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)

Increasing doses of saponin fraction QS-21 were administered as immunological adjuvant in a Phase 1 trial with a constant dose of the melanoma ganglioside GM2 covalently attached to keyhole limpet haemocyanin (KLH). Twenty-eight patients with AJCC Stage III or IV melanoma who were free from disease after surgery were treated with six vaccinations administered subcutaneously over a 5-month period. Local and systemic reactions were QS-21 dose-related. Doses of < or = 100 micrograms induced mild local tenderness and inflammation at vaccination sites lasting 2-4 days and occasional brief low-grade fever and malaise, but no significant incapacitation. The 200 micrograms dose induced low-grade fever and malaise after 30% of vaccinations and local reactions as large as 20 cm in diameter were seen in all patients, resulting in discomfort with usage of the injected extremity for 5-10 days. The titres of IgM and IgG antibodies against GM2, and IgG antibodies against KLH, were highest at the 100 and 200 micrograms QS-21 doses. No antibodies against QS-21 were detected. This trial identifies the 100 micrograms dose of QS-21 as the optimal well tolerated dose for induction of antibodies against both the melanoma ganglioside/GM2 and the protein KLH in melanoma patients.
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PMID:Phase 1 trial of immunological adjuvant QS-21 with a GM2 ganglioside-keyhole limpet haemocyanin conjugate vaccine in patients with malignant melanoma. 785 91

Interleukin (IL-4) is a pluripotent cytokine that stimulates proliferation of activated T-cells and has antineoplastic activity against human renal tumors in animal systems. In phase I trials, IL-4 could be tolerated at doses up to 20 micrograms/kg, with dose-limiting toxicities consisting of fever, fluid retention, nasal congestion, and mucositis. We report the results of two separate Phase II trials of IL-4 in 30 patients with metastatic malignant melanoma and 19 patients with advanced renal cancer. IL-4 was administered intravenously every 8 h for 14 doses in two 5-day courses separated by a 9-day interval. The first 27 patients were treated at a dose of 800 micrograms/m2, but after three of these patients developed cardiac toxicities, the dose was decreased to 600 micrograms/m2. One complete response occurred in a patient with metastatic melanoma (duration > or = 30 months). No responses were seen among the patients with renal cancer. The most frequent side effects were fever, nausea, malaise, nasal congestion, and diarrhea. Reversible hepatic and renal dysfunction were also common. Hypotension was infrequent, but transient weight gain due to fluid retention was common. The major life-threatening toxicities were cardiac and gastrointestinal. Suspected cardiac ischemia was observed in two patients, pericarditis in one, and arrhythmias in two. Three patients had major upper gastrointestinal bleeding without evidence of local tumor. We conclude that IL-4, when given as a single agent on this schedule at maximum tolerated dose, does not possess meaningful activity in renal cancer or melanoma.
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PMID:Phase II studies of recombinant human interleukin-4 in advanced renal cancer and malignant melanoma. 813 48

Patients with advanced renal cell carcinoma, previously failed maximal treatment with standard chemo-hormonal-radiation therapies, were treated with plant lectin phytohemagglutinin (PHA)-stimulated autologous peripheral blood lymphocytes in a 10-year study with a 16-year follow up period. In a phase I-II setting, 52 patients were given subcutaneously 40-80 x 10(6) PHA-stimulated lymphocytes weekly for 3 weeks and then escalated to a maximum number of 80 x 10(9) lymphocytes over the next 9 weeks at 3 week intervals. In vitro blastogenesis under study conditions (10 micrograms/ml PHA for 72 hr) measured by [3H]thymidine uptake was optimal with lymphocyte stimulating indexes approaching 300. Lymphocytes obtained from patients with breast cancer, melanoma and renal cell carcinoma responded to PHA similarly to those from normal volunteers. All patients that responded developed erythematous reactions at the sites of injection; malaise, joint paint and chill-fever for 24-48 hr. The patients that responded the best were those with at least 1 positive reaction out of 4 skin tests (tuberculosis, yeast, dermatophytin, mumps) prior to therapy. All toxicity was transient and did not exceed Grade I based on criteria of the Southwest Oncology Group. The majority of patients developed a lymphopenia in the first 24 hr followed by a lymphocytosis 48-72 hr later. For some patients the lymphocytosis was as much as 30% atypical lymphocytes. Of 41 evaluable patients, there were 5 complete responses, 8 partial responses, 3 stable diseases, and 25 progressive disease. The overall response rate was 32% and the median survival was 2.8 years.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adoptive immunotherapy of advanced renal cell cancer using PHA-stimulated autologous lymphocytes. 826 79

