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

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

WR-2721 is an aminothiol compound; in the animal model it protects against the nephrotoxicity, neurotoxicity, and hematologic toxicity of cis-platinum. We initiated Phase I trials of WR-2721 and cis-platinum to determine toxicity when WR-2721 was given prior to escalating doses of cis-platinum. With mannitol diuresis and WR-2721, transient nephrotoxicity occurred in 9 of 30 (27%) patients treated with cis-platinum 150 mg/m2 and 7% of patients given with cis-platinum 120 mg/m2. Bone marrow suppression was mild and infrequent. Mild to moderate peripheral neuropathies occurred in 26% of patients courses following a mean cumulative cis-platinum dose of 725 mg/m2. Objective partial responses were observed in 53 of 118 (45%) patients with measurable disease. Antitumor responses were observed in 25 of 53 patients with metastatic melanoma, 12 of 22 patients with locally recurrent or metastatic head and neck cancer, and 7 of 13 patients with metastatic breast cancer refractory to conventional chemotherapy. Controlled studies of WR-2721 and cis-platinum will be performed in the Eastern Cooperative Oncology Group in these disease sites to better define the activity of this regimen and its toxicity.
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PMID:Clinical trials of WR-2721 and cis-platinum. 254 Nov 21

The Central Pennsylvania Oncology Group conducted a phase II study of mitolactol in advanced metastatic melanoma to determine the overall survival rate and duration of response to this agent. The starting dose was 100 mg/m2/day orally. If no hematologic toxicity was noted on weekly blood cell counts, the dose was increased to 130 mg/m2/day on Day 35, and, if still tolerated, to 160 mg/m2/day on Day 70. Six of 25 evaluable patients (24%) had objective partial response. The median duration of response was 20 weeks, with a range of 10-66 weeks. Six of 25 patients (24%) had stable measurable disease, with a median duration of 9 weeks. The median survival from date of entry in this study was 21 weeks in responding or stable patients compared to 7 weeks in nonresponders. Hematologic toxicity was the dose-limiting factor. This study shows that mitolactol has moderate activity against advanced melanoma, and the drug deserves further study in combination with nonmyelotoxic drugs.
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PMID:Phase II study of mitolactol in metastatic malignant melanoma. 396 60

A phase I clinical trial of N-phosphonacetyl-L-aspartic acid (PALA) and 5-fluorouracil (FUra) was performed on 30 patients. PALA was given as a 15-minute iv infusion once daily for 5 days, and FUra was given as a bolus injection on days 2, 3, 4, and 5. Cycles of treatment were repeated every 3 weeks. Dose-limiting toxicity was manifested by stomatitis and diarrhea. Skin rash was observed also but was not dose limiting. No consistent hematopoietic or renal toxicity was observed. Seventeen patients with disseminated metastatic melanoma and measurable disease were evaluated for response. One partial response was seen; however, the response was associated with significant toxicity, and the treatment could not be repeated. Stable disease was observed in 3 patients with melanoma, 1 patient with colon carcinoma, and 1 patient with ovarian carcinoma. Our findings suggest that the clinical activity of PALA and FUra given according to the above schedule for melanoma is less than 25% (P less than 0.05). Pharmacokinetic studies of FUra revealed no consistent effect of PALA pretreatment on FUra disappearance in plasma. The mean FUra elimination half-line in plasma was 7.11 +/- 0.84 minutes (SEM), which is no different from that reported for FUra alone. The recommended doses on this schedule for phase II studies are 1,000 mg PALA/m2/day iv daily for 5 days and 200 mg FUra/m2/day iv on days 2, 3, 4, and 5.
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PMID:Phase I-phase II trial of N-phosphonacetyl-L-aspartic acid given by intravenous infusion and 5-fluorouracil given by bolus injection. 695 Jan 56

