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)

The treatment of patients with metastatic melanoma remains a difficult problem. It is clear that more effective agents need to be developed. No single agent in conventional doses has been shown to be more effective than DTIC alone. The results obtained with detrorubicin in untreated patients are encouraging, but need further confirmation. If confirmed, combination regimens incorporating detrorubicin should be studied. Further experience is needed with high-dose cisplatin before it can be recommended for broader clinical use. Recent experience with the 4 drug combination of DTIC, BCNU, cisplatin, and tamoxifen is encouraging. The objective response rate is approximately 50% and patients with visceral disease have demonstrated regressions. CRs are not uncommon with occasional patients exhibiting durable remissions for as long as 3 years. An added benefit is that this regimen is well tolerated by most patients making it technically easy to administer. Finally, the role of interferon needs further study. The response rate to interferon alfa-2a is reasonably well defined at about 20%. Combinations of chemotherapeutic agents and interferons have only begun to be evaluated but the preliminary data are interesting.
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PMID:Systemic chemotherapy for metastatic melanoma. 246 47

The majority of patients with stage I melanoma can be cured with surgery. Extension of tumor to the regional lymph nodes portends a poor prognosis, with an expected 5-year survival rate of no more than 20% to 25%. Adjuvant therapy has not been particularly useful in such patients. Patients with metastatic melanoma generally do poorly and have a median survival of 4 to 6 months. Such patients are treated with systemic therapy unless they have a surgically resectable single site of metastasis, in which case surgical resection offers the best palliation. The chemotherapeutic agent that is most widely used is dacarbazine (DTIC), which has been in use for the past 20 years. When used as a single agent, DTIC has produced response rates of 15% to 20%. These responses largely occur in soft-tissue disease and last an average of 3 to 6 months. Complete remissions occur in fewer than 5% of patients. In addition to DTIC, other drugs with significant activity against metastatic melanoma are the nitrosoureas, the vinca alkaloids, and cisplatin. Combinations of DTIC and nitrosoureas have not resulted in significant improvement in the response rate, which has generally been 20% to 25%. During the past decade, several triple-drug combinations have been tested, with some evidence of an increase in the response rate to 25% to 30%. More recently developed combinations incorporating cisplatin and the vinca alkaloids in conjunction with DTIC have yielded response rates of 30% to 40%. Because most of these reports are pilot studies and have not been tested in controlled trials, the evidence of the superiority of these combined regimens over DTIC alone cannot be considered conclusive. Combination chemotherapy regimens do produce slightly higher complete response rates of approximately 10%, and the duration of responses is somewhat longer (6 to 9 months). During the past 5 years, biologic therapy with interferons and interleukin-2 (IL-2) has shown clinical evidence of activity against metastatic melanoma. The recombinant alpha interferons (alfa-2a and alfa-2b) have been widely used and have induced tumor regressions in 15% to 20% of patients. Because the activity of interferons is not compromised by prior chemotherapy, their use is more popular as second-line therapy, with an expected overall response rate of 15%. Other studies have utilized interferon in untreated patients, where the response rate may be slightly higher.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Current therapy for malignant melanoma. 246 75

