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)

We have conducted a broad phase II clinical trial of chlorozotocin in 74 patients including 28 with malignant melanoma, 18 with breast cancer, nine with non-Hodgkin's lymphoma, six with nonseminomatous testicular cancer, five with ovarian cancer, four with sarcoma, three with non-beta islet cell carcinoma of the pancreas, and one with anaplastic carcinoma of the thyroid. Objective responses were noted only in 15% of the patients with melanoma and in 11% of the patients with non-Hodgkin's lymphoma. Significant leukopenia and thrombocytopenia were observed only in previously treated patients. Chlorozotocin does not appear to offer clinically significant advantages over other currently available nitrosoureas.
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PMID:Phase II trial of chlorozotocin in malignant melanoma, breast cancer, and other solid tumors. 621 Dec 31

Thirty-one patients with metastatic brain tumors (MBT) from lung cancer and ten patients with MBT from melanoma received BCNU, 100 mg/m2, every four weeks by intracarotid and/or vertebral artery infusion into each involved site. Twenty-five patients with lung cancer and all melanoma patients are currently evaluable. Twelve patients with lung cancer had complete and partial responses lasting from 1 to 14 months. Four of them with the histologic diagnosis of small cell carcinoma, one with large cell carcinoma and one with squamous cell carcinoma showed complete response. None of the patients with melanoma MBT experienced any response. All of the patients had periorbital erythralgia and/or occipital pain during the infusion. Four patients manifested mild focal seizures during the infusion or 6 to 24 hours after the treatment. Transient confusion with disorientation was observed in two patients 4 and 24 hours, respectively, after a BCNU infusion. Two patients developed reversible thrombocytopenia after the fifth course of the IA chemotherapy. Median survival of patients with MBT from lung carcinoma was 4 months, with two of them still alive at 10 and 14 months, respectively. Only one patients of the 25 with lung carcinoma died from MBT. Failure to control the primary disease resulted in the deaths of a vast majority of the patients.
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PMID:Phase II study--intra-arterial BCNU therapy for metastatic brain tumors. 626 14

Twenty-two patients with refractory tumors received 64 courses of iv bolus carboplatin every day X 5, every 4-5 weeks. All patients are evaluable for toxicity and 18 are evaluable for response. For solid tumor phase II studies, a dose of 77 mg/m2/day X 5 is recommended for patients who have received prior chemotherapy. Patients with no prior chemotherapy experience should receive 99 mg/m2/day X 5. The major dose-limiting side effect is dose-related thrombocytopenia. Courses of carboplatin on this schedule should be repeated every 5 weeks to avoid cumulative wbc count toxicity, since leukopenia frequently did not occur until Day 28. Other toxic effects observed were nausea and vomiting and lower-extremity myalgias and arthralgias. There was no evidence of hearing loss, mucosal damage, or changes in liver or renal function tests of any patient while in this study. Therapeutic responses were seen in four patients: one partial response in renal cancer of 9+ months' duration; one partial response in head and neck cancer of 7+ months' duration; and objective responses in melanoma and colorectal carcinoma of 6 months' duration.
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PMID:Phase I clinical and pharmacologic trial of carboplatin daily for 5 days. 638 5

Chlorozotocin is a glucose-substituted chloroethyl nitrosourea with pharmacologic properties suggesting it is a relatively nonmyelosuppressive cancer chemotherapy drug. Preclinical studies have shown that this drug possesses approximately twice the in vitro alkylating activity of the chloroethyl nitrosoureas BCNU and CCNU. In the L1210 leukemia system, chlorozotocin has curative activity at doses that result in minimal bone marrow toxicity. In vitro studies of human bond marrow stem cells have shown that chlorozotocin is relatively sparing of these cells compared to BCNU. Phase I and phase II trials in man have been performed that show that chlorozotocin's dose-limiting toxicity is thrombocytopenia at doses greater than 120 mg/m2. In the phase II trial, 16% of patients with colon cancer and 20% of patients with malignant melanoma evidenced objective regression of disease. Chlorozotocin is now undergoing phase II evaluation in combination chemotherapy trials in colon and stomach cancer.
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PMID:Preclinical and clinical studies on chlorozotocin, a new nitrosourea with decreased bone marrow toxicity. 644 66

