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 comparison has been made of the effects of three nitrosoureas (BCNU, CCNU, and methyl-CCNU) on the cells of Lewis lung carcinoma and B16 melanoma in vivo using a new in vitro method for assaying colony-forming cells. In addition, the effect on early hemopoietic precursors has been studied using the in vivo spleen colony assay and the in vitro agar colony assay. The results show that the three nitrosoureas are selective against Lewis lung carcinoma and B16 melanoma relative to normal hemopoietic precursors. Furthermore, the effect of these nitrosoureas is unchanged when the rate of proliferation of the hemopoietic precursor cells is increased.
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PMID:Differential sensitivity of colony-forming cells of hemopoietic tissue, Lewis lung carcinoma, and B16 melanoma to three nitrosoureas. 120 97

The treatment of disseminated melanoma with monotherapy and combined chemotherapy is still associated with rather low objective response rates and significant toxicity. Therefore, more effective substances and regimens with less toxicity are desired in the pharmacologic treatment of metastatic melanoma. The initial high expectations placed in systemic cancer treatment with interferons (IFNs) were not fulfilled, but IFN-alpha as a single substance revealed an objective response rate of 10% to 15% in melanoma patients. Clinical and experimental results suggest that the antitumoral activity of IFNs is mainly related to their antiproliferative effect, whereas immunomodulatory effects were not substantiated in clinical investigations. Results of in vitro trials showed that type-I IFNs may produce antagonistic effects combined with some agents (eg, cisplatin) and synergistic effects combined with others (eg, vindesine and BCNU). Clinical trials with combined IFN and cytostatic drug therapy were started a few years ago and have yielded promising initial results. Several studies with an entire number of more than 200 patients have already been performed to evaluate the combination of IFN-alpha and dacarbazine. This regimen was effective in over 50% of the patients, leading to complete or partial remissions in 27% and stabilization of the disease in an additional 28%. Toxicity is significant but still manageable, especially with a new generation of antiemetic drugs (serotonin receptor blockers). Several clinical trials performed so far did not find an improved efficacy by adding IFN-alpha to cisplatin or to vinblastine. The combination of IFN-alpha and vindesine seems to be more favorable and superior to the response rates of single agents and was well tolerated in an ongoing trial in our clinic. Recently, a new generation of multidrug combinations including IFN-alpha has been initiated and several reports with overall response rates greater than 50% have been published. In conclusion, combined regimens with IFN-alpha and different cytostatic drugs seem to be superior to treatments with cytostatic drugs alone and rather safe in disseminated melanoma. Additional combinations of IFNs and cytostatic drugs should be evaluated in future in vitro studies and in clinical trials.
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PMID:Combined treatment of metastatic melanoma with interferons and cytotoxic drugs. 137 65

The recently synthesized nitrosourea, N-[N'-chloro-2-ethyl-N'-nitrosocarbamoyl]-S-methyl cysteamine sulfoxide (Perrimustine), is water soluble and has a high alkylating activity, similar to that of the widely used nitrsoureas BCNU and CCNU, and a low carbamoylating activity. Preclinical studies with a broad spectrum of murine tumors indicate that this new compound may be clinically useful. The maximally efficient dose range (MEDR) in L1210 bearing mice was 45 mg/m2 (subcurative dose) to 67 mg/m2 (subtoxic dose). The present phase I trial used an intrapatient escalation schedule, so that each patient entering the study received a potentially active dose. The first dose injected was 1:100 of the MEDR suboptimal dose to check for anaphylactic sensitivity. Patients were then given increasing doses at increasing time intervals until toxicity was observed. The highest dose was given on day 150-230. The main toxic effect was myelosuppression [five out of the 24 patients evaluated: one grade 4 thrombocytopenia, two grade 3 thrombocytopenia; anemia and leucopenia were milder (grade 1 to 2 on OMS scale)]. Of the 19 patients evaluated for clinical response, one showed response after the 45 mg/m2 dose (disappearance of the cerebral metastasis with persistence of hepatic localizations in a patient with melanoma) and the disease was stabilized in two cases (a pleural mesothelioma and a renal carcinoma with lung metastases) after 26 and 37 weeks, with total cumulative doses per m2 of 232 and 196 mg, respectively.
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PMID:Phase I trial of Perrimustine, a new cysteamine (2-chloroethyl) nitrosourea: an intrapatient escalation scheme. 152 2

