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)

Human malignant melanoma was transplanted to the cheek pouch of immunosuppressed (corticosteroid-treated) hamsters. Significant differences were observed in tumor growth constants for animals treated with methotrexate, DTIC, BCNU, and vincristine (P < 0.05) compared to controls. However, no appreciable effect was demonstrated for Adriamycin, 5-FU, and cytoxan. In addition, single doses as high as 400 mg/kg body weight of methotrexate were no more effective than other agents now used against this neoplasm.
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PMID:Chemotherapy against human melanoma in the hamster cheek pouch. 745 85

A study was undertaken to investigate the addition of heparin and pseudomonas vaccine to BCNU in the treatment of patients with progressive malignant melanoma refractory to front-line therapeutic regimens containing DTIC. Out of 27 evaluable patients, there was one partial remission (4%), and an additional ten patients (41%) had at least stable disease with a median survival time of 39 weeks compared to 15 weeks for those with progressive disease. The therapy was well tolerated. A schedule of pseudomonas vaccine that seemed to be tolerated has been established.
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PMID:Combination therapy for advanced malignant melanoma with BCNU, pseudomonas vaccine, and heparin. 746 50

Since cytotoxic chemotherapy (BCNU, DTIC and cisplatin, tamoxifen) and interferon-alpha (IFN-alpha) have each produced responses in advanced malignant melanoma, a phase II trial was conducted to evaluate the response and toxicity of simultaneous administration of both therapies. Of 33 assessable patients, two (6%) had complete response (CR) and 12 patients (36%) had partial response (PR), for a total response rate (CR+PR) of 42% (95% confidence interval 26-58). Four patients had minor response (12%). Mixed responses occurred in five patients (15%). The remaining patients had progressive disease. The duration of CR was 3, 7 and 17 (+) months and the duration of PR was 3+ to 19+ months (median 6 months). The median overall survival for all patients entered into the study was 5 months. Main toxicities included myelosuppression and fatigue. Combined simultaneous cytotoxic chemotherapy and IFN produced a high response rate (42%) which is comparable to that reported for chemotherapy alone. Further studies are needed to determine the optimal schedule for combining chemotherapy and immunotherapeutic agents as well as the impact of biological agents on survival in the treatment of melanoma.
Melanoma Res 1995 Aug
PMID:Phase II trial of recombinant interferon-alpha with BCNU, cisplatin, DTIC and tamoxifen in advanced malignant melanoma. 749 64

Malignant melanoma, once disseminated, is associated with very short survival times and has proven highly resistant to systemic therapy. Although many chemotherapeutic agents can produce small response rates in these patients, the most consistent responses occur with dacarbazine (DTIC). Numerous combination regimens, with and without DTIC, have been tested against disseminated melanoma, with varying and inconsistent outcomes. The most encouraging results have occurred with the combination of DTIC, cisplatin, BCNU and tamoxifen. The use of high-dose chemotherapy with and without autologous bone marrow support and the addition of biologic agents such as inteferon-alpha and interleukin-2 to conventional chemotherapy have also been actively investigated. This paper reviews the various approaches taken against disseminated melanoma employing systemic chemotherapy.
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PMID:Combination chemotherapy for disseminated malignant melanoma. 757 52

