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)

According to experimental data, administration of interferon in mice before contact with antigen reduced antibody response, while its presence after antigen load enhanced them. The aim of this study was to detect possible immunomodulatory effects of unpurified human alpha-interferon on izohemagglutinin (IZO), and anti-Forssman antibody (AFA) serum levels during a treatment in patients with malignant melanoma. Fifty-two patients treated with the same chemotherapy regimen (ADM-VCR-CPM-DTIC-PCB) entered the study; 30 received INF 1.000.000 U/24 h x 10 during each cycle, intercycle interval 4 weeks. Twenty-two did not receive interferon. Initial IZO titers were 1/4-1/256, median 1/64, and for AFA 0-1/14, median 1/7. Following 4 cycles, values for IZO titers were: in the IFN group 1/32-1/262.144, median 1/128; in the non-IFN group range 1/8-1/512, median 1/32. The values for AFA titers were: in the INF group 0-1/442, median between 1/28 and 1/56; in control group 0-1/112, median 1/14. The difference between both median values for the INF group and initial median values was statistically significant. Initial elevation of titers was reversed during a few cycles with both A and B substances and the Forssman antigen, immunisation of humans is permanent. It would be of interest to ascertain effects of interferons on antibody response to others antigens, especially bacterial and viral, during aggressive chemotherapy. In any case, both experimentally observed phenomena seem to occur in vivo during interferon treatment of metastatic melanoma.
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PMID:[The effect of interferon alfa-2b therapy on titers of isohemagglutinins and anti-Forssman antibodies in patients with malignant melanoma]. 759 Apr 7

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)
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PMID:Chemotherapy and chemoimmunotherapy in disseminated malignant melanoma. 769 93

Total abdominal perfusion (TAP) is a recently described technique in which the abdominal organs are isolated from the systemic circulation and perfused by means of an external pump. Administering chemotherapy into the circuit provides higher locoregional drug exposure with lower systemic toxicity. Two patients with melanoma metastatic to the abdomen were treated using this technique. The first patient suffered from intractable upper gastrointestinal bleeding due to unresectable melanoma metastasis of the duodenum. He underwent TAP with melphalan and cisplatinum. His bleeding stopped and the tumor regressed. The patient's response lasted for 6 months. The second patient had an unresectable liver metastasis. She underwent TAP with melphalan and DTIC, resulting in a complete response with disappearance of the liver mass, which lasted until her death in 13 months. Our conclusion is that TAP should be considered as a technique for regional chemotherapy, which may be used in the treatment of unresectable metastatic melanoma of the abdomen.
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PMID:Total abdominal perfusion (TAP) in the treatment of abdominal metastatic melanoma. 793 65

Metastatic melanoma is difficult to treat because of low response rates to most chemotherapy regimens and short remission durations. Recently, a new chemohormonal regimen containing BCNU, cisplatin, DTIC and tamoxifen (BCDT) has been reported to be more promising. We have treated eight patients with this regimen and five patients responded, including three with complete responses (CR). One of these patients remains in CR beyond two years. Others have also reported response rates of 50% with this regimen with a few long-term remissions also. Two of our patients developed deep venous thromboses (DVT). The increased incidence of DVT with BCDT is attributed to the tamoxifen, which nevertheless appears to be a necessary component of this regimen. In two of our patients, short courses of tamoxifen were used and they both obtained responses (one CR, one PR) without DVT. The possibility of using short-course tamoxifen to reduce the incidence of DVT in this regimen, without impairing its efficacy, should be investigated.
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PMID:The chemohormonal therapy of metastatic melanoma: possible benefit of tamoxifen. 832 61

A single dose of dacarbazine (DTIC), followed by a 5-day intravenous infusion of vindesine (VDS) was administered every 3 weeks to 103 patients with metastatic melanoma. One half of the patients were randomised to receive intravenous methanol extraction residue (MER) of bacillus Calmette-Guerin (BCG) in addition to chemotherapy, on days 7 and 14 of each course. 98 patients were evaluable. The response rates in treatment groups were 16 and 17%, respectively (confidence interval 9-24%). Neither the response rate nor the survival improved when MER was added to chemotherapy. Toxicity was moderate except for a significant granulocytopenia. The combination of DTIC and VDS is not more effective than DTIC alone and has added neurotoxicity.
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PMID:Phase II study of vindesine and dacarbazine with or without non-specific stimulation of the immune system in patients with metastatic melanoma. 847 28

