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)

The toxicity and/or the stimulation of natural killer cell activity that resulted from exposure to alpha-interferon varied according to circadian dosing time, both in mice and in human beings. Ten patients with advanced renal cell carcinoma or melanoma were treated with recombinant alpha-interferon-2b using a continuous 21-day intravenous schedule at circadian modulated rate. Patients received 15-20 MU/m2/day in an ambulatory care program. The drug was delivered via an external programmable-in-time pump. Thirty-nine courses of therapy were given (2-12 courses per patient). Severe side effects included World Health Organization grade III somnolence (one patient, 1 course) and grade III-IV neutropenia (five patients, 10 courses). Karnofsky performance status decreased by 40% in 3 patients (five courses). Two of these patients were withdrawn from the study because of toxicity. Disease was stabilized in four of the seven patients evaluable for response. Seven of the 10 patients are alive at 15 months' median follow-up. Two have continued with chronotherapy for 9+ and 13+ months, respectively. A large interpatient variability characterized the maximally tolerated dose. Two patients led their usual activities while receiving 20 MU/m2/day for three courses or more. Conversely, two patients exhibited severe side effects with 10 MU/m2/day. As compared with schedules of standard administration or continuous flat infusion, this circadian schedule of infusion allowed a large increment in total daily dose and dose intensity. A starting dose of 15 MU/m2/day was well tolerated by 8 of 10 patients and can be recommended using this circadian modulated schedule.
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PMID:A phase I trial of 21-day continuous venous infusion of alpha-interferon at circadian rhythm modulated rate in cancer patients. 176 78

Twenty-two patients with metastatic malignant melanoma received either 36 X 10(6) U (15 patients) or 18 X 10(6) U (7 patients) of human recombinant interferon alpha-2-A daily for 3 months by the intramuscular route, with progressive increase of dosage. This was followed in responders by a maintenance treatment consisting of 3 intramuscular injections per week in the same doses as those received at the end of the induction treatment. Out of 18 patients assessable for effectiveness, 1 had complete remission (7 months +) and 3 had partial response (52,61 and 82 days respectively), an overall improvement rate of 22%. The main side-effects observed were: pseudoinfluenza syndrome (100%), fatigue (100%), somnolence (95%), anorexia (90%) and haematological disorders. Dosage reduction was necessary in 13 of the 15 patients receiving 36 MU. This study shows that human recombinant interferon alpha-2-A has antitumoral activity in metastatic malignant melanoma. Other studies, notably with therapeutic combinations, are needed to determine the optimal dosage regimen of the drug and to increase its effectiveness.
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PMID:[Human recombinant leukocyte interferon alpha-2-A in 22 cases of metastatic malignant melanoma]. 295 23

Acivicin, an L-glutamine antagonist, was administered to 37 evaluable patients with refractory advanced solid tumors in a phase I trial. A total of 67 evaluable 72-hr iv infusions were given at 3- to 4-week intervals. Doses ranged from 3.0 to 90 mg/m2/course. Reversible CNS toxicity was dose-limiting and included lethargy, somnolence, anxiety, hallucinations, and paranoid psychoses. Four of five patients experienced unacceptable CNS toxicity at 90 mg/m2. Three of eight patients experienced reversible diaphoresis and chills without fever at 75 mg/m2, and two had dizziness and ataxia. Hematopoietic toxicity, nausea, emesis, and diarrhea were mild and dose-related. One patient developed a blue-green discoloration of the infusion arm. Serial plasma and urine specimens from 13 patients were assayed for acivicin using a microbiologic method. Peak plasma levels at the end of the 72-hr infusions correlated with dose and ranged from 0.09 to 1.10 microgram/ml. When data from six patients were fitted to a two-compartment open model, alpha-half-life ranged from 1.1 to 63 mins, while beta-half-life ranged fro 338 to 629 mins. Renal clearance ranged from 6 to 24 mL/min, and nonrenal clearance accounted for 58%-83% of the total drug clearance. CNS toxicity correlated with plasma acivicin levels which exceeded 0.9 microgram/ml for greater than 16 hrs, but not with peak plasma levels or with the integrals of the concentration x time curves. Minor responses were seen in one patient with melanoma, in one with epidermoid pulmonary carcinoma, and in two with colon carcinoma. A starting dose of 60 mg/m2/course was recommended for phase II trials, with possible escalation to 75 mg/m2 in the second course if the drug was well-tolerated.
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PMID:Phase I trial and pharmacokinetics of acivicin administered by 72-hour infusion. 687 83