Laboratory data suggest a synergistic interaction between carmustine (BCNU) and tumour necrosis factor (TNF) in melanoma. We therefore studied the activity of 200 mg/m2 BCNU given alone or in combination with 88 micrograms/m2 recombinant human TNF-alpha (rhTNF alpha) as a daily i.v. infusion for 5 days at 48-day intervals to patients with metastatic melanoma. In this randomised phase II trial, the rate of response to BCNU alone was 20% [95% confidence interval (CI), 2%-38%], and this was not improved by the addition of TNF (response rate, 10.5%; 95% CI, 1.3%-33%). Toxicity was higher in the combination arm, and there was no difference in survival.
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PMID:A randomised phase II study of carmustine alone or in combination with tumour necrosis factor in patients with advanced melanoma. 158 84

Modern aspects of treatment for malignant melanoma, basalioma and cutaneous lymphomas are reviewed. Cytokines have been proposed as immunostimulants in adjuvant therapy (destruction of residual tumor) for malignant melanoma or at high doses for treatment of metastatic melanoma. Basalioma is the most common tumor of the skin, prone to recurrence because of its iceberg-like subclinical growth-pattern. Micrographic surgery is best adapted to this growth behaviour by following the extent of the tumor in all directions by special histopathologic techniques thus permitting radical excision. Primary lymphomas of the skin although rare (1 in 100,000 per year) prevail and cumulate because of the long course over years and decades. New treatment avenues have opened by topical use of phospholipids and cytostatic drugs i. e. carmustine (BCNU).
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PMID:[Current treatment methods in skin tumors]. 158 75

Fourteen consecutive patients with stage IV metastatic melanoma with measurable disease were treated between January 1989 and August 1990 with combination chemotherapy. The chemotherapy regimen (DBPT) included dacarbazine (DTIC) 200 mg/m2/i.v. on days 1 through 3, carmustine (BCNU) 150 mg/m2/i.v. on day 1, cisplatin 25 mg/m2/i.v. on days 1 through 3, and tamoxifen citrate 10 mg p.o. twice daily. This cycle was repeated every 4 weeks. BCNU was given every other cycle. A total of six cycles of chemotherapy were delivered. Patients were then restaged to assess the response. Six concurrent patients during the study period did not elect to undergo chemotherapeutic approach and served as control subjects. When evaluated at 300 days of follow-up, 4 patients had response (3 complete response and 1 partial response), 3 had stable disease, and 7 showed progression. At 300 days of evaluation after chemotherapy, survival appeared significantly increased between treated and nontreated groups, that is, 48% in the chemotherapy group versus 27% in the control group (p = 0.03). Actuarial survival was significantly increased between those who responded to chemotherapy versus the nonresponders. At 300 days follow-up, survival was at 83% in the responders and 22% in nonresponders (p = 0.0002). This study shows that in stage IV disease, systemic chemotherapy appears to make a difference in survival. Attempts to discover better chemotherapy regimens to improve response in patients with stage IV malignant melanoma should continue to be rewarded.
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PMID:Treatment of stage IV malignant melanoma with dacarbazine, carmustine, cisplatin, and tamoxifen regimens: a University of South Florida and H. Lee Moffitt Melanoma Center Study. 164 9

In a consecutive series of studies, 164 patients with symptomatic and/or visceral metastatic malignant melanoma were treated with single agent vindesine, high dose melphalan with autologous bone marrow transplantation (AMBT), high dose BCNU with ABMT or the BOLD (bleomycin, vincristine, CCNU and DTIC) combination. The high dose treatments and the combination chemotherapy resulted in significantly higher response rates but no prolongation of survival. Factors associated with longer survival included the absence of visceral metastases, the absence of bulky disease and good performance status. For all treatments, life table estimates of survival at 1 and 2 years were only 10% and 4% respectively.
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PMID:Chemotherapy for malignant melanoma: combinations and high doses produce more responses without survival benefit. 169 22

