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)

Adoptive immunotherapy of human cancer was investigated in our institution as part of a National Cancer Institute extramural group study. This treatment, for patients with metastatic malignant melanoma, hypernephroma, and colon carcinoma, consisted of three phases: (a) 5 days of i.v. high-dose (10(5) units/kg every 8 h) interleukin 2, (b) 6 1/2 days of rest plus leukapheresis; and (c) 4 days of high-dose interleukin 2 plus three infusions of autologous lymphokine-activated killer cells. Toxicities included fever, chills, tachycardia, hypotension, vomiting, diarrhea, and fluid retention. Ascorbic acid is known to be important to cell-mediated immunity, and it has been reported to be depleted during physiologically stressful events. Therefore, we determined plasma ascorbic acid levels in patients (n = 11) before adoptive immunotherapy and before and after Phases 1, 2, and 3 of treatment. Patients entering the trial were not malnourished. Mean plasma ascorbic acid levels were normal (0.64 +/- 0.25 mg/dl) before therapy. Mean levels dropped by 80% after the first phase of treatment with high-dose interleukin 2 alone (0.13 +/- 0.08 mg/dl). Mean plasma ascorbic acid levels remained severely depleted (0.08 to 0.13 mg/dl) throughout the remainder of the treatment, becoming undetectable (less than 0.05 mg/dl) in eight of 11 patients during this time. Values obtained from 24-h urine collections on two of two patients indicated that ascorbate was not excreted in the urine. Plasma ascorbic acid normalized in three of three patients tested 1 mo after the completion of treatment. Unlike the results for ascorbic acid, blood pantothenate and plasma vitamin E remained within normal limits in all 11 patients throughout the phases of therapy. Responders (n = 3) differed from nonresponders (n = 8) in that plasma ascorbate levels in the former recovered to at least 0.1 mg/dl (frank clinical scurvy) during Phases 2 and 3, whereas levels in the latter fell below this level.
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PMID:Severe hypovitaminosis C occurring as the result of adoptive immunotherapy with high-dose interleukin 2 and lymphokine-activated killer cells. 349 58

In vitro synergism between interferons (IFNs) and chemotherapeutic drugs has been demonstrated, and an enhancement of IFN's antiproliferative effects when combined with cimetidine has been suggested in melanoma patients. In this pilot study, 12 patients with advanced malignant melanoma received HuIFN beta by 30 min i.v. infusion at 30 X 10(6) u/m2 day for 4 days, followed by i.v. decarbazine (DTIC) 1.0 g/m2 on day 5, repeated every 4 weeks. Oral cimetidine, 300 mg q.i.d., was given continuously. All the patients had visceral (bulky) metastases. No objective responses were observed; however, two patients had stable diseases for 16 and 20 weeks, respectively. Mild chills and fever with IFN, and mild to moderate emesis with DTIC, were noted. No additive haemopoietic or hepatic toxicity was observed. Combination of HuIFN beta, DTIC, and cimetidine is relatively nontoxic, but does not appear to have a significant antitumor activity in patients with advanced malignant melanoma.
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PMID:Combination of fibroblast interferon (HuIFN beta), carboxamide (DTIC), and cimetidine for advanced malignant melanoma. 377 95

Fifteen patients with advanced malignancy were treated with escalating doses of recombinant beta ser 17 interferon (IFN). Doses ranging from 0.006 to 500 X 10(6) units/m2 were administered according to a dosage escalation scheme by iv push twice weekly (starting 1 week after an initial dose) for a planned minimum of 5 weeks, to be continued as a function of response. Toxic effects were broad in scope but generally low in grade. They included fever, malaise, leukopenia, proteinuria, nausea/vomiting, diarrhea, and mild elevations of serum transaminases and creatinine. In one patient, transient hypotension with bradycardia ensued. Malaise and fever increased somewhat with increasing dose. Doses of up to 500 X 10(6) units/m2 were tolerated without severe toxicity. A maximum tolerated dose was not defined. IFN pharmacokinetics followed a biphasic decay curve, with a distribution phase alpha-half-life of 9 minutes and an elimination phase beta-half-life of 103 minutes. Anti-IFN antibodies by the ELISA technique were present in seven of 15 patients. Presence of antibody did not correlate with toxicity or response. 2',5'-Adenylate synthetase levels were increased 2 and 24 hours after the initial dose, with a trend toward higher increments with higher doses. Minimal anti-tumor responses were seen in two patients with melanoma.
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PMID:Phase I study of recombinant beta ser 17 interferon in the treatment of cancer. 379 Dec 49