High-dose thymidine (dThd) was given to 12 patients with advanced hematological and solid tumors. The dose schedule used was 75 g/sq m/day, given i.v. continuously for 5 days or more. Myelosuppression, especially leukopenia, was the dose-limiting toxicity. Nonhematological toxicities affected the gastrointestinal tract (nausea, vomiting, anorexia, diarrhea, and indigestion) and the central nervous system (somnolence, headache, visual illusions, and memory impairment). Patients who had received cumulative doses of dThd developed alopecia. Thymine crystals were noted in the urine after refrigeration. Tumor regression (less than partial remission) occurred in one patient with melanoma. Three of four patients with acute leukemia had a fall in peripheral white blood cell counts and blasts but no marrow improvement. Four patients with adenocarcinoma (three colon, one unknown primary) had stable disease. Pharmacokinetic studies revealed that, at a dThd dose of 75 g/sq m/day, millimolar concentrations of dThd and thymine can be achieved in the plasma. The half-life of dThd was approximately 100 min. One-third of the plasma concentrations was measurable in the cerebrospinal fluid. dThd was mainly excreted by the kidneys.
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PMID:Clinical phase I-II and pharmacokinetic study of high-dose thymidine given by continuous intravenous infusion. 747 Oct 98

The case history is reported of a patient with melanoma and advanced metastases, who died from massive cerebral bleeding. The lethal event was not caused by intracerebral metastasis but by thrombocytopenia. Depression of the bone marrow resulted from tumour infiltration of the skeleton, chemotherapy and vertebral irradiation. An increase of intracranial pressure triggered the cerebral bleeding, caused by haematemesis from a gastric metastasis directly preceding sudden somnolence.
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PMID:Massive lethal cerebral bleeding in a patient with melanoma without intracranial metastasis. 976 84

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is characterized by hyponatraemia due to water retention resulting from the persistent release of antidiuretic hormone (vasopressin). It may occur in a variety of malignant and non-malignant conditions, in particular in association with oat cell carcinoma, pulmonary and cerebral diseases. We report the case of a male patient affected by melanoma of the right temporal region with brain metastasis who developed acute headache, drowsiness, nausea, vomiting and pathological reflexes. Clinical and laboratory investigations led us to the diagnosis of SIADH. Restriction of fluid intake obtained a good clinical improvement with normalization of laboratory alterations; after 2 months the patient experienced a new episode of SIADH which was promptly treated. As melanoma has been occasionally observed in association with SIADH it should be included in the list of tumours that can cause this particular syndrome.
Melanoma Res 1998 Aug
PMID:Syndrome of inappropriate secretion of antidiuretic hormone in a patient affected by metastatic melanoma. 976 13

Thirty-one patients with advanced renal carcinoma or malignant melanoma were treated in the first feasibility study of alpha-interferon (Roferon) and the new oral immunomodulating agent, Linomide. Linomide 5 mg or 10 mg p.o. daily was given for 2 weeks; alpha-interferon was then added at 3 MU s.c. three times weekly, escalating in each patient by 3 MU per week, if tolerable, up to 12 MJ. The combination was poorly tolerated with nausea, vomiting, somnolence and myalgia commonly reported. Adverse events accounted for treatment withdrawal in ten patients and contributed to withdrawal in four other patients. Treatment with Linomide alone in the first 2 weeks led to a significant increase in white blood cells, neutrophils and platelets. When alpha-interferon was added, the platelet count decreased significantly over the following 6 weeks. Nineteen patients had white cell phenotype and function measured. After 2 weeks of 5 mg Linomide, a transient but significant decrease in the absolute number of activated T-helper cells (CD4+DR+) was observed. No changes in natural killer (NK) cell number or activity were observed. Twenty-two patients were evaluable for response. One with metastatic renal cell carcinoma had a complete response and six had stable disease. This study does not support the use of the combination because significant toxicity was seen without the anticipated immunological benefits.
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PMID:A feasibility study of roquinimex (Linomide) and alpha interferon in patients with advanced malignant melanoma or renal carcinoma. 986 73