Both chemotherapy and interleukin-2 and/or interferon-alpha produce objective responses in a proportion of advanced malignant melanoma patients. While duration of response to chemotherapy is short, i.e. usually below 4 months, immunotherapy has resulted in a small number of long-lasting remissions in patients with metastatic melanoma. In two consecutive phase II trials in a total of 67 patients, we assessed the potential synergism between both modalities, i.e. chemo- and immunotherapy. Treatment consisted of intravenous (i.v.) carboplatin (CBDCA, 400 mg/m2) and dacarbazine (DTIC, 750 mg/m2) given twice (i.v. bolus over 30 min) at 3-week intervals, or 4 cycles of DTIC (220 mg/m2 i.v. 3 days), cisplatin (DDP, 35 mg/m2 i.v. 3 days), carmustine (BCNU, 150 mg/m2 i.v. cycles 1 and 3) and tamoxifen (TAM, 20 mg oral/daily) at 3-week intervals. Chemotherapy was followed by immunotherapy with combined subcutaneous (s.c.) interleukin-2 (rIL-2) and SC interferon-alpha 2 (rIFN-alpha). Among 40 patients who received a full cycle of chemotherapy with CBDCA/DTIC and sequential immunotherapy, there were 3 (7.5%) complete remissions (CRs) with a median duration of 19 months (range 13-26+). Partial remissions (PRs) were noted in 11 (27.5%) patients with a median response duration of 8 (range 5-14) months. Among 27 patients who received DTIC/DDP/BCNU/TAM and rIL-2/rIFN-alpha, there were 3 (11%) complete remissions and 12 (44.5%) partial remissions. Duration of complete and partial remissions ranged from 9+ to 13+ (median, 11+), and 5 to 15+ (median, 7+) months, respectively. Chemotherapy produced mostly moderate toxicity. Thrombocytopenia was common with the nadir after a median time of 18 days following start of CBDCA/DTIC and DTIC/DDP/BCNU, respectively. 10 patients required transfusion of thrombocytes. Nausea and vomiting due to chemotherapy were well tolerated using concomitant ondansetrone (8 mg i.v.). Immunotherapy was self-administered at home with mild to moderate side effects; malaise, fever, chills, nausea/vomiting, diarrhoea, anorexia and arthralgias were most frequent, but were spontaneously reversible after ending rIL-2/IFN-alpha. A mean 87 and 88% of the projected doses of rIL-2 and rIFN-alpha were administered on either protocol. There were no life-threatening complications and no treatment-related deaths. The sequential combination of chemotherapy and rIL-2 plus rIFN-alpha had at least additive therapeutic activity against metastatic malignant melanoma. The schedules produced long-lasting remissions and were tolerated well overall. These trials substantiate a potential role for low to intermediate dose immunotherapy in maintaining and consolidating therapeutic effects of chemotherapy in metastatic melanoma.
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PMID:Chemoimmunotherapy of advanced malignant melanoma: sequential administration of subcutaneous interleukin-2 and interferon-alpha after intravenous dacarbazine and carboplatin or intravenous dacarbazine, cisplatin, carmustine and tamoxifen. 764 14

Treatment of metastatic melanoma with cytotoxic drugs is still associated with low response rates and high toxicity. The most effective single agents in metastatic melanoma produce response rates between 15 and 20%. Combined schedules based on dacarbazine (DTIC), carmustine (BCNU), cisplatin and vinca alkaloids produced objective response rates between 25% and more than 40%; adverse effects, however, were severe and prolongation of survival remains uncertain. Cytokines were therefore introduced as melanoma treatment, with initial high expectations. Interferon (IFN)-alpha as a single treatment produced an overall response rate of 10-15% in melanoma patients. Clinical and experimental results suggest that the antitumour activity of IFN is mainly related to its antiproliferative effect; immunomodulatory effects were not substantiated in clinical investigations. Adoptive immunotherapy of metastatic melanoma has been established by use of lymphokine-activated killer (LAK) cells plus interleukin-2 (IL-2) or high dose IL-2 alone. Clinical trials of adoptive immunotherapy showed objective response rates of 20-25% in disseminated melanoma, and response rates could be further improved by the combination of IL-2 with IFN-alpha. Clinical trials with combined IFN or/and IL-2 and cytostatic drug therapy started a few years ago and have yielded promising initial results. The combination of IFN-alpha with dacarbazine was effective in over 50% of treated patients, leading to complete or partial remissions in 28% and stabilization of the disease in an additional 28% of more than 400 patients treated so far. Recently, a new generation of multidrug combinations including IFN-alpha and/or IL-2 has been initiated with overall response rates of more than 50% in several reports.(ABSTRACT TRUNCATED AT 250 WORDS)
Melanoma Res 1993 Aug
PMID:Chemotherapy and chemoimmunotherapy in disseminated malignant melanoma. 769 93

