Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A clinical phase II study of recombinant human leukocyte interferon A (rIFN-alpha A, Ro 22-8181) for various skin malignant tumors was jointly conducted at nine medical institutes across the country in order to study its clinical effect and side effects. Patients received Ro 22-8181 alone in doses ranging from 3 X 10(6) U/day to 50 X 10(6) U/day either by intramuscular injection or by local injection. Good response was obtained in one (4.8%) of 21 patients treated by intramuscular injection and in 26 (72.2%) of 36 patients treated by local injection. The percentage of good responses achieved by local injection for individual diseases was 55.6% (5/9) for metastatic malignant skin melanoma, 100% (11/11) for cutaneous malignant lymphoma, 100% (5/5) for extramammary Paget's disease, 75% (3/4) for intraepidermal cancer and 50% (2/4) for metastatic skin cancer. Main side effects were fever, anorexia, general fatigue, chills, nausea and vomiting. Abnormal laboratory data included leukopenia, and elevation of GOT and GPT, although their incidence was lower with local injection than with intramuscular injection. Side effects were mostly improved by reduction of the dose or discontinuation of the treatment.
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PMID:[Phase II study of recombinant leukocyte A interferon (Ro 22-8181) in skin malignant tumors]. 298 7

A phase I-II study of human recombinant interferon gamma (rIFN-gamma) was conducted in patients with various advanced cancer refractory to standard chemotherapies. In the phase I study, seven patients received 14 courses of escalating doses ranging from 2 X 10(6)U/m2 to 64 X 10(6)U/m2 by 1-hour intravenous infusion for 5 consecutive days. The toxicities were high fever with chills, anorexia, occasional nausea and vomiting, elevation of serum GOT, and dose-related leukopenia and neurotoxic symptoms such as heavy fatigue with somnolence or lethargy, both of which were reversible. The pharmacokinetics showed that the peak levels of serum rIFN-gamma activity were dose-related but decreased rapidly to below measurable levels within 6 hours after infusion in patients receiving less than 12 X 10(6)U/m2. Considering these data, the dosage of rIFN-gamma 6 X 10(6) U/m2 by daily intramuscular injection for more than 4 weeks was selected for the early phase II study. There was no partial response out of 11 evaluable patients but a stable condition was observed in 2 cases of renal cell carcinoma and one case each of breast cancer and ovarian cancer. All toxicities seen were similar to those observed in the phase I study, but no tachyphylaxis developed with continued dosage. The antitumor effect of rIFN-gamma remains to be evaluated in a further study employing higher doses.
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PMID:[Phase I-II study of recombinant interferon gamma]. 298 59

Eighteen patients with solid tumours were treated with human recombinant interferon-gamma at escalating dose levels starting at 1 X 10(6) units/m2 per infusion and rising through 3 X 10(6), 6 X 10(6), 9 X 10(6) and 22 X 10(6) to a maximum of 110 X 10(6) units/m2 per infusion. The IV infusions were given three times a week over a 4-week period. Side effects were seen in all patients, but were mild except at the highest dose. Acute dose-related effects included pyrexia, tiredness, thirst, chills and rigors. Chronic dose-related effects included anorexia, lethargy, weakness, disorientation, a trace of proteinuria and minimal rises in liver enzymes. In addition, effects were observed which were not related to dose. These included headache, nausea and vomiting, backache, myalgia, flatulence and a mild, transient reduction in neutrophils and erythrocytes. At the highest dose level dose-limiting toxicity was observed, consisting in severe tiredness and anorexia, hypotension, disorientation and changes on the electrocardiograph. Overall, toxicity was similar to that seen with preparations of interferon-alpha, except that no tolerance to the effects of interferon-gamma was noted. We observed less hepatic and haematological toxicity, but also recorded flatulence, handcramps and electrocardiograph changes, which have not been reported with interferon-alpha. When given according to this regimen, doses of 22 X 10(6) units/m2 per infusion of recombinant interferon-gamma were generally well tolerated by the patients.
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PMID:A toxicity study of recombinant interferon-gamma given by intravenous infusion to patients with advanced cancer. 309 8

24 patients with advanced, histologically proven cancer were treated with difluoromethylornithine 2.25 g/m2 orally every 6 h for the first 7 days of each 4-week treatment cycle. These patients also received daily i.m. doses of recombinant human alpha 2a-interferon (IFN) on Days 3 through 7 of each cycle. IFN doses of 3, 6, 12, 24, 36, and 48 X 10(6) units/m2 have been studied utilizing three patients at each daily dose level. Three additional patients have been observed at each of the two highest doses for better toxicity definition. This combination produced slight transient declines in leukocyte and platelet counts and transient rises in serum aspartate aminotransferase; however, these changes were no more pronounced at the higher IFN doses than at daily doses of 6 X 10(6) units/m2. Mild nausea and vomiting occurred in most patients and mild diarrhea also was common at all IFN dose levels. Chills, fever, myalgia, lethargy and fatigue, and anorexia were also observed at all IFN doses; however, lethargy and fatigue (lassitude) seemed to be the major factor which limited patient tolerance of IFN to 48 X 10(6) units/m2 daily. No ototoxicity was identified clinically or audiometrically and no life-threatening toxicity has occurred. Initial Phase II studies in melanoma are currently in progress.
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PMID:Phase I study of difluoromethylornithine in combination with recombinant alpha 2a-interferon. 314 Oct 46