There is increasing experimental evidence to suggest that expression of O6-alkylguanine-DNA-alkyltransferase (ATase) is a major factor in resistance to dacarbazine (DTIC). We recently demonstrated a progressive ATase depletion in human peripheral lymphocytes with nadir levels occurring at 4-6 h after DTIC administration (Lee et al., 1991). Therefore in an attempt to improve the clinical response rate of DTIC, fotemustine was administered 4 h after DTIC administration; since in the case of fotemustine, ATase removes the chloroethyl lesions from the O6-position of guanine, thereby preventing the formation of the cytotoxic cross-links. Sixty patients with widely metastatic melanoma received DTIC at 400, 500 or 800 mg m-2 followed by fotemustine (100 mg m-1) at 4 h after DTIC administration. Treatment was repeated every 28 days with a total of 169 cycles of chemotherapy administered; 75, 57 and 37 treatment cycles with 400, 500 and 800 mg m-2 DTIC groups respectively. Eighteen of the 60 patients responded (with three complete response); response rates were linearly related to dose, being 24%, 30% and 40% in patients receiving 400, 500 and 800 mg m-2 of DTIC respectively and the overall response rate was 30%. Median survival was 3.6 months (range, 1-15 months) with no statistically significant difference between the different DTIC treatment groups (P = 0.67). Nine patients are alive at 5 to 26 months (median 10 months); three patients with no tumour and five patients with stable disease. A statistically significant relationship was seen between the development of severe haematological toxicity (WHO > or = 3) with increasing dosage of DTIC and significant subclinical pulmonary damage was seen in 11 patients where the lung function was monitored during the course of treatment. In conclusion, it appears that with this small group of patients, escalation of DTIC dosage might not significantly affect response rates but does increase haematological toxicity. The present study provides a framework for other studies in an attempt to modulate ATase-mediated drug resistance in tumour tissues but the associated toxicity will need careful monitoring.
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PMID:Sequential administration of varying doses of dacarbazine and fotemustine in advanced malignant melanoma. 851 21

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

Thirty-two patients with metastatic melanoma received combination chemotherapy and hormonal therapy. Treatment included Carmustine, Cisplatin, Dacarbazine and Tamoxifen (BCDT). The overall response rate was 47%: five patients had a complete response (16%), 10 patients had a partial response (31%) and two had no response (6%). The median survival for responders was 10 months (range 2-20). The BCDT regimen was equally effective against soft tissue and visceral metastases. Neither survival or response rate was modified by pretreatment with alpha-interferon (alpha-IFN). In agreement with the results of a recent randomized trial comparing the efficacy of Dacarbazine with that of Dacarbazine plus Tamoxifen, a better survival was found in women than in men: although the response rate was identical (47%), the median duration of response was higher for women. A fall in serum soluble IL-2 receptor (sIL-2R) levels after therapy was seen in responding patients, confirming the usefulness of this parameter in monitoring disease evolution.
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PMID:Therapy for metastatic melanoma: effective combination of dacarbazine, carmustine, cisplatin and tamoxifen. 851 51

A Phase II trial was conducted in patients with metastatic malignant melanoma with DTIC 250 mg/m2 intravenously for 5 days alternating monthly with Piritrexim (PTX) using an intermittent, low-dose oral administration schedule. PTX was administered at a starting dose of 25 mg orally three times per day for 5 days weekly for 3 weeks followed by 1 week of rest. Twenty-one patients were entered into the study. Among the 17 patients assessable for response, 1 patient had a minor response, and 3 patients had stable disease. No partial or complete response were observed. Toxicity was tolerable and consistent mainly of myelosuppression. Using this alternating dose schedule, PTX and DTIC produced little response in metastatic melanoma.
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PMID:Phase II trial of piritrexim and DTIC using an alternating dose schedule in metastatic melanoma. 852 90


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