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 phase I trial of piritrexim was conducted by use of a prolonged, low-dose oral schedule. A number of different regimens were tested, including daily dosing for 21 days followed by 7 days of no drug therapy; continuous dosing; and daily dosing for 5 of 7 days for 3 consecutive weeks followed by a week of rest. Dose escalation was accomplished by increasing the dosing frequency from once a day to twice a day and then to three times a day and by increasing the number of days of administration. Fifty-one patients with advanced cancer were entered in the study. One hundred twenty-four (96%) of 129 courses were considered assessable. Myelosuppression proved to be the dose-limiting toxic effect. Other toxic effects included stomatitis, nausea and vomiting, anorexia, diarrhea, skin rash, fatigue, and elevation of liver transaminase levels. Antitumor activity was observed in patients with melanoma and bladder cancer, and disease stabilization occurred in those with sarcoma and pheochromocytoma. The recommended dosing schedule for phase II clinical trials is 25 mg three times a day for 5 days for 3 consecutive weeks followed by 1 week of no drug therapy.
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PMID:Phase I trial of piritrexim capsules using prolonged, low-dose oral administration for the treatment of advanced malignancies. 198 18

A questionnaire, filled in by the patient, was used to assess the quality of life of 65 patients with previously untreated T2-T4 NX MO bladder cancer and of 67 patients with hormone-resistant prostatic cancer. This study examines the initial questionnaire filled in before any nonsurgical treatment had been started in the patients referred to an oncological ward. The aim was to identify domains in which distress was frequent, in the hope of indicating where treatment directed forward improving the patients' quality of life should be directed. The questionnaires yielded reliable and valid data. Among bladder cancer patients micturition disturbances and sexual problems dominated. Bone pain, fatigue, sexual disturbances and interruption of social relationships were the most frequent and most severe complaints of prostatic cancer patients. It was concluded that routine quality of life evaluation by self-assessment questionnaires is possible in a clinical ward provided some assistance by the nursing staff is available. Future treatment in patients for whom palliation is the main goal of therapy should be concentrated on improving the quality of life in areas where distress is evident. The effect of treatment on quality of life could be monitored by similar questionnaires.
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PMID:Quality of life in patients with muscle-infiltrating bladder cancer and hormone-resistant prostatic cancer. 247 17

rTNF was administered to 28 patients with advanced metastatic cancers by continuous intravenous infusion for 5 consecutive days every 2 weeks. The dose levels were 30, 40, 70, 110, 180 and 290 micrograms/M2/day. Groups of 3 patients were started at each successive dose level and then on subsequent courses treated with the next dose level through 4 escalations as tolerated. Tumor types were: colon cancer 14; adenocarcinoma of unknown primary, 2; renal cancer, 2; leiomyosarcoma, 2; lung cancer, 1; prostate cancer, 1; thymona, 1; bladder cancer; 1; parotid, 1; Kaposi's sarcoma 2; ovarian 1. Toxicities included fever and chills (usually within the first 8 hours of infusion), fatigue, headache, decreased performance status, hypotension and CNS. All patients experienced leukopenia and thrombocytopenia within 24 hours or less after start of infusion with return of baseline by 72 hours after rTNF was stopped. The fall in these counts averaged 50% and was not dose related. No major changes in liver or renal function, coagulation or blood lipids were seen. Major dose limiting toxicities were fatigue, confusion, thrombocytopenia, seizures, hypotension and decreased performance status. NK cell activity measured against K562 target cells was augmented from about 30% target cell lysis to about 70% target cell lysis over the first 7 days of treatment. Two patients, both with metastatic colon cancer showed transient, objective tumor regression which did not qualify as a partial response. One patient with ovarian cancer had a stable partial response but progressed after 13 courses of treatment. Continuous infusion of TNF can be safely administered to patients with a maximum tolerated dose of only between 30 and 40 micrograms/M2/day.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A phase I trial of recombinant tumor necrosis factor (rTNF) administered by continuous intravenous infusion in patients with disseminated malignancy. 264 24