The management of metastatic melanoma has been frustrating from a clinician's point of view because of the relative unresponsiveness of the tumor to chemotherapy and the infrequency of clinically useful objective responses. Although no single agent can be recommended at this time, old standard drugs used in new combinations, immunomodulators, and systematic approaches to dose intensification have created more interest in the chemotherapy of melanoma. Forty-seven consecutive patients with Stage 4 melanoma with measurable disease were treated with combination chemotherapy, consisting of DTIC, BCNU, cisplatin, and tamoxifen. The cycle was repeated every 4 weeks and a total of 6 cycles were delivered. Patients were then restaged to assess the response. Nine patients who were registered during the same time period with Stage 4 disease and elected not to be treated served as the control population. Seventeen patients (46%) achieved a clinical response with six patients (12.7%) undergoing a complete response. The overall survival of all Stage 4 patients in the series was 18% at 3 years. There were significant differences noted in those patients who were treated and the no treatment controls (p = 0.004) and for those patients that received an objective response vs those that progressed on the protocol (p < 0.0001). It is recommended that all patients with Stage 4 melanoma be treated on protocol and results of other trials of systemic therapy for metastatic melanoma be compared to this cisplatin-based regimen instead of a no-treatment arm.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chemotherapy for stage 4 melanoma: a three-year experience with cisplatin, DTIC, BCNU, and tamoxifen. 851 13

This is a preliminary report on the efficacy and toxicity of the combination chemotherapy regimen with carboplatin and cytosine arabinoside in dacarbazine-resistant metastatic melanoma. Patients were considered eligible in the presence of measurable disease sites, an ECOG performance status of 2 or less, a life expectancy of at least 2 months, and prior dacarbazine treatment. The planned schedule consisted of cytosine arabinoside (150 mg/m2 intravenously plus 50 mg subcutaneously), followed by a rapid infusion of carboplatin (350 mg/m2 on day 1). Courses were administered every 3 weeks according to hematologic recovery. Twenty-one consecutive patients were evaluable for activity and toxicity, the response rate was 19% (95% confidence interval, 5-42%). There was no complete remission. Toxicity was tolerable being myelosuppression the main side effect. In conclusion, the combination of carboplatin and cytosine arabinoside has limited activity as a salvage treatment in melanoma patients failing on dacarbazine chemotherapy. Moreover, the regimen is well tolerated and easy to administer in an outpatient setting.
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PMID:Combined carboplatin and cytosine arabinoside in metastatic melanoma refractory to dacarbazine. 854 Jan 18

An open, multicentre non-randomised study was performed to evaluate the activity and toxicity of combination chemoimmunotherapy, consisting of cisplatin, interleukin-2 and interferon-alpha, in metastatic malignant melanoma. Between March 1992 and September 1993, 28 patients with pathologically proven metastatic malignant melanoma, bidimensionally measurable disease and an Eastern Co-operative Oncology Group score < or = 1 were treated with the combination chemoimmunotherapy. The regimen consisted of cisplatin (100 mg/m2 on day 0), interleukin-2 (Proleukin, Chiron, Middlesex, U.K.) 18 x 10(6)IU/m2/d continuous intravenous infusion on days 3-7 and 17-22, with interferon-alpha (Roferon-A, Roche, Hertfordshire, U.K.) 9 x 10(6) U/d subcutaneously on days 3, 5, 7, 17, 19, 21 during the interleukin-2 infusions. The treatment cycle lasted 28 days. Among 27 assessable patients, 5 patients achieved partial responses, for an overall response rate of 18% (95% CI 6-37%). Median progression-free survival was 44 days (range 8-279) and median overall survival was 264 days (range 41-1432). Differential responses were noted in 41% of patients and responses were more frequent in non-visceral disease (skin, lymph node and soft tissue disease) (P = 0.04). These results indicate that differential responses to chemoimmunotherapy are common in patients with metastatic melanoma. This may account for the broad range of response rates reported in the literature.
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PMID:Differential responses to chemoimmunotherapy in patients with metastatic malignant melanoma. 933 79

