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)

Fifty-two patients with metastatic or recurrent non-small-cell lung cancer (NSCLC) were treated, during a phase II trial, with methylglyoxal-bis-(guanylhydrazone) (MGBG). Of the 44 patients who had adequate trials, 4 had partial responses (PR), for an overall 9% PR rate. Response durations ranged from 3 to 5+ months. Prior treatment with chemotherapy may have adversely affected response rate; 15% of previously untreated patients responded, compared to only 4% of previously treated patients. A syndrome of weakness and fatigue was the most serious side effect. Anorexia and weight loss, stomatitis, nausea and vomiting, diarrhea, and peripheral neuropathy were the other toxic effects. We conclude that MGBG has activity in NSCLC, especially in previously untreated patients, and further studies are indicated in that population.
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PMID:Phase II trial of methylglyoxal-bis-(guanylhydrazone) in non-small-cell lung cancer. 627 32

Twenty-six adult patients were entered in a phase I trial of carboplatin, a new cisplatin derivative with reduced potential for nephrotoxicity. All patients had solid tumors and the median World Health Organization performance score was 2 (0-3). Twelve patients had not received prior chemotherapy. The drug was administered as a 15-minute IV infusion, without pre- or posthydration, at daily doses of 40-125 mg/m2 for five consecutive days. Antiemetics were given only if needed. Thrombocytopenia and neutropenia were dose related and dose limiting. One patient died from septic shock at the highest dose level. Nonhemolytic anemia was also encountered. Nausea and vomiting were experienced by most patients but gastrointestinal intolerance was severe in only two patients. One patient had hypercreatininemia, which was minor and rapidly reversible. Other toxic effects consisted of negligible fatigue, paresthesia, pruritus, local pain, stomatitis, headache, and alopecia. Although none of the patients achieved a partial or complete response, antitumor effect was strongly suggested in two patients with thyroid and cervix cancer, respectively. Carboplatin is an attractive candidate for phase II trials. In good-risk patients, such trials could be initiated at a daily dose of 100 mg/m2 for five consecutive days every five to six weeks.
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PMID:Phase I study of carboplatin given on a five-day intravenous schedule. 636 28

Marcellomycin is a new anthracycline that was proposed for clinical trials on the basis of experimental data suggesting reduced potential for hematologic and cardiac toxicity as compared to conventional anthracyclines. This phase I trial was designed to determine the maximum tolerated dose of marcellomycin at a single-dose schedule. The drug was given as a 15-to 30-min i.v. injection. Eighteen patients with a variety of solid tumors received a median of 2 courses (range: 1-5) at doses of 5-60 mg/m2. Myelosuppression was dose-limiting and somewhat unpredictable. It was characterized by early thrombocytopenia and late leukopenia. It occurred at doses greater than or equal to 40 mg/m2 and resulted in a few cases of infection and hemorrhage. Nausea, vomiting and stomatitis were frequent and occasionally severe. Other common non-hematological toxic effects consisted of local phlebitis and fatigue. Electrocardiographic changes were also encountered. Hair loss was rare and negligible. No antitumor activity could be detected. It appears that phase II trials should be preferably restricted to ambulatory patients and that a dose schedule of 50 mg/m2 repeated every 3 weeks may be proposed for this favorable patient population.
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PMID:Clinical phase I trial of marcellomycin with a single-dose schedule. 668 82

Marcellomycin, a new anthracycline antibiotic, was administered intravenously on a weekly schedule to 22 patients with advanced malignant solid tumors. Patients were treated at 6 dosage levels ranging from 5 to 30 mg/m2 weekly for 4 weeks. Courses were repeated after a 3-week rest period. Hematologic toxicity was dose-limiting but unpredictable. Of 10 patients treated with weekly doses of 27.5 mg/m2, 3 patients exhibited myelosuppression and 2 died in agranulocytosis. Moderate to severe nausea and vomiting occurred in 19 of 22 evaluable patients. Other toxic effects were non-acute and consisted of mild stomatitis, diarrhea, phlebitis and moderate fatigue in 1-3 patients each. In 17 patients evaluable for antitumor activity no partial or complete responses occurred. One patient with advanced breast cancer showed a mixed response. Marcellomycin given on a weekly dose schedule has unpredictable and erratic hematologic toxicity. The maximally tolerated dose appears to be between 27.5 and 30 mg/m2 weekly. However, no firm recommendations can be given for a dose level that results in tolerable, predictable and reversible toxicity.
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PMID:A phase I trial of marcellomycin with a weekly dose schedule. 668 83

53 patients with advanced and measurable cancerr were treated with vindesine in doses of 3 mg/m2 (pretreated) and 4 mg/m2 (non pretreated) i.v. once weekly. 48 patients are evaluable for response: of 14 patients with squamous cell carcinoma of the lung, 1 partial remission (PR), 1 minor response (MR) and 1 no change (NC) were observed. In 5 patients with large cell carcinoma of the lung: 1 NC. In 3 with adenocarcinoma of the lung: 1 MR. One patient with nasopharyngeal carcinoma had progressive disease. Stable disease was observed in a patient with carcinoma of the tongue and in a patient with adenocarcinoma of the esophagus. Four patients with colorectal carcinoma had progressive disease. One MR was observed in a patient with breast cancer, while all of the other 3 patients had progressive disease. One carcinoma of the penis was stable. One MR was observed in a patient with Hodgkin's disease. One PR was observed in a case with no-Hodgkin's lymphoma. A patient with acute leukemia had progressive disease. Among 9 patients with malignant melanoma, 3 had an MR and 1 patient had stable disease. A patient with fibrosarcoma had progressive disease. Observed toxicity included leukopenia, thrombocytopenia, anemia, paresthesias, constipation, jaw pain, nausea, stomatitis, alopecia, loss of taste, pruritus and skin rash, weakness and fatigue.
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PMID:[Phase-II-study with vindesine (desacetyl-vinblastine-amide-sulfate) in advanced malignant diseases]. 742 51