Interferon-alpha (IFN-alpha) is of high interest in the adjuvant treatment of malignant melanoma. During long term treatment, psychiatric side effects play an important role and not infrequently lead to reduction or discontinuation of therapy. Most common are sleeping disturbance, agitation, weariness, sleepiness, irritability, social withdrawal and depression, which most often develop during the first three months of the therapy. Also more severe side effects may occur, like delirium, organic depression, psychotic episodes and organic personality change, which in some patients may even lead to suicidal thoughts or suicide attempts, which is illustrated in two case reports. Therapeutic intervention depend to the severity of side effects. Moderate depressive syndromes may successfully be treated by antidepressive drugs like serotonin reuptake inhibitors (SSRI), which may even allow continuation of IFN-alpha therapy. In patients with severe depression or organic personality changes with increased risk of suicide, immideate discontinuation of IFN-alpha therapy is mandatory and treatment in a psychiatric hospital must be considered.
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PMID:[Psychiatric side effects during adjuvant therapy with interferon-alphain patients with malignant melanoma. Clinical evaluation as well as diagnostic and therapeutic possibilities]. 1050 82

Based on evidence that granulocyte-macrophage colony stimulating factor (GM-CSF) induces a potent systemic antitumor immunity, we tested recombinant GM-CSF in advanced melanoma. Seven patients with histologically confirmed cutaneous melanoma metastases were treated with perilesional intracutaneous injections of recombinant GM-CSF and observed for a follow-up time of 5 y. All but two patients had a decrease in the total number of metastases. At the end of the 5 y follow-up three of the seven patients are still alive with only one patient receiving other than surgical therapy, and one patient died tumor free at the age of 93. The remaining three patients died from progressive melanoma. Perilesional intradermal GM-CSF therapy resulted in a mean survival time of 33 mo. The treatment was well tolerated and no side-effects other than local erythema at the injection sites and mild drowsiness were seen. Immunohistochemical analysis with staining for CD14 and GM-CSF receptor demonstrated an increased infiltration of monocytes into both injected and noninjected cutaneous melanoma metastases compared with lesions excised prior to the initiation of therapy. The same was true for CD4- and CD8-positive lymphocytes. This phenomenon, together with GM-CSF-induced leukocyte counts of more than 20,000 during therapy, support the possible impact of a systemic over a locally induced reaction by GM-CSF. To our knowledge this is the first report that intracutaneously injected GM-CSF results in long-lasting reduction of melanoma metastases.
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PMID:Perilesional injection of r-GM-CSF in patients with cutaneous melanoma metastases. 1151 18

Sleep difficulty is a prominent concern of cancer patients, yet there has been no large study of the prevalence and nature of sleep disturbance in cancer patients. This cross-sectional survey study examined: (a) the prevalence of reported sleep problems in patients attending six clinics at a regional cancer centre; (b) sleep problem prevalence in relation to cancer treatment; and (c) the nature of reported insomnia (type, duration, and associated factors). For three months, all patients attending clinics for breast, gastrointestinal, genitourinary, gynecologic, lung, and non-melanoma skin cancers were offered a brief sleep questionnaire. Response rate was 87%; the final sample size was 982. Mean age of respondents was 64.9 years (SD 12.5). The most prevalent problems were excessive fatigue (44% of patients), leg restlessness (41%). insomnia (31%), and excessive sleepiness (28%). Chi square tests showed significant variation among clinics in the prevalence of most sleep problems. The lung clinic had the highest or second-highest prevalence of problems. The breast clinic had a high prevalence of insomnia and fatigue. Recent cancer treatment was associated with excessive fatigue and hypersomnolence. Insomnia commonly involved multiple awakenings (76% of cases) and duration > or = 6 months (75% of cases). In 48% of cases, insomnia onset was reported to occur around the time of cancer diagnosis (falling within the period 6 months pre-diagnosis to 18 months post-diagnosis). The most frequently identified contributors to insomnia were thoughts, concerns, and pain/discomfort. In a multivariate logistic regression analysis, variables associated with increased odds of insomnia were fatigue, age (inverse relationship), leg restlessness, sedative/hypnotic use, low or variable mood, dreams, concerns, and recent cancer surgery. This study provides new information about sleep-related phenomena in cancer patients, information which will be useful in planning supportive care services for cancer patients.
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PMID:Sleep disturbance in cancer patients. 1205 48


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