4-demethoxydaunorubicin (4-dm DNR), a new analog of daunorubicin, was tested at an every 3-week dose schedule in 63 evaluable patients with various forms of disseminated malignancy. Utilizing the intravenous (i.v.) route of administration, the maximum tolerated dose (MTD) was 15-18 mg/m2; with the oral route the MTD was 60 mg/m2. Myelosuppression represented the dose-limiting factor, and leukopenia was more often observed than thrombocytopenia. However, leukopenia was more frequently detected following i.v. administration while vomiting represented the most frequent toxic sign after oral administration. Loss of hair was moderate with either route of administration and comparatively less frequent and pronounced than that observed after doxorubicin (DX) and its analog 4'-epi-doxorubicin (4'-epi-DX). Aside from transient aspecific electrocardiographic changes recorded in 30% of patients, no cardiac toxicity was documented. Tumor response was documented in seven patients with malignant lymphomas, breast cancer, melanoma and carcinoma of uterine cervix. Two out of the seven responders achieved prolonged complete remission and four were resistant to doxorubicin. 4-dm DNR appears to be an analog worth further clinical trials.
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PMID:Phase I study of 4-demethoxydaunorubicin. 659 May 30

Sixteen patients, 13 of whom had received prior chemotherapy, were treated with vindesine for advanced malignant melanoma. Previous treatment included vinca alkaloids in six. Thirteen patients received vindesine, 4 mg/m2 and three received vindesine, 3 mg/m2 by weekly I.V. injection. There were two partial (12%) and no complete responses among all of the patients. Both responses occurred in subcutaneous lesions and lasted for 4 and 6 weeks, respectively. Fifteen patients could be evaluated for treatment-related toxicity. The most common side effect was modest leukopenia (less than 3000/microliter) in 10 patients (67%). The lowest leukocyte count recorded was 1100/microliter. Thrombocytopenia was not encountered. Neurotoxicity, manifest most commonly as mild or moderate peripheral paresthesiae, was seen in eight patients (53%).
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PMID:Vindesine for metastatic malignant melanoma. A phase II trial. 661 21

Five inoperable invasive cases of malignant melanoma of the maxillofacial region were treated with seven intracarotid artery infusions of DTIC. Total doses of 3.5-9.5 g of DTIC were continuously administered for 15-25 days. Two of the five patients experienced transient objective regression after the first DTIC infusion but not after the second. Three patients were operated on after infusion and only one had recurrence. However, all patients died with disseminated disease within 3 years after DTIC infusion. Toxicity was encountered in two of seven infusions; it consisted in reversible leukopenia plus thrombopenia and leukopenia alone. These patients had received the highest doses, 9.5 g/25 days and 8 g/20 days respectively. It is concluded that intra-arterial infusion of DTIC can be temporarily effective in the polydisciplinary treatment of invasive head and neck melanomas.
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PMID:Intracarotid artery infusion of DTIC for invasive maxillofacial melanoma. 664 95