Twenty-four evaluable patients with metastatic melanoma have been entered in a multicentre Phase II study of two induction cycles of human recombinant interleukin-2 (rIL-2) 18 x 10(6) IU/m2/day continuous i.v. bolus on days 1-5 and days 12-17. Dacarbazine (DTIC) 850 mg/m2 i.v. bolus was given on day 26. The cycle was repeated at five weeks. Maintenance therapy was scheduled three weeks after the completion of the induction treatment, consisting of rIL-2 18 x 10(6) IU/m2/day for five days alternating with DTIC 850 mg/m2 i.v., every three weeks, for a total of 18 weeks. Median age was 44 years (range 23-80), and Karnofsky index was 100 (range 80-100). One patient had received prior chemotherapy with hydroxyurea and one patient had prior radiotherapy. Six patients responded (25%): two had complete responses (CR) and four had partial responses (PR). Stable disease (SD) was seen in five patients. Responses occurred in the following sites: liver 2/9 (22%), lung 3/14 (21%), skin 2/11 (18%), and lymph nodes 3/12 (25%). Duration of CR was 11+ and 13 months. PRs lasted 2, 5, 7, and 11+ months. Of note, time to progression in patients with SD was similar to that of responders: 4, 4, 11+, 11+, and 14+ months. Toxicity included fever, skin rash, fatigue, anorexia, and diarrhoea in most patients. Two patients had a weight gain of more than 10%. Hypotension requiring vasoactive agents or interruption of rIL-2 occurred in four patients, creatinine elevations WHO grade 1-2 in seven patients, and bilirubin elevations WHO grade 1-3 in six patients. One patient developed transient ventricular tachycardia. It appears that rIL-2 and DTIC in this schedule is feasible and effective, but not clearly superior to rIL-2 alone.
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PMID:Sequential administration of recombinant human interleukin-2 and dacarbazine in metastatic melanoma. A multicentre phase II study. 269 78

Between April 1988 and August 1989, 30 melanoma patients were entered in a multicentre Phase II study of dacarbazine (DTIC) 850 mg/m2 i.v. bolus on day 1, and recombinant interleukin-2 (rIL-2) (Cetus) 18 x 10(6) IU/m2/day i.v. continuous infusion on days 4-9. Six treatment cycles were given: the first two at an interval of 13 days, and further cycles at intervals of 20 days. Twenty patients are currently evaluable for toxicity and 18 for response. Two of these patients presented with metastatic intraocular melanoma. Median age was 48 years (range 18-83), and median Karnofsky index was 100 (range 80-100). Four patients had received prior radiotherapy and one had received prior immunotherapy. Seventeen patients received two cycles of treatment and nine patients received three or more cycles. Four patients responded (22%): two complete remissions and two partial remissions. Stable disease was seen in six patients (33%). Responses occurred in the lung, skin, spleen and lymph nodes. Seventy-five percent of the patients received the full dose of rIL-2 during cycle 1, whilst only 2 out of 9 (22%) received the planned dose on the third cycle. Rebound lymphocytosis of 5.3 x 10(3)/L (range 1.2-18.1) occurred 24-48 h after rIL-2, but was not predictive for response. Currently, there is no evidence that pretreatment with DTIC impacts negatively on the rIL-2-stimulated lymphocyte proliferation. The toxicity profile of this treatment regimen did not differ significantly from that already described for similar regimens of rIL-2. However, in this interim analysis, there was a trend for a higher percentage of patients (25%) to experience severe weight gain (greater than 10%). This study shows that this treatment regimen is active in metastatic melanoma, with acceptable toxicity. Further research will focus on using other chemotherapeutic agents and/or other biological response modifiers (e.g. interferons, tumour necrosis factor) in combination with rIL-2.
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PMID:Sequential dacarbazine chemotherapy followed by recombinant interleukin-2 in metastatic melanoma. A pilot multicentre phase I-II study. 269 79

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

The combination of recombinant human interferon alpha A 9 MU daily intramuscularly and etretinate 50 mg daily orally was given to 25 patients with progressive advanced, metastatic melanoma. The treatment was well tolerated. Partial responses were seen in three (12%) patients lasting from 2 to 8 months. A further partial response was seen in one of three patients when they were given vindesine and DTIC whilst they continued receiving interferon and etretinate.
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PMID:Treatment of advanced malignant melanoma with interferon alpha and etretinate. 338 79