Our objective was to determine the clinical activity, toxicity, and immunological effects of active immunotherapy using UVB-irradiated (UVR) autologous tumor (AT) cells plus adjuvant DETOX in metastatic melanoma patients. Eligibility included nonanergic patients fully recovered after resection of 5 or more grams of metastatic melanoma. Treatment consisted of intradermal injections of 10(7) UVR-AT plus 0.25 ml of DETOX every 2 weeks x 6, then monthly. Peripheral blood mononuclear cells (PBMCs) were harvested for cytotoxicity assays, and skin testing was performed for delayed-type hypersensitivity (DTH) determinations before the first, fourth, seventh, and subsequent treatments. Forty-two patients were treated, 18 in the adjuvant setting and 24 with measurable disease. Among the latter group, there were two durable responses in soft-tissue sites and in a bone metastasis. Treatment was well tolerated. Thirty-five patients were assessable for immunological parameters; 10 of these patients, including the 2 responders, demonstrated early induction of PBMC cytotoxicity against AT cells that persisted up to 10 months on treatment before falling to background levels. In five of seven patients, the fall-off heralded progressive disease. Late induction of a weak DTH reaction to AT cells was observed in eight patients. Active immunotherapy with UVR-AT + DETOX had modest but definite clinical activity in advanced melanoma. The induction of both PBMC cytotoxicity and DTH reactivity to AT cells supported a specific systemic immune effect of treatment, although the former more closely followed disease course in this study.
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PMID:Active immunotherapy with ultraviolet B-irradiated autologous whole melanoma cells plus DETOX in patients with metastatic melanoma. 953 29

Heat shock proteins have been the focus of many experimental studies during the last few years in order to understand their biology and their imunologic features. We conducted pre-clinical experiments showing that gp96 purified from human melanoma lines can represent melanoma antigens and stimulate T cells known to recognize such antigens. Clinical studies of vaccination were then initiated by our group by using heat-shock protein gp96 purified from autologous tumor tissues in patients with melanoma and colorectal carcinoma. The results of these trials in metastatic melanoma patients with measurable disease showed that a melanoma-specific T cell response can be generated or increased in approximately 50% of vaccinated patients. Moreover, signs of clinical responses were obtained consisting of two complete responses and three long-lasting stabilizations. Similar results were obtained in patients with liver metastases of colorectal cancer made disease-free by surgery. In both studies a clear association was found between T cell immune response induced by the vaccine and clinical response both in the trial of melanoma (tumor response) and in that of colorectal cancer patients (disease-free and overall survival at 5 years).
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PMID:Heat shock proteins gp96 as immunogens in cancer patients. 1675 42

Serum levels of S100B and/or lactate dehydrogenase (LDH) are putative tumor markers in melanoma. Early changes in such markers may correlate with a positive immune response to vaccine therapy. In patients with metastatic melanoma, S100B and LDH serum levels were measured at baseline, and 1 week after 3 weekly subcutaneous injections of investigational, patient-specific vaccines consisting of autologous dendritic cells loaded with antigens from irradiated proliferating autologous tumor cells, and suspended in granulocyte macrophage colony-stimulating factor. There was a poor correlation between S100B and LDH levels at baseline (p = 0.324). Fourteen (14) patients with measurable disease had higher S100B (p = 0.0456) and LDH (p = 0.0013) levels than 31 patients who lacked measurable disease at that time. Fourteen (14) deceased patients (median survival, 13 months) had a mean baseline S100B of 0.62 mug/L (95% confidence interval [CI] 0.00-1.66) and LDH of 815 U/L (95% CI 222-1408); 31 surviving patients (median follow-up, 35.4 months) had mean S100B of 0.07 mug/L (95% CI 0.00-0.23; p = 0.006) and LDH of 442 U/L (95% CI 296-588; p = 0.002). Elevated baseline levels of LDH and S100B were each predictive of inferior progression-free survival (PFS) and overall survival (OS) (both p < 0.0001), but S100B was a better predictor for PFS than LDH. Changes in LDH between baseline and week 4 were not predictive of survival, but an increase in S100B predicted for inferior OS ( p = 0.039). Both LDH and S100B are predictive tumor markers in patients with metastatic melanoma. This is the first study to examine the changes in serum levels of LDH and S100B in response to an autologous tumor-cell vaccine.
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PMID:Lack of elevation of serum S100B in patients with metastatic melanoma as a predictor of outcome after induction with an autologous vaccine of proliferating tumor cells and dendritic cells. 1845 90


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