Pyrazine diazohydroxide (NSC-361456) was identified as an active congener of pyridine 2-diazohydroxide with enhanced stability under physiologic conditions. In this phase I study, 35 patients with advanced cancer received 62 courses of PZDH administered intravenously every 3 weeks at doses ranging from 15-608 mg/m2. The dose-limiting toxicity was myelosuppression and the maximal tolerated dose was 487 mg/m2. Hematologic toxicity was delayed and prolonged with median time to recovery about 5 weeks. Mild gastrointestinal toxicity in the form of nausea and vomiting was fairly common. Ondansetron was effective in reducing nausea and vomiting at higher dose levels. Other less common reactions included stomatitis, diarrhea, fatigue, alopecia, and mild abnormalities of renal function and hepatic enzymes. PZDH pharmacokinetics were characterized in 16 patients who received doses of 100-608 mg/m2. Plasma elimination was fit to one (12/16) or two (4/16) compartment model with a mean k10 half-life of 11.5 min. Clearance was dose dependent. Hematologic toxicity was related to PZDH dose, AUC and peak plasma concentration. The sigmoidal relationships between hematologic toxicity and AUC or peak plasma concentration were well described by the Hill equation. There were no objective responses observed in this study. Based on this study, the recommended dose for phase II evaluation of PZDH using this schedule is 390 mg/m2.
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PMID:Pyrazine diazohydroxide (NSC-361456). Phase I clinical and pharmacokinetic studies. 789 39

Piroxantrone, a synthetic intercalating agent, was studied in patients with advanced, measurable gastric adenocarcinoma who had not received prior chemotherapy. The starting piroxantrone dose was 150 mg/m2 given intravenously over 1 hour on day 1 and repeated every 21 days. Response and toxicity could be evaluated in 15 patients. No complete, partial, or minor responses were observed. Toxic effects included granulocytopenia, anemia, vomiting, nausea, anorexia, fatigue, stomatitis, alopecia, hyperbilirubinemia, and increased alkaline phosphatase levels. At the stated dose and schedule, piroxantrone does not possess significant activity against advanced gastric cancer.
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PMID:Phase II trial of piroxantrone in metastatic gastric adenocarcinoma. 789 47

We conducted a multi-institutional (33 institutes), late phase II study with a 21-consecutive-day oral administration of etoposide for malignant lymphoma. Patient entry criteria were either those refractory to standard therapies or those for whom no appropriate therapy was available. A once-daily dose of 50 mg/body was administered for 21 consecutive days. Of the evaluable 83 among 88 entry patients, the overall response rate was 53.0% (44/83), including 10 CR; 52.5% (42/80, 9 CR) with non-Hodgkin's lymphoma and 100% (2/2, 1 CR) with Hodgkin's disease. Regarding abnormal laboratory findings, myelosuppression was observed; the incidence rates of leukopenia (23.3% with Grade 3), neutropenia (32.6%), hemoglobin decrease (17.4%) and thrombocytopenia (4.7%) were 70.9%, 65.1%, 54.7% and 19.8%, respectively. Major adverse reactions and their incidence were: anorexia 43.0%, alopecia 37.2%, nausea/vomiting 32.6%, fatigue 18.6%, stomatitis 15.1%, fever 7.0% and diarrhea 5.8%. Therefore, a 21-consecutive-day oral administration of 50 mg/body/day or 75 mg/body/day appears to be effective for the treatment of malignant lymphoma.
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PMID:[Late phase II study with 21-consecutive-day oral administration of etoposide for malignant lymphoma]. 799 16

A multi-institutional early phase II study of KW-2307 (vinorelbine), a new vinca alkaloid derivative, in advanced or recurrent breast cancer was conducted in 15 nationwide hospitals. KW-2307 was intravenously administered once weekly at doses of 15 to 25 mg/m2. Sixty-five among the enrolled 69 patients were eligible. Response rates were 11.8% (2/17) with 15 mg/m2, 28.0% (7/25) with 20 mg/m2 and 17.4% (4/23) with 25 mg/m2, and the overall response rate was 20.0%. Once-weekly intravenous administration of 20 mg/m2 was estimated to be the optimal dose of KW-2307 from the results. The major side effect was leucopenia, which was the dose-limiting factor in this study. Other subjective or objective side effects included anorexia, nausea-vomiting, phlebitis, fever, general fatigue and stomatitis, but none of them was serious.
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PMID:[Early phase II study of KW-2307 in advanced or recurrent breast cancer. KW-2307 Cooperative Study Group (Breast Cancer Section]. 818 37

A multi-institutional late phase II study of KW-2307 (vinorelbine), a new vinca alkaloid derivative, in advanced or recurrent breast cancer was conducted in 26 nationwide hospitals. KW-2307 was intravenously administered at a dose of 20 mg/m2 once weekly. Eighty among the enrolled 82 patients were eligible. The overall response rate was 30.0% (24/80) with 4 CR, 20 PR, 5 MR, 22 NC, 17 PD and 12 unevaluable patients. The major side effect was leucopenia, which was the dose-limiting factor in this study. Other subjective or objective side effects included general fatigue, nausea-vomiting, anorexia, paresthesia, fever and stomatitis, but none of them was serious.
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PMID:[Late phase II study of KW-2307 in advanced or recurrent breast cancer. KW-2307 Cooperative Study Group (Breast Cancer Section)]. 818 38


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