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)

The combination of dacarbazine (DTIC, 220 mg/m2) and cisplatin (DDP, 25 mg/m2) IV daily for 3 days every 3 weeks, carmustine (BCNU, 150 mg/m2) IV every 6 weeks, and tamoxifen (TAM, 10 mg orally twice daily) produced a 50% objective response rate in patients with metastatic melanoma. Associated with this treatment, there was a high incidence of deep venous thrombosis (DVT) and pulmonary embolism (PE). In an effort to reduce this toxicity, this regimen minus TAM was studied, and the results are reported. Twenty of twenty patients are evaluable for response and toxicity. There was one complete response (CR) lasting 5+ months and one partial response (PR) lasting 4+ months for an overall response rate of 10% (95% confidence limits, 1.23% to 31.70%). Two patients exhibited a mixed response and three patients developed disease stabilization lasting 4 to 10 months. Toxicity was similar to the original study except that no patients developed DVT or PE. This statistically significant (Fisher's exact test [two-tail] P = 0.008) decrease in the response rate by comparison with that achieved with the TAM-containing regimen may signal an essential role of TAM in this regimen. TAM may be acting in synergy with cisplatin through its calcium channel-blocking properties. TAM should be included as described in the initial reports, and the patients should be carefully observed for vascular complications.
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PMID:The importance of tamoxifen to a cisplatin-containing regimen in the treatment of metastatic melanoma. 292 Mar 58

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

The combination of dacarbazine (DTIC), cisplatin (DDP), carmustine and tamoxifen (TAM) has been reported to yield a high rate of response in patients with metastatic melanoma, but responders often experience intracranial recurrences. As fotemustine (FOT) has demonstrated activity on cerebral metastases, the rationale of this study was to replace carmustine by FOT in this four-drug regimen. Twenty patients with metastatic melanoma received FOT (100 mg/m2) on days 1 and 8, DTIC (220 mg/m2 per day) and DDP (25 mg/m2 per day) from day 1 to day 3 and from day 28 to day 30, and continuous daily treatment with TAM (20 mg/day). If stabilization or response was observed at the end of the 8th week, patients received maintenance courses of FOT on day 1, and DTIC (220 mg/m2 per day) and DDP (25 mg/m2 per day) on days 1 to 3. Nineteen patients were evaluable. Of these, six had brain metastases. The overall response rate was 10.5% (two out of 19); both of the responders had only partial responses. The best responding site was lung. No response was obtained in the four patients with evaluable brain metastases, but no patient had therapy failure due to new brain metastases. The median overall survival was 5 months (range 1-45 months). Toxicity was mainly haematological. The use of this combination is not recommended.
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PMID:Combined treatment with dacarbazine, cisplatin, fotemustine and tamoxifen in metastatic malignant melanoma. 961 Aug 72

This randomized phase II trial was performed to define the activity and toxicity of the combination of dacarbazine (DTIC), carmustine (BCNU), cisplatin (DDP) and tamoxifen (DBDT regimen) versus DTIC alone in patients with metastatic melanoma. Sixty patients with metastatic melanoma were randomly assigned to receive BCNU 150 mg/m2 intravenously (i.v.) on day 1, cisplatin 25 mg/m2 i.v. daily on days 1 to 3, DTIC 220 mg/m2 i.v. daily on days 1 to 3 and tamoxifen 160 mg orally daily for 7 days prior to chemotherapy (DBDT arm; arm A). Treatment cycles were repeated every 28 days, while BCNU was given every two cycles. The DTIC arm (arm B) patients received DTIC alone 1200 mg/m2 i.v. on day 1, repeated every 21 days. Patients were evaluated every two cycles; responding patients continued the treatment for a maximum of 12 cycles. The overall response rate was 26% in the DBDT arm and 5% in the DTIC arm. Complete responses were 2.5% for DBDT and 0% for DTIC. The median progression-free survival and the median survival were 4 and 9 months, respectively for DBDT, and 2 and 7 months for DTIC. DBDT was associated with significant haematological toxicity: 33% of the patients experienced a grade III or IV neutropenia and 28% a grade III or IV thrombocytopenia. In conclusion, the overall response rate obtained with DBDT was greater than that obtained with DTIC alone; however, this combination increases toxicity with limited impact on overall survival.
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PMID:Phase II randomized study of dacarbazine, carmustine, cisplatin and tamoxifen versus dacarbazine alone in advanced melanoma patients. 1133 30