Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0278883 (metastatic melanoma)
 6,224 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-five patients with measurable metastatic melanoma refractory to DTIC and a nitrosourea were treated with dibromodulcitol (DBD). DBD was administered orally at bedtime at a dose of 100 mg/m2/day until hematologic toxicity (a greater than or equal to 50% decrease in the wbc or platelet count) was induced. Five patients experienced clinically useful objective remissions; responding lesions included both soft tissue metastases and visceral metastatic disease. It is concluded that DBD is useful in the treatment of patients with metastatic melanoma and thus joins DTIC and the nitrosoureas as single agents which are active against this malignancy.
 ...
PMID:Positive phase II trial of dibromodulcitol in patients with metastatic melanoma refractory to DTIC and a nitrosourea. 75 17

Seventeen patients with histologically proven melanoma and measurable metastatic disease received 7-week cycles of fotemustine 100 mg/m2/day on days 1 and 8, and decarbazine (DTIC) 500 mg/m2/day on days 15 and 16, in a prospective open study, to assess the efficacy of fotemustine-DTIC combination. Response rate was 11.7%: one partial response (PR) in brain for 4.5 months, and one PR in brain and lymph nodes for 4 months. There was also one (5.8%) minimal response (MR) in brain, stomach, and lymph nodes for 8 months, and three (17.6%) patients with stable disease. Survival of responders was significantly superior to nonresponders. There was no response in brain without response in extracerebral sites. Toxicity was generally mild and well tolerated by all the patients. Fotemustine-DTIC showed some activity against metastatic melanoma, and should be further evaluated.
 ...
PMID:Fotemustine and DTIC combination in patients with disseminated malignant melanoma. 155 85

A 43-year-old female with metastatic melanoma was treated with a combination chemoimmunotherapeutic regimen of DTIC with interleukin-2. Three days after cessation of her interleukin-2 she developed a rapid onset quadriparesis. Computed tomographic scanning failed to show any intracranial pathology but magnetic resonance imaging demonstrated the presence of multiple foci of cellular infiltration. The patient gradually recovered both clinically and radiologically over the following three months. The nature of these infiltrative foci remains uncertain; however, they are unlikely to have been of neoplastic origin and may be due to interleukin-2-induced lymphocytic infiltration. Whenever possible, we suggest that assessment of cerebral involvement with metastatic disease in these patients be by magnetic resonance if initial computed tomography is negative.
 ...
PMID:Multifocal neurotoxicity during interleukin-2 therapy for malignant melanoma. 155 27

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.
 ...
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

To date, dacarbazine (DTIC) has been the most effective drug in the treatment of advanced metastatic melanoma, achieving response rates of up to 28% (mean, 21%). Multidrug responses were generally no better than those obtained using monotherapy. A quite promising clinical trial was conducted using the new nitrosourea fotemustine. A total of 19 patients presenting with advanced malignant melanoma (clinical stage IV according to the 1987 UICC classification system) underwent treatment involving a more rapid infusion of the drug and a reduction in the rest period from 5 to 3 weeks. This monotherapy with fotemustine yielded two complete responses and seven partial responses; in addition, four patients showed no change and six cases progressed after the induction cycle (median duration of response to date, 7.6 months, including four cases that have not relapsed). Fotemustine was well tolerated by the patients, with the only mild side effects being thrombocytopenia, leukocytopenia and easily controlled nausea/vomiting. Preclinical studies performed previously indicated that fotemustine inhibits enzymes involved in the ribonucleotide reduction pathway (i.e. DNA synthesis), whereby responding patients (n = 3) appeared to favor the thioredoxin reductase/thioredoxin electron transfer to ribonucleotide reductase, whereas non-responders (n = 4) expressed the alternate glutathione reductase/glutaredoxin mechanism. The 47% response rate obtained in these studies vs the 24% reported previously for fotemustine may reflect variations in enzymes in the ribonucleotide reduction pathway in different patients. However, the efficacy of fotemustine against advanced melanoma warrants more extensive trials of this drug, especially since the quality of life of the patients during and after chemotherapy was not severely affected.
 ...
PMID:Positive phase II study in the treatment of advanced malignant melanoma with fotemustine. 174 55

Twenty-five assessable patients with metastatic melanoma have been entered in a multicenter phase II study of two induction cycles of human recombinant interleukin-2(IL2), 18 x 10(6) IU/m2/d continuous intravenous (IV) infusion on days 1 to 5 and days 12 to 17. Dacarbazine (DTIC), 850 mg/m2 IV bolus was given on day 26. The cycle was repeated at 5 weeks. Maintenance therapy was scheduled 3 weeks after the completion of induction treatment, consisting of IL2, 18 x 10(6) IU/m2/d for 5 days alternating with DTIC, 850 mg/m2 IV every 3 weeks, for a total of 18 weeks. Six patients responded (24%); two complete and four partial. Stable disease was seen in five patients. None of the six patients with more than two sites of metastases responded. Maximum response was observed in the first 3 months of treatment. Progression-free periods of 6 months and longer were seen in the two complete responders (8 and 17+ months), in two of the four partial responders (7 and 12+ months), and in three of the five patients with stable disease (9+, 15, and 17+ months). Toxicity included fever, skin rash, fatigue, anorexia, and diarrhea in most patients. Two patients had a weight gain of more than 10%. Eight patients needed intensive care for the observation and treatment of a myocardial injury (one patient), ventricular tachycardia (one), hypotension and oliguria (four), and sepsis (two). Sequential treatment with IL2 and DTIC appears to be effective but not clearly better than could be expected of IL2 alone.
 ...
PMID:Sequential administration of recombinant human interleukin-2 and dacarbazine in metastatic melanoma: a multicenter phase II study. 187 25