Echinomycin is a quinoxaline antibiotic that was originally isolated from Streptomyces echinatus. Based on its antitumor activity against two i.p. implanted murine tumors, the B16 melanoma, and the P388 leukemia, it was brought into clinical trials by the National Cancer Institute. Recent studies on its cytotoxic action have related its antitumor activity with its ability to bifunctionally intercalate with double stranded DNA. Toxicologic studies were carried out in CDF1 mice and beagle dogs using intravenous injections. For the mice studies the dose ranges were 288-692 mcg/kg (864-2076 mcg/m2) by single bolus, and 112-254 mcg/kg/day (336-762 mcg/m2/day) for five consecutive days. In the dog, dose ranges studied were 8.9-89.4 mcg/kg (178-1788 mcg/m2) by single bolus, and 3.4-33.5 mcg/kg/day (68-670 mcg/m2/day) for five consecutive days. The major toxic effects were found in the gastrointestinal, hepatic, and lymphoreticular systems. These were reversible at all but the highest dose, in dogs that had been treated for five consecutive days. Phase I clinical trials using various intravenous schedules were sponsored by the National Cancer Institute. Nausea, vomiting, reversible liver enzyme abnormalities, and allergic reactions were the most common toxicities encountered. Based on results from these studies, the National Cancer Institute has recently begun phase II trials in a broad range of diseases. These trials will further characterize echinomycin's toxic effects and its antitumor activity.
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PMID:Echinomycin: the first bifunctional intercalating agent in clinical trials. 391 Jun 10

4-Demethoxydaunorubicin (4-DMDR) was administered orally at the dose of 15 mg/m2 daily for 3 consecutive days at three-weekly intervals to 28 patients with advanced pretreated breast cancer and 9 patients with disseminated pretreated melanoma. A partial remission was observed in 6 out of 20 evaluable breast cancer patients (30%) for a median duration of 6 months and in one out of 7 evaluable patients with melanoma (14%) for a duration of 3 months. Side-effects included leucopenia in 78% of patients (less than 1000 wbc/cmm in 8%), nausea in 32% and mild vomiting in 16%. The preliminary results of this ongoing study on 4-DMDR administered orally show that the regimen is well tolerated in the majority of patients and that it has antitumour activity in advanced breast cancer.
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PMID:The new anthracycline 4-demethoxydaunorubicin by oral route in advanced pretreated breast cancer and melanoma. A pilot study. 391 81

Animal studies have indicated a "vomiting center" situated in the dorsal portion of the lateral reticular formation of the medulla at the level of the dorsal nucleus of the vagus. There is also a chemoreceptor trigger zone in the floor of the fourth ventricle in the area postrema which influences the vomiting center. A 63 year old man with a three year history of metastatic malignant melanoma presented with nausea, projectile vomiting, gait ataxia and diplopia associated with horizontal and vertical nystagmus. CT scan showed a solitary brainstem metastasis without hydrocephalus and he was treated with radiotherapy with resolution of his vomiting after four weeks. At post mortem three months later a metastasis was found in the right middle cerebellar peduncle and lateral tegmentum of the pons; there was no pathological change in the area of the vomiting center or area postrema. It is postulated that this lesion caused projectile vomiting because of involvement of either afferent projections to the vomiting center. The neuroanatomy of vomiting is discussed.
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PMID:The neuroanatomy of vomiting in man: association of projectile vomiting with a solitary metastasis in the lateral tegmentum of the pons and the middle cerebellar peduncle. 407 83

