebitis, hepatotoxicity, and neurotoxicity. Cardiotoxicity and hypocalcemia were encountered as unanticipated side effects not described so far by using lower dosages of HN2. Granulocytopenia of less than 10 x 10(9)/l and thrombocytopenia of less than 50.0 x 10(9)/l lasted for a mean of 10 and 8 days, respectively. Measureable disease present in two of three patients did not respond to the dose of HN2 used in this protocol. This study shows that hematologic recovery was shorter than previously reported in studies using HN2 without autologous bone marrow transplantation. The nonhematologic side effects of this dose of HN2, however, were severe and preclude the use of higher doses.
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PMID:High-dose nitrogen mustard (HN2) with autologous nonfrozen bone marrow transplantation in advanced malignant melanoma. A phase I trial. 701 56

Seventeen patients with disseminated malignant melanoma received a daily oral regimen of tamoxifen, 100 mg/m2. All patients had prior chemotherapy and predominantly visceral involvement. None of the patients had an objective regression and most (71%) had progressive disease at the time of first reassessment. Moderate to severe nausea occurred in 24% of patients. In the dose and schedule used in this study, tamoxifen is ineffective in patients with advanced malignant melanoma and prior chemotherapy exposure.
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PMID:Phase II study of high-dose tamoxifen (NSC-180973) in patients with disseminated malignant melanoma. 705 50

Plasmapheresis has been performed in 16 patients with advanced malignant disease (12 malignant melanoma, 2 breast cancer, 2 colon cancer). Up to 3,000 ml of plasma (range 1,650-3,000 ml) have been replaced by one single plasma exchange. Side effects observed in about 50% of the patients were mainly nausea and chills. Serum proteins including acute phase reactants were monitored before and 2, 4, and 7 days after plasma exchange. A transient change of these proteins was observed in the first days, but, later on, pretreatment values were always retained. Peripheral blood lymphocyte blastogenic response to mitogens was increased in 5 out of 9 patients 7 days after plasma exchange. In 7 out of 9 patients pretreatment serum was found inhibitory to autologous lymphocyte reactivity to mitogens. Furthermore, plasmapheresis was found to decrease significantly the blocking effect of patients' sera on normal donor lymphocyte reactivity. Plasmapheresis was found tolerable in all patients treated, but without any clinical efficacy. Further studies are warranted to establish the therapeutic value of plasma exchange in patients with advanced malignancies.
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PMID:Plasmapheresis in patients with advanced malignant disease: a pilot study. 707 38

Twenty-eight patients with disseminated malignant melanoma, who had failed prior therapy, were treated with aziridinylbenzoquinone (AZQ) administered on a 5-day I.V. schedule repeated every 4 weeks. The starting doses were 8 or 6 mg/m2/day x 5 days for good-and-poor-risk patients respectively. There were no complete or partial responses among 23 evaluable patients but four patients had stabilization of disease. The dose-limiting toxicity was thrombocytopenia. Other toxicities included weakness, nausea, vomiting, anorexia, dizziness, abdominal pain, and constipation. AZQ, given on a 5-day schedule, is ineffective in the treatment of patients with metastatic malignant melanoma.
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PMID:AZQ therapy in patients with disseminated malignant melanoma. 716 3


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