Because Cisplatin potentiates the effect of radiotherapy in animal tumor systems and because Cisplatin is capable of causing regressions of human malignant melanomas, a study was initiated in patients with malignant melanoma metastatic to brain to investigate the feasibility of administering Cisplatin once a week during cranial irradiation. Cisplatin 40 mg/m2/week (three doses) was given I.V. to 18 patients during whole brain irradiation, 3 000 rads in 12 fractions over 21/2 weeks. Eleven patients also received Cisplatin 120 mg/m2 every three weeks, starting three weeks after cranial irradiation. Median survival was ten weeks, and only one of 13 patients whose brain metastases had not been resected experienced neurological and CT scan improvement. Thirteen patients have died, and brain metastases were a major cause. No regression of extracerebral tumor was seen in 15 patients with evaluable extracerebral lesions. During weekly low-dose Cisplatin administration, nausea and vomiting were moderate to severe. No granulocytopenia was noted, although three courses were associated with mild thrombocytopenia. Mucositis, peri orbital swelling, vertigo, and headache were each noted in two of 51 courses of treatment and seizures, ototoxicity, pancreatitis, and hiccups were each noted in one course. Renal toxicity and ototoxicity each developed in three of the 11 patients receiving Cisplatin 120 mg/m2, and nausea and vomiting were severe.
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PMID:Weekly Cisplatin during cranial irradiation for malignant melanoma metastatic to brain. 668 94

A phase II trial was conducted to determine the clinical activity of amsacrine (m-AMSA) in patients with heavily pretreated solid tumors, myeloma, and lymphoma at the University of Arizona Cancer Center. Additionally, m-AMSA was evaluated at other Southwest Oncology Group institutions in breast cancer, myeloma, melanoma, and oat cell cancer of the lung. At a dose of 120 mg/m2 given iv every 28 days, 12 partial responses were observed in 221 patients evaluable for response. Some antitumor activity was observed in breast cancer (four responses of 65 patients), non-Hodgkin's lymphoma (three of nine), Hodgkin's disease (two of five), and sarcoma (two of 15). A partial response was also documented in one of two patients with cervical cancer. Among the 135 patients treated at the University of Arizona who were extensively evaluated for toxic effects, only myelosuppression and anemia were seen in a significant number of patients. At this dose and schedule, 29% of patients developed leukopenia of less than 3000 cells/mm3, 16% developed a thrombocytopenia of less than 100,000 cells/mm3, and 29% had an acute fall in hemoglobin of greater than or equal to 2 g/100 ml. In addition, two patients suffered grand mal seizures which were not clearly drug-related. These results suggest that further study of m-AMSA in lymphoma, sarcoma, and cervical cancer is warranted.
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PMID:Phase II evaluation of amsacrine (m-AMSA) in solid tumors, myeloma, and lymphoma: a University of Arizona and Southwest Oncology Group Study. 668 99

To evaluate the incidence of thrombocytopenia and bleeding among patients with solid tumors treated intensively with chemotherapy, the records of 1274 patients treated between 1972 and 1980 on protocols known to produce significant myelosuppression were reviewed. Three hundred one patients with solid tumors (breast, lung, melanoma, sarcoma, primary brain, testicular, hypernephroma and others) experienced 5063 days of thrombocytopenia (platelet count less than 50,000/microliters) and 670 days of severe thrombocytopenia (platelet count less than 20,000/microliters). The median number of days thrombocytopenia was 6 (range, 1-250). There were only 44 episodes of clinically detectable serious bleeding, primarily gastrointestinal (26/44), during thrombocytopenia and all but seven episodes first occurred at platelet counts between 20,000-50,000/microliters. Fifteen of the 44 bleeding episodes were associated with coagulation abnormalities, 24 occurred during serious infection, and 12 occurred at sites of tumors. One hundred forty-seven of the 301 patients (49%) received platelet transfusions. In 86 thrombocytopenic patients with central nervous system (CNS) tumors, there was no evidence of CNS bleeding during thrombocytopenia. Hemorrhagic deaths were uncommon, and of the 12 patients who died of bleeding, 7 had normal counts. There is a very low incidence of significant thrombocytopenia or bleeding among patients with solid tumors treated with combination chemotherapy or experimental agents escalated to maximally tolerated doses. These data suggest that with respect to thrombocytopenic bleeding intensive treatment of patients with solid tumors can be pursued with relative safety utilizing the standard transfusion supportive measures now widely available.
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PMID:Incidence of thrombocytopenia and serious hemorrhage among patients with solid tumors. 669 60


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