The combination of cisplatin 100 mg/m2 every 3 weeks and mitoguazone 500 mg/m2 every week with dose escalation was administered as a 9-week induction regimen to 27 patients with previously untreated Stage III or IV squamous cell carcinoma of the head and neck. This was followed by full-course radiation therapy for unresectable patients or surgery and postoperative radiation therapy for those with resectable disease. Sixteen patients had bulky unresectable disease, and ten were candidates for curative resection at study entry. Of 26 patients evaluable for response to chemotherapy, there were seven complete responses (CR) (five of six pathologically confirmed) and ten partial responses (PR) (65% CR + PR). Toxicity was generally mild with Grade 3 or 4 nausea and vomiting occurring in 15% and diarrhea in 12%. Nineteen percent of the patients developed transient nephrotoxicity (serum creatinine greater than 2), 62% anemia (hemoglobin decrease greater than 2 g/dl), 23% leukopenia (leukocyte count less than 3500 cells/microliters) and 8% thrombocytopenia (platelets less than 50,000 cells/microliters). Anorexia, fatigue, and weight loss occurred in nearly all patients. The median survival time of all patients was 17.5 months; complete responders, 43 months; partial responders, 16 months; and nonresponders, 9 months (P = 0.0025). In a multivariate analysis of stage, primary site, resectability status, response to chemotherapy, and local treatment (surgery plus radiation versus radiation), complete response was the only statistically significant covariate for survival. In Phase II single agent trials, mitoguazone has been shown to have a 15% response rate in head and neck cancer and cisplatin, a 30% to 40% response rate (less than 10% CR). Thus, our results, both complete and overall response rates, were higher than would be expected from either drug alone. A possible mechanism for this high response rate may be mitoguazone-induced cell synchronization. In vitro studies demonstrate the accumulation of tumor cells exposed to mitoguazone in S- and G2-phases of the cell cycle. These results would support further evaluation of mitoguazone in combination to explore the theoretical potentiation of antitumor effects by sequencing with cycle-specific agents.
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PMID:Cisplatin and mitoguazone. An induction chemotherapy regimen in advanced head and neck cancer. 317 46

Carbetimer, a new synthetic low molecular weight polyelectrolyte with a novel structure displayed antitumor activity in a number of animal tumor model systems and in vitro investigations. Based on these findings it was brought to a phase I clinical trial in patients with advanced malignant disease after failure of conventional treatment or with no conventional treatment available. Forty-eight patients received 98 courses. The schedule was a one hour i.v. infusion every four weeks. The starting dose was 180 mg/m2 and dose escalation was performed according to a modified Fibonacci formula up to 16,690 mg/m2. At least three patients were treated at each dose level and each patient was eligible to receive repeat courses at the same dose, until progressive disease or dose-limiting toxicity intervened. No hematological toxicity was encountered. Some adverse effects such as reversible proteinuria, hypercalcaemia, pain at infusion site, nausea and vomiting and fatigue were seen partly in a dose-related manner but did not represent the maximum tolerated dose (MTD). The limiting toxicity at the highest dose level of 16,690 mg/m2 consisted of ocular symptoms ('light flashes') accompanied by a modest decrease of blood pressure and nausea or vomiting during a one hour infusion. 16,690 mg/m2/1 hour was considered the MTD. There were four deaths on study, all considered disease-related. Fourteen patients had stable disease for more than two courses, which, however, could also be explained by the natural course of disease. No clear-cut antitumor responses were noted in our study center. The recommended dose for phase II trials derived from our results is 12,550 mg/m2/2 hours.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase I trial of the polyelectrolyte carbetimer administered i.v. once every four weeks. 319 84

In order to further extend the duration of remission induced by high-dose CAF therapy, maintenance therapies based on long-term oral administration of cyclophosphamide and fluorouracil (CF) were applied for patients with advanced and recurrent breast cancer. The duration of remission was compared by the envelope method among the basic therapy (Arm I), Arm I plus intermittent administration of adriamycin (Arm II) and Arm I plus tamoxifen from the start of high-dose CAF therapy (Arm III). The response rate of 163 evaluable patients in 30 institutes was 42.1% (27/57) and 44.4% (25/54) for Arm I and Arm II (CAF therapy). The rate for Arm III (CAF therapy) was 61.5% (32/52), a little higher than that for the other two. As side effects due to the induction therapy, alopecia, fatigue, anorexia, nausea and vomiting, and leukopenia were observed in a relatively high proportion of patients. Mean values of CR duration, PR duration and the whole duration of remission in responding patients were 14.0 approximately 21.5 weeks, 24.0 approximately 32.2 weeks and 28.0 approximately 42.6 weeks, respectively, without any significant difference among the three groups given different maintenance therapies. The mean values of survival duration in responding patients were 27.1, 22.0 and 17.2 months, respectively for Arm I, Arm II and Arm III no significant difference being recognized in this point, either.
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PMID:[Clinical evaluation of adriamycin in advanced and recurrent breast cancer (No. 4)--Joint study by 30 institutes on the duration of remission using various maintenance therapies in patients treated with CAF. Clinical Study Group of Adriamycin for Breast Cancer in Japan]. 338 38