Merbarone, NSC 336628, is an investigational anticancer drug with activity against experimental animal tumors including melanoma. This paper presents results of a Phase II clinical study of merbarone in patients with biopsy proven stage IV malignant melanoma without prior chemotherapy and with no evidence of CNS involvement. Thirty-five patients with median age 58 (range 27-81), with performance status 0-2 were treated with merbarone 1000 mg/m2/day for five days by intravenous continuous infusion repeated every 3 weeks. All patients (21 males and 14 females) were evaluable for toxicity. Two patients were not evaluable for response having been removed from protocol treatment due to toxicity and received other treatment during the first course of chemotherapy. Among the evaluable patients there was one complete response in a supraclavicular lymph node lasting four months and one partial liver response lasting three months. The remaining thirty-one patients were non-responders. Of these one had a stable disease lasting 21 months. The overall objective response rate was 6% (2/35) with a 95% confidence interval of 1%-19%. Twenty-six of the 35 patients have died. The estimated median survival of the entire group was 9 months with a 95% confidence interval six to eleven months. Renal toxicity was dose-limiting and manifested as increasing serum creatinine (54% of patients), proteinuria (51%) and hematuria (9%). One patient experienced grade 4 creatinine increase, proteinuria and acute renal failure. Other toxicities included nausea (71%), vomiting (51%0, malaise (23%), weakness (20%), alopecia (17%), diarrhea (17), anorexia (14%) transaminase (SGOT, SGPT) increase (14%), constipation (14%), alkaline phosphatase or 5'nucleotidase increase (9%), and fever (9%). Hematologic toxicity (granulocytopenia, leukopenia, and anemia) was generally mild and infrequent (29%, only one patient had grade 4 granulocytopenia). Overall 9 patients (26%) had at least one grade 3 toxicity. We conclude that merbarone at this dose and schedule has detectable but minimal activity in the treatment of metastatic malignant melanoma and given the significant renal toxicity this schedule does not merit further evaluation in this disease.
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PMID:Evaluation of merbarone (NSC 336628) in disseminated malignant melanoma. A Southwest Oncology Group study. 861 77

In 1939 F. Wegener published a report concerning a peculiar febrile syndrome with necrotizing inflammation of the upper respiratory tract, focal glomerulonephritis and systemic angiitis (Wegener 1939). Clinically Wegener's granulomatosis can be divided into a limited and a generalized form. We describe a patient presenting with unilateral ocular symptoms suspicious of a neoplasm, one episode of angina pectoris and general malaise without any clinical signs of upper respiratory tract involvement. Before Wegener's granulomatosis was diagnosed by a positive titre of antineutrophil cytoplasmic antibodies and open lung biopsy, immunoscintigraphy for malignant melanoma showed a false positive result. Systemic treatment with corticosteroids and cyclophosphamide resulted in an improvement of the ocular symptoms within weeks.
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PMID:Subretinal tumour in a patient with a limited form of Wegener's granulomatosis. 875 Nov 30