The combination of cisplatin plus dacarbazine (DTIC) is active in metastatic melanoma with response rates reported between 10% and 55%. To optimize this regimen, a Phase II study was conducted employing a dose intensity of cisplatin higher than previously reported. Twenty-two patients were treated. Eight patients received cisplatin 100 mg/m2 on days 1 and 8 combined with DTIC 300 mg/m2 on days 1, 2, 8 and 9 (regimen A). Because of excessive toxicity, the protocol was modified so that cisplatin was given at 50 mg/m2 per day and DTIC 350 mg/m2 per day on days 1 through 3 (regimen B). The overall response rate was 32% and consisted of four partial and three complete responses (CR). The median duration of response was 6 months. Two of the CR remain in sustained, unmaintained remission in excess of 1.5 years. All seven patients that responded were treated on regimen B. High-dose cisplatin plus DTIC on a 3-day schedule represents an effective, well-tolerated therapy for metastatic melanoma.
 ...
PMID:High-dose cisplatin plus dacarbazine in the treatment of metastatic melanoma. 200 39

Dacarbazine (DTIC) is an antitumor agent, used for the treatment of metastatic melanoma. It is metabolized to an alkylating agent which reacts with DNA. A fast and simple method was developed in order to measure drug-induced DNA damage in lymphocytes isolated from frozen blood samples of treated patients. The level of DNA damage was determined as single-strand breaks (SSB) by means of the alkaline elution technique using the fluorochrome Hoechst 33258. DTIC induced SSBs in lymphocytes. Most of the DNA damage was repaired after 20 h but after subsequent daily treatments there was an accumulation of SSB. The method described here can be used for monitoring DNA damage in lymphocytes of persons exposed to genotoxic compounds.
 ...
PMID:Induction and time course of DNA single-strand breaks in lymphocytes from patients treated with dacarbazine. 204

Fifty patients suffering from histologically proven metastatic melanoma were treated with a combination of DTIC (400 mg/m2 i.v. every 28 days) and recombinant alpha 2A interferon (Roferon-A) 10 x 10(6) U/m2 daily, administered intramuscularly or subcutaneously for 2 months followed by 7 x 10(6) U/m2 3 times a week. Treatment was carried out for a period of 12 months unless progressive disease was noted after 3 months. Among the 49 evaluable patients, 6 achieved a complete response (CR) and 4 a partial response (PR) (response rate, 20%) at 2 months, 8 CR and 3 PR (25%) and 8 CR and 2 PR (23%; 95% confidence limits, 13-40%) occurred at month 6 and 12 respectively These responses occurred notably in patients with cutaneous (3 cases) or lymph node metastases (4 cases), but 3 responses included visceral sites: lung (1 CR), liver (1CR and 1PR). Average response duration was 16.5 months (range 4-29 + months). The time required for objective response can be up to 6 months, which suggest that treatment should receive a reasonable trial period (at least 3 months). Clinical toxicity consisted mainly of a flu-like syndrome, anorexia and fever, and occurred in more than 50% of patients; hematologic and hepatic toxicities required a dose reduction in 54% of patients but in only one case did treatment have to be terminated because of this. Seventeen (35%) of the patients are still alive, 4 with metastases (follow-up period: 18-34 + months) and 13 without metastases (follow-up period: 13-32 + months). A combined regimen of r-IFN alpha 2A and dacarbazine is effective in treating patients with metastatic melanoma, with acceptable toxicities and a reasonable quality of life (out-patient treatment or district nurse care). The objective response rate (23% at 12 months) compares favourably with those of earlier trials using the same combination of drugs, and occurred not only in cutaneous and lymph node metastases but also in visceral metastases.
 ...
PMID:[Treatment of metastatic melanoma with dacarbazine recombinant interferon alfa 2A combination: results of multicentric study]. 208 Dec 78

Forty-six consecutive, evaluable patients with a diagnosis of metastatic melanoma without prior chemotherapy were treated with bleomycin, vincristine, lomustine, and DTIC (BOLD). Treatment was repeated every 28 days for two cycles. Complete restaging then was performed, and response to treatment was determined. Of the 46 patients, five (11%) achieved a complete response, five (11%) achieved a partial response, nine (19%) obtained disease stabilization, and 27 (59%) had progressive disease. If four patients who died of rapidly progressive disease are included, the response rate drops to 20%. Overall median survival was 6 months. These results are inferior to the 40% and 46% response rates reported by other investigators. The modest response rate toxicity and expense of the regimen do not support its use in metastatic melanoma except, perhaps, in selected patients with soft tissue and/or lung metastasis.
 ...
PMID:Bleomycin, vincristine, lomustine, and DTIC chemotherapy for metastatic melanoma. 245 81


1 2 3 4 5 6 7 8 9 10 Next >>