Twenty-three patients with malignant melanoma metastatic to the central nervous system (CNS) were treated with intracarotid cisplatin-based chemotherapy. Twenty-two had failed prior cranial radiation therapy (one patient refused radiation therapy) and had progressive brain metastases documented by computerized tomography (CT). Intracarotid cisplatin 40-75 mg/m2 was administered alone (seven patients) with 1,3-bis(2-Chloroethyl)-1-nitrosourea (BCNU) (13 patients) or bleomycin (three patients). Courses were repeated monthly with CT scan. Seven patients (30%) had objective improvement in CT scans and three patients (13%) had stabilization of disease. The median time to tumor progression for responding patients was 20 weeks (range 8-34 weeks) while stable disease ranged from 9-12 weeks. In three patients the extracranial disease progressed while the brain metastases responded. Neurological and retinal toxicity were potential complications of therapy. Intracarotid cisplatin-based chemotherapy may be useful for palliation in selected patients with malignant melanoma and CNS metastases.
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PMID:Intracarotid cisplatin-based chemotherapy in patients with malignant melanoma and central nervous system (CNS) metastases. 169 2

High levels of intracellular glutathione (GSH) may result in resistance of tumor cells to cytotoxic drugs. Because of the innate refractory nature of melanoma cells to chemotherapy, we have used a syngeneic murine system consisting of nontumorigenic Mel-ab melanocytes, tumorigenic H-ras-transformed melanocytes (C9.1), and the highly metastatic BL6 melanoma cells to examine the GSH content, glutathione S-transferase (GST) activity, and sensitivity to buthionine sulfoximine (BSO) and other cytotoxic drugs. Compared to the nontumorigenic melanocytes, both C9.1 and BL6 melanoma cells have nearly fivefold higher GSH content, and BL6 cells have increased GST activity. C9.1 and BL6 cells are more resistant to the cytotoxic effects of BCNU and adriamycin; however, the degrees of resistance do not reflect the increased GSH content in these cells. Pretreatment of BL6 melanoma cells with 50 microM BSO depleted over 90% of their GSH content and enhanced the growth-inhibitory effects of L-dopa methylester, BCNU, bleomycin, and dacarbazine. Exposure to BSO alone was not toxic to the tumor cells for up to 24 hr, but was significantly cytotoxic in the melanocytes after 9 hr. The sensitivity of these cells to BSO appears to depend on a critical level of GSH depletion which is not related to the initial GSH content. These studies suggest that the resistance of melanoma cells to cytotoxic drugs is only partially attributed to changes in the GSH system caused during cellular transformation.
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PMID:Differential sensitivities of murine melanocytes and melanoma cells to buthionine sulfoximine and anticancer drugs. 182 27

Cerebral metastases of malignant melanoma are correlated with a very poor prognosis. Surgery of an isolated metastase can lead to a long survival but the brain lesions are frequently numerous and associated with an extracerebral diffusion. Dacarbazine (DTIC) gives a mean response rate of 21% on visceral localisations but doesn't cross the blood brain barrier (BBB). Neither do the biological response modifiers like Interleukin 2 (Il2) that leads to 25% response rate in disseminated melanoma. Nitrosoureas like carmustine (BCNU) and semustine (CCNU) have been investigated in different non randomised studies and the clinical results didn't illustrate their theorical ability to cross the BBB. Radiotherapy is also used as a palliative therapy with 7 to 16 weeks survival. Fotemustine (muphoran), a new amino acid linked nitrosourea, can give a response rate up to 28.2% in patients with cerebral metastases and the increased survival of responding patients is significant. The availability of this new drug may suggest associations with surgery and radiotherapy in the future to improve the survival of such patients.
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PMID:[Brain metastases of malignant melanomas]. 185 2


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