High response rates in patients with metastatic melanoma have been achieved with combination chemoimmunotherapy. A response rate of 62% in 45 patients has been reported for treatment with dacarbazine, bleomycin, vincristine, lomustine (BOLD) plus interferon alpha (IFN-alpha). We conducted a multicentre phase II study to confirm these results. Melanoma patients with distant metastases were treated as outpatients with dacarbazine 200 mg m(-2) on days 1-5, vincristine 1 mg m(-2) on days 1 and 4, bleomycin 15 mg on days 2 and 5 i.v. and lomustine 80 mg orally on day 1, repeated every 4 weeks. IFN-alpha-2b was initiated s.c. on day 8 at 3 MU daily for 6 weeks, and 6 MU t.i.w. thereafter. Forty-three patients entered the study. The median number of metastatic sites was three (range 1-5), and 81% of patients had visceral metastases. Nine patients had brain metastases, and seven patients were systemically pretreated. Among the 41 patients that were evaluable for response, the response rate was 27% (95% CI 14-3%), with one complete and ten partial remissions. The response rate in 25 previously untreated patients without brain metastases was 40% (95% CI 21-61%). Median duration of response was 6 (range 2-14+) months; median overall survival was 5 (1-26) months. The main toxicity was malaise/fatigue. We confirm that BOLD plus IFN-alpha has activity in metastatic melanoma. The lower response rate in our study compared with the previous report is probably related to patient selection, as in the previous study 46% of patients had stage III disease, whereas all our patients had stage IV disease, which is associated with a worse prognosis.
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PMID:Chemoimmunotherapy with bleomycin, vincristine, lomustine, dacarbazine (BOLD) plus interferon alpha for metastatic melanoma: a multicentre phase II study. 923 31

Malignant melanoma is increasing in incidence in this country. Metastatic disease generally responds poorly to most chemotherapy drugs. Immunologic and biologic agents have shown some activity in this disease. Interleukin 4 (IL-4) is a cytokine produced by activated T-lymphocytes with pluripotent activities including growth inhibition of various tumor cell lines in vitro and immune- mediated tumor growth inhibition in in vivo animal tumor models. In this phase II trial, patients with advanced malignant melanoma with no prior systemic therapy for metastatic disease and Southwest Oncology Group performance status 0-1 were treated with recombinant human IL-4 at a dose of 5 micrograms/kg/day by daily subcutaneous injection days 1-28 followed by a 7-day rest period, after which the cycle was repeated. Thirty-six patients were registered to this study. Two patients were ineligible by study criteria. Among the 34 eligible patients, there was 1 complete response, 0 partial responses, 2 stable/no responses, 27 increasing disease/progression, 1 early death, and 3 patients whose assessment was inadequate to determine response. The overall estimated response rate was 3% (1 of 34) with a 95% confidence interval 0.1-15%. The duration of the complete response is 421+ days. Thirty-one of the 34 eligible patients have died. The estimated median survival is 6 months (95% confidence interval 4-9 months). The most common toxicities were elevated liver function tests, nausea/vomiting/diarrhea, malaise/fatigue, edema, headache, myalgias/arthralgias, and fever/chills. Despite promising preclinical growth inhibitory and immunomodulatory effects, IL-4 in this dose and schedule showed only low antitumor activity. Alternative methods and routes of administration or combinations of IL-4 with other cytokines might produce greater antitumor effects.
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PMID:Phase II trial of recombinant human interleukin-4 in patients with disseminated malignant melanoma: a Southwest Oncology Group study. 980 39