Etoposide (VP 16) is a semi-synthetic derivative of 4'- demethylepipodophyllotoxin , a naturally occurring compound synthesized by the North American May apple (Podophyllum peltatum ) and the Indian species Podophyllum emodi Wallich . Although podophyllotoxins are classical spindle poisons causing inhibition of mitosis by blocking mitrotubular assembly, etoposide inhibits cell cycle progression at a premitotic phase (late S and G2), probably via inhibition of DNA synthesis. There appears to be a selective antileukemic dose response relationship when compared to normal hematopoietic elements. Etoposide is effective when administered orally at about twice the recommended parenteral dosage. Schedule dependency in both animal models and clinical trials has been observed; multiple dosing over three to five consecutive days is superior to weekly single dose administration. Etoposide's dose-limiting toxicity is myelosuppression (leukopenia), which is quite predictable; alopecia and Gl toxicity (nausea, vomiting, stomatitis) occur in about 20-30% of patients given recommended dosages. Etoposide appears to be one of the most active drugs for small cell lung cancer, testicular carcinoma (the Food and Drug Administration approved indication), ANLL and malignant lymphoma. Etoposide also has demonstrated activity in refractory pediatric neoplasms, hepatocellular, esophageal, gastric and prostatic carcinoma, ovarian cancer, chronic and acute leukemias and non-small cell lung cancer, although additional single and combination drug studies are needed to substantiate these data. Its contribution in front-line combination chemotherapeutic regimens for these cancers will be better defined in the forthcoming years. Etoposide appears to have minimal activity in breast cancer and, based on current data, it is inactive against malignant melanoma, colorectal adenocarcinoma and cancer of the head and neck, although the dosage and schedules used in many of the Phase II studies may have been suboptimal.
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PMID:Etoposide: a semisynthetic epipodophyllotoxin. Chemistry, pharmacology, pharmacokinetics, adverse effects and use as an antineoplastic agent. 632 63

Twenty-four patients were evaluated in a non-randomized study to assess the effectiveness of dibromodulcitol (DBD) in Stage IV melanoma. Patients received 100 mg/m2 of DBD orally for 35 days. The dose was escalated to 130 mg/m2 and then to 160 mg/m2 if no significant hematologic toxicity occurred. There were no objective responses, including six patients who had had no prior chemotherapy. Five patients (21%) remained stable. Median survival was 151 days. Survival favored females, nonvisceral involvement pretherapy, and patients with a disease-free interval (DFI) of greater than 1 year. None of these advantages was statistically significant. Toxicity was predominantly hematologic, but nausea, vomiting, shortness of breath, and diarrhea were also seen. Oral DBD, using this dose and schedule, does not appear efficacious in advanced disseminated melanoma.
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PMID:A phase II study of dibromodulcitol (DBD) in stage IV melanoma. 650 78

The toxicity of intravenously administered Corynebacterium parvum was observed in 14 patients with stage II melanoma and in 14 patients with advanced ovarian carcinoma. Those with melanoma were rendered disease-free by surgery prior to treatment. The ovarian cancer patients had failed chemotherapy with alkylating agents and were receiving C. parvum prior to chemotherapy as part of an immunochemotherapy trial. Both clinical and laboratory parameters were observed. The mean daily C. parvum dose for melanoma patients was 2.03 mg/m2 and for ovarian carcinoma patients 2.02 mg/m2. The most important clinical toxic effects noted were fever, chills, blood pressure changes, headache, nausea, vomiting and diaphoresis. Laboratory toxicity was mild, with small decreases in hemoglobin levels, white blood cell counts and uric acid and albumin concentrations occurring in some patients. Serum bilirubin and SGOT levels tended to rise. In addition to determining the frequency of clinical toxic effects by treatment course, consideration was also given to frequency per treatment day, correlation of the occurrence of different toxicities in the same patient, time of onset of each toxicity and, for vital signs, to intensity of change and duration. In this analysis no major differences in toxicity were observed when C. parvum was given to the two patient groups.
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PMID:Corynebacterium parvum toxicity in patients with limited and advanced malignancy. 653 97

4-demethoxydaunorubicin (4-dm DNR), a new analog of daunorubicin, was tested at an every 3-week dose schedule in 63 evaluable patients with various forms of disseminated malignancy. Utilizing the intravenous (i.v.) route of administration, the maximum tolerated dose (MTD) was 15-18 mg/m2; with the oral route the MTD was 60 mg/m2. Myelosuppression represented the dose-limiting factor, and leukopenia was more often observed than thrombocytopenia. However, leukopenia was more frequently detected following i.v. administration while vomiting represented the most frequent toxic sign after oral administration. Loss of hair was moderate with either route of administration and comparatively less frequent and pronounced than that observed after doxorubicin (DX) and its analog 4'-epi-doxorubicin (4'-epi-DX). Aside from transient aspecific electrocardiographic changes recorded in 30% of patients, no cardiac toxicity was documented. Tumor response was documented in seven patients with malignant lymphomas, breast cancer, melanoma and carcinoma of uterine cervix. Two out of the seven responders achieved prolonged complete remission and four were resistant to doxorubicin. 4-dm DNR appears to be an analog worth further clinical trials.
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PMID:Phase I study of 4-demethoxydaunorubicin. 659 May 30


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