A randomized phase II study of AMSA (amsacrine) alone and AMSA combined with DTIC (dacarbazine) was carried out in 31 and 39 patients with metastatic melanoma respectively. AMSA was used at a starting dose of 40 mg/m2/day X 3 days with escalation to 50-60 mg/m2/day X 3 days in 8 pts. For AMSA + DTIC the starting dose was: AMSA 30 mg/m2/day X 3 days; DTIC, 800 mg/m2 X 1 day. Additionally, seven pts received AMSA in a similar dose schedule but DTIC was used in a 5-day schedule of 250 mg/m2/day. Twenty-five patients were evaluable for response in the AMSA group and 36 in the AMSA + DTIC group. The objective response to AMSA included 1(4%) partial response compared with 11 complete or partial responses (30%) with AMSA + DTIC therapy. The median lowest absolute granulocyte count was 1100/microliters in AMSA group compared with 1000/microliters in the AMSA + DTIC group. Severe neutropenia of less than 500 granulocytes/microliter was observed in 5 pts in the AMSA group compared with 13 pts in the AMSA + DTIC group. We concluded that AMSA has no significant activity against melanoma, although the combination of AMSA + DTIC seemed to be more active than DTIC alone.
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PMID:Phase II study of AMSA alone and in combination with DTIC in patients with metastatic melanoma. 341 Jun 67

Forty-three patients with widely metastatic melanoma were studied. Visceral metastases were present in 79% of the patient group, including five patients with brain metastases. No patients were excluded because of "early death," etc., from analysis. All 43 patients received 24-hour DTIC infusions. Dosages for individual patients ranged from 350 mg/M2 to 2.5 g/M2, a maximum of 6 courses being given. A total of 155 courses was administered. Hemibody irradiation (HBI) was delivered after 1 or 3 courses of DTIC to the area of maximum disease in 23 patients. Fourteen of the 43 patients responded to DTIC chemotherapy (with one complete response), a response rate of 33%. Seven of the chemotherapy responders also responded in other sites to subsequent HBI, a response rate of 30% (7/23). No patient responded to HBI and not to DTIC. Median survival was 4 months (range, 1-15), and nine patients are still alive at 3 to 15 months. Toxicity was generally mild, although there was one possible treatment-related death. Further exploration of DTIC infusion chemotherapy and HBI would be of interest.
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PMID:Treatment of metastatic melanoma by 24-hour DTIC infusions and hemibody irradiation. 369 10

Dacarbazine has shown the most consistent activity of any single chemotherapeutic agent in patients with metastatic melanoma. While the overall rate is 21%, responses fall to less than 10% when hepatic metastases are present. We report a patient with malignant melanoma metastatic to the liver in whom an apparent dose-response relationship to dacarbazine was demonstrated. His liver metastases responded to hepatic artery infusion, progressed with systemic iv therapy, and responded upon reinstitution of hepatic artery infusion.
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PMID:Dose-response relationship to dacarbazine demonstrated in a patient with malignant melanoma. 375 41

Seventy-nine patients with Stage III widely metastatic melanoma were prospectively randomised to a 'no treatment' control group who received on tumour progression DTIC (250 mg/m2 i.v. daily X 5) and Actinomycin D 1.5 mg/m2 on Day 1. A total of six courses at 3-week intervals was given. Chemotherapy was only given on progression of disease. The other group received initially Corynebacterium parvum (2 mg/m2) every 3 weeks for a maximum of eight courses and then the same chemotherapy on evidence of progressive disease. Minimum follow up time is 3 yr. The chemotherapy response rate (control 37%, C. parvum 24%) was not statistically different nor was the effect of chemotherapy on the site of individual metastases. Radiotherapy responses for irradiated soft tissue disease again were not significantly different, between the two patient groups. No significant differences in survival (control group median, 4 months, range 1-46; C. parvum median 3 months range 1-35) were observed and only one patient is alive at 35 months. The pattern of relapse was also similar in both groups. Reduction in haematological toxicity consequent on chemotherapy was not observed in the C. parvum-treated patients. No additional benefit was observed when C. parvum was followed by DTIC and Actinomycin D chemotherapy compared with the results from the chemotherapy given alone, although C. parvum on this schedule had minimal toxicity.
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PMID:Corynebacterium parvum followed by chemotherapy (actinomycin D and DTIC) compared with chemotherapy alone for metastatic malignant melanoma. 377 45


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