Malignant melanoma is increasing in frequency at a rapid rate in the United States. Metastatic disease is chemoresistant with DTIC considered the most active single agent. CI-980 is a synthetic mitotic inhibitor that blocks the assembly of tubulin and microtubules. It has shown cytotoxic activity against a broad spectrum of murine and human tumor cell tines. CI-980 can cross the blood brain barrier, is effective when given orally or parenterally, and is active against multidrug resistant cell lines overexpressing P-glycoprotein. In this trial, patients with disseminated melanoma with measurable disease, SWOG performance status of 0-1, no prior chemotherapy or immunotherapy for metastatic disease, and adequate hepatic and renal function, were enrolled. Treatment with CI-980 was given by 72 h continuous i.v. infusion at a dose of 4.5 mg/m2/day, days 1-3 every 21 days. Twenty-four patients were registered on this study with no patients ineligible. They ranged in age from 33-78 with performance status of 0 in 15 patients and 1 in 9 patients. Nineteen patients had visceral disease with 12 having liver involvement. There were no confirmed responses. The overall response rate was 0% (95% CI 0%-14%). The median overall survival is eleven months (95% CI 4-14 months). The most common toxicities were hematologic and consisted of leukopenia/granulocytopenia and anemia, with nausea/vomiting and malaise/fatigue/weakness also frequent. CI-980 administered at this dose and schedule has insufficient activity in the treatment of disseminated malignant melanoma to warrant further investigation.
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PMID:Phase II trial of CI-980 in patients with disseminated malignant melanoma and no prior chemotherapy. A Southwest Oncology Group study. 1156 81

Treatment of malignant melanoma of the external ear presents unique challenges. Because of the significant debate regarding the efficacy and validity of using sentinel lymph node mapping for the treatment of ear melanomas, data for a population of patients with melanomas of the ear who underwent surgical excision and reconstruction were reviewed to determine the efficacy of sentinel node mapping. A retrospective chart review of cases treated by a single surgical oncologist was performed. All patients who were treated for malignant melanomas and required reconstruction of the external ear by the plastic surgical service between 1995 and 2001 were identified. Nineteen patients were selected, of whom nine underwent sentinel node mapping. The average age of the patients was 65.2 years. Evaluation of melanoma depth, medical history, surgical margins, lymph node metastasis, and recurrence was performed. Lymphoscintigraphy with technetium-99-sulfur colloid and 1% Lymphazurin (isosulfan blue; Zenith Parenterals, Rosemont, Ill.) demonstrated widely variable lymphatic drainage patterns. The lower tail of the parotid gland and the upper cervical area were the two most common locations. The average number of sentinel nodes identified and removed was 3.7. The average Breslow thickness for these patients was 2.3 mm. None of these patients demonstrated micrometastatic disease in their sentinel nodes. The most common reconstructive procedure after surgical resection was the use of rotational advancement flaps. Localization of radioactivity, as detected with external technetium-99 scanning, was the most reliable method for detection of the sentinel lymph node basins and the individual nodes. The average value for the primary injection site was 8375 counts per second, and the average value for the nodes removed was 973.5 counts per second. Of the nine patients who underwent sentinel lymph node mapping, only one, with an initial lesion depth of 5 mm, developed a local recurrence. The average follow-up period in this study was 21 months (range, 12 to 79 months). All patients in this study were evaluated at least 1 year after the initial surgical resection. Patients were monitored by the same surgical oncologist every 3 months for the first 2 years. Little can be found in the literature regarding the efficacy of sentinel node biopsies for ear melanomas. Larger studies are indicated; however, it seems that this method is practical for designing therapeutic methods for patients with melanoma of the ear.
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PMID:Evaluation of nodal patterns for melanoma of the ear. 1506 Mar 90

Metastatic heart tumours are rare. Most arise from lung, breast and renal cancerous primaries, soft-tissue sarcoma and malignant melanoma. We report the case of a 32-year-old policeman who presented to the emergency department very short of breath with a five-week history of weight loss and malaise. He was noted to have a mass in his right testicle, numerous 2-3 cm round shadows on chest X-ray (CXR) and a large mass within the right ventricular cavity. After much informed debate, the patient was treated solely with chemotherapy with the expectation of cure. We set out this argument and recommendations for future patients with this unusual problem.
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PMID:Intra-cardiac metastasis from testicular non-seminoma germ cell tumour; to resect or not to resect. 2085 55


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