Intoplicine (RP 60475, NSC 645008) is a new 7H-benzo[e]pyrido [4,3-b] indole derivative which interacts with DNA and inhibits both topoisomerases I and II. In vitro it was found cytotoxic against various cell types with greater cytotoxicity towards solid tumor cells. We report here the anticancer activity of RP 60475 against a variety of transplantable tumors of mice, and also its cross-resistance profile in leukemias. The end points used were % T/C (median tumor weight of the Treated over the Control x 100) and logCK (log10 cell kill total). RP 60475 administered i.v. was found schedule-independent with a peak plasma level problem. It had a good therapeutic index and host recovery usually occurred 7.5 days post last treatment. RP 60475 was found to be highly active against early stage colon 38 (T/C = 0%, 2.9 logCK) and could induce 5/5 complete regressions of advanced stage tumor. It was found active against colon adenocarcinoma 51 (T/C = 3.6%, 1.9 logCK) and colon carcinoma 26 (T/C = 11.7%, 1.2 logCK). Most of the mammary adenocarcinomas were found very responsive, MA16/C (T/C = 0%, 2.8 logCK), MA14/A (T/C = 0%, 1.4 logCK), MA13/C (T/C = 0%, 3.1 log CK) and MA44 (T/C = 34%). Excellent activity was also observed against early stage pancreatic ductal adenocarcinoma 03 (T/C = 0%) and RP 60475 could achieve 5/5 complete regressions of upstaged tumor. Activity was also obtained on Glasgow osteogenic sarcoma (T/C = 0%, 3.3 logCK), on B16 melanoma (T/C = 14%, 1.3 logCK) and to a lesser extent on Lewis lung carcinoma (T/C = 33.2%). Evaluation of RP 60475 against leukemia sublines with acquired resistance, revealed that L1210/cisplatin and L1210/BCNU were not cross-resistant to RP 60475 whereas P388/vincristine was partially cross-resistant to RP 60475 and P388/doxorubicin was cross-resistant to RP 60475. Based on RP 60475 broad activity against transplantable tumors of mice, its effectiveness against some resistant sublines, its original mechanism of action and its acceptable toxicological profile, this compound was selected for clinical trials.
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PMID:Antitumor activity of intoplicine (RP 60475, NSC 645008), a new benzo-pyrido-indole: evaluation against solid tumors and leukemias in mice. 815 69

173 patients with regional lymphatic metastases (n = 139) or distant disease (n = 34) were prospectively randomised, following resection of all clinically detectable tumour, to observation (n = 88) or adjuvant chemotherapy (n = 85). The treatment group received 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) 80 mg/m2 intravenously (i.v.) every 4 weeks, and actinomycin-D 10 micrograms/kg, vincristine 1.0 mg/m2 i.v. every 2 weeks for 6 months. The disease-free survival curves between the two groups were significantly different (P = 0.03). The estimated 5-year disease-free survival rate for the observation group was 9% and for the treatment group 29%. However, the overall survival curves were not significantly different for the two groups. Nitrosoureas may have a weak effect as adjuvant treatment in malignant melanoma.
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PMID:Adjuvant chemotherapy with a nitrosourea-based protocol in advanced malignant melanoma. 826 Feb 35

Cell lines resistant to five antitumor alkylating agents (CDDP, PAM, 4-HC, HN2, and BCNU) were developed from five parental human tumor lines representative of solid tumors with a range of sensitivities to antitumor alkylating agents. The parental cell lines were SCC-25 squamous carcinoma of the head and neck, MCF-7 breast carcinoma, SW2 small-cell lung cancer, SL6 non-small-cell lung carcinoma, and G3361 melanoma. Survival curves using colony formation as the endpoint were generated for each of the 25 cell lines to each of the five alkylating agents. Comparison of the drug concentrations that reduced the survival of the alkylating agent-resistant cell lines by 90% (IC90 values) with the IC90 values obtained for the corresponding parental cell lines was used as a measure of the resistance/sensitivity of the alkylating agent-resistant lines to each drug tested. Although cross-resistance among the alkylating agents was generally uncommon, several patterns of response emerged. Cross-resistance occurred in 27 of the 105 determinations and occurred most frequently in the cell lines in which resistance was developed to PAM (57%) or BCNU (38%). Cross-resistance to HN2 occurred most frequently. Collateral sensitivity was equally as common, occurring in 25 of the 105 determinations. Collateral sensitivity occurred most frequently in the cell lines made resistant to 4-HC. The 4-HC-resistant cell lines were most frequently collaterally sensitive to PAM and to BCNU. Cross-resistance developed most frequently in the MCF-7 breast carcinoma and SCC-25 squamous-cell carcinoma cell lines, whereas collateral sensitivity developed most frequently in the SW2 small-cell lung cancer line and the G3361 melanoma cell line and least frequently in the MCF-7 breast carcinoma cell line and the SL6 non-small-cell lung cancer cell line. The implication of these findings for the development of strategies for clinical treatment are discussed.
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PMID:Antitumor alkylating agents: in vitro cross-resistance and collateral sensitivity studies. 826 70

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


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