A phase II study of epirubicin, a new anthracycline derivative, was performed in 23 patients with advanced gastric cancer. Epirubicin was administered intravenously at a dose of 20-30 mg/m2/day for two or three consecutive days every two or three weeks. Sixteen cases were evaluable and there were two partial responses and one minor response. Overall response rate (more than PR) was 12.5% (2/16). Leukopenia (less than 4,000/mm3) and anemia (less than 11.0 g/dl) were observed in 71.4% and 69.2% of patients, respectively. No thrombocytopenia was observed. Other toxicities were alopecia (71.4%), nausea and vomiting (42.9%), anorexia (25.0%), stomatitis (12.5%), fatigue (12.5%), fever (6.3%) and tachycardia (6.3%), but these effects were relatively mild in most cases.
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PMID:[Phase II study of epirubicin on gastric cancer--a cooperative study of the Tokai Cancer Chemotherapy Group]. 346 May 30

Twenty-nine patients with recurrent or advanced, incurable head and neck cancer were entered into a phase I-II trial of carboplatin in combination with 5-fluorouracil (5-FU), 1,000 mg/m2/d continuous intravenous (IV) infusion for five days every 28 days. The initial dose of carboplatin was 300 mg/m2 for patients with Karnofsky performance scores greater than or equal to 70%, and 240 mg/m2 for patients with scores of 50% to 60%. Subsequent doses were modified to achieve grade 2 myelo-suppression: WBC, 2,000 to 2,999 cells/microL; granulocytes, 1,000 to 1,499 cells/microL; and platelets, 50,000 to 75,000 cells/microL. Dose levels were 180, 240, 300, 360, and 420 mg/m2. Twenty-eight patients had squamous-cell cancers and one had an adenoid cystic carcinoma of the parotid. There were 26 patients with recurrent disease; 22 had received prior RT; only two had received other chemotherapy immediately before study entry. Three patients had newly diagnosed incurable stage IV disease. The median performance status was 80% (range, 60% to 90%). All patients had objectively measurable disease, and 28 were evaluable for response. There were three complete responses (CRs) and ten partial responses (PRs) (48% CR and PR); the median duration of response was 4.7 months (range, 1.5 to 15+ months). Dose-limiting toxicities were granulocytopenia, thrombocytopenia, and stomatitis. Prolonged myelosuppression delayed retreatment in eight patients and delayed 19 of 107 (18%) courses. Stomatitis occurred in 61% and diarrhea in 29%. 5-FU dosage was decreased in ten patients (36%) for grade 2 or greater stomatitis or diarrhea. Mild to moderate nausea and vomiting occurred in 66% of patient trials in which no pretreatment antiemetics were administered. Other toxicities included phlebitis from 5-FU in 71%, skin toxicity in 11%, mild alopecia in 25%, and fatigue in 54% of patients. Nephrotoxicity (creatinine greater than 2.0 mg/dL) occurred in one patient. The dose of carboplatin resulting in grade 2 toxicity was 180 mg/m2 in one patient, 240 mg/m2 in one, 300 mg/m2 in seven, 360 mg/m2 in ten, and 420 mg/m2 in one. Based on these results, we recommend a starting dose of carboplatin, 300 mg/m2, in combination with five days of continuous infusion 5-FU. In this dose and schedule, this combination was well tolerated and demonstrated antitumor activity in head and neck cancer. To confirm these promising results, a Southwest Oncology Group prospective randomized trial is in progress comparing carboplatin and 5-FU, cisplatin and 5-FU, and standard-dose weekly methotrexate in recurrent-disease patients.
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PMID:A phase I-II trial of carboplatin and 5-fluorouracil combination chemotherapy in advanced carcinoma of the head and neck. 354 42

Nine patients with hormone-resistant prostate carcinoma were treated with subcutaneous injection of recombinant human interferon-alpha 2 (rHuIFN-alpha 2), 5-10 X 10(6) U/m2, three times a week. One patient had a mixed clinical response with reduction of bone pain. The study was closed due to intolerable grade III and IV toxicities including weight loss (8/9), fatigue/malaise (7/9), central nervous system toxicity (4/9), leukopenia (3/9), and uncontrollable nausea and vomiting (2/9). These toxicities resulted in deterioration of performance status. It is concluded that rHuIFN-alpha 2, at least at the dose and schedule studied, should not be used for the treatment of patients with hormone-resistant prostate carcinoma.
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PMID:Toxicities of human recombinant interferon-alpha 2 in patients with advanced prostate carcinoma. 357 90


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