This data, along with data from other research studies, indicate that PDT is a promising new treatment for noninvasive bladder cancer. In the current study at Veterans Administration Medical Center, three of the four patients who received Thiotepa have had recurrences of their bladder tumors or positive urine cytology. The three patients who received PDT have not experienced any recurrences or positive urine cytology. Since we have been involved in this trial, we have developed some recommendations that other institutions may want to follow. The tip of the laser fiber is very bright. To decrease eye strain and fatigue, a lens cap with a green eye shield should be used on the cytoscope. All staff should wear green-colored safety eye glasses. This will protect their eyes from constant exposure to the intense incandescent radiation, and if the fiber should break, it would protect their eyes from the bright red color. With all the extra equipment such as ultrasound, power meters, light sources, and anesthesia equipment, it is important to avoid tripping over extension cords. The cords should be covered. Also, it is important not to bump into the equipment, which can happen because the OR is dark. At this time, the laser technician is the only person authorized at our medical center to operate the argon-pumped tunable dye laser. In the future, if more research programs are started or therapy is approved for other uses, additional personnel will be trained.
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PMID:Photodynamic laser therapy. A bladder cancer protocol. 304 9

A phase I study of VP was undertaken using the methods of a single (40 cases; range of dose levels 30-540 mg/m2) and 5-day (41 cases; range of dose levels 40-140 mg/m2/day) intravenous administration. The dose-limiting toxicity of VP was moderate to severe leukopenia. MTD was estimated to be 540 mg/m2 for a single and 140 mg/m2/day for 5-day administration. The median days to WBC nadir from the start of therapy and to recovery from reaching the nadir were 10 and 10.5 for single, and 15 and 7 for 5-day administration, respectively. Thrombocytopenia was less frequent and less pronounced than leukopenia. Mild gastrointestinal disturbances and alopecia were frequently observed. Transient hepatic dysfunction, fever, headache, fatigue, dyspnea, hypotension, and pain along the vein were also encountered in a small number of patients. There were no cases with renal, neurologic or cardiac toxicity. Objective tumor regression was seen in one case each of IBL(CR), bladder cancer, non-Hodgkin's lymphoma and ATL (PR). The post-infusion plasma decay of VP in 4 cases given 80-120 mg/m2 by a single administration was biphasic with t1/2 alpha ranging from 0.13 to 0.39 h and t1/2 beta ranging from 3.33 to 4.85 h. No accumulation of VP was found in plasma after five repeated daily doses. Doses of 360-480 mg/m2 by single and 80-100 mg/m2/day by 5-day administration repeated every 3 to 4 weeks can therefore be recommended for phase II studies in good-risk patients.
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PMID:[A phase I study of VP-16-213 (VP, etoposide) by single and 5-day intravenous administration]. 394 9

Recent results demonstrate an emerging role for paclitaxel in patients with urothelial-tract cancer and in patients with testicular cancer. Yielding response rates in the range of 40-50% as a single agent, paclitaxel is one of the most active drugs in metastatic bladder cancer. Ongoing trials of paclitaxel combination chemotherapy with cisplatin or cisplatin and ifosfamide demonstrate substantial objective remission rates above 70% and, in addition, a high range of complete responses. Thus, paclitaxel appears to be an important drug when used as part of first-line combination chemotherapy for metastatic bladder cancer. Ongoing clinical trials focus on the combination of paclitaxel with cisplatin, ifosfamide, gemcytabine, and carboplatin. Furthermore, paclitaxel administration has been demonstrated to be easily applicable to patients with reduced renal function, requiring no dose reduction and producing no increase in toxicity. Future strategies will have to compare the most active paclitaxel combination regimen with first-line MVAC (methotrexate, vinblastine, adriamycin, cisplatin) chemotherapy. Finally, the role of paclitaxel combination regimens needs to be explored in the adjuvant and neoadjuvant setting in patients with bladder cancer. In testicular cancer, paclitaxel has initially been tested in patients with cisplatin-refractory disease. Among 4 consecutive trials involving a total of 83 patients a response rate of 26% has been observed using dose schedules varying from 3-h to 24-h infusions and doses ranging from 175 to 250 mg/m2. The major toxicities of paclitaxel include neutropenia, neurotoxicity, and fatigue syndrome. Currently, combinations of paclitaxel with cisplatin +/- ifosfamide are used as first- or second-line salvage therapy in patients with relapsed metastatic testicular cancer. The German Testicular Cancer Study Group uses a paclitaxel (Taxol, ifosfamide, cisplatin; TIP) combination regimen as salvage treatment. Following the TIP regimen and the application of granulocyte colony-stimulating factor (G-CSF), peripheral blood stem cells (PBSC) are harvested and the patients subsequently receive high-dose chemotherapy with PBSC rescue. Since only a few drugs have demonstrated substantial activity in cisplatin-refractory disease, paclitaxel will be used in early salvage strategies and, possibly, as first-line chemotherapy as a part of platinum-based combination regimens in patients with testicular cancer. Further trials confirming the important role of paclitaxel in this highly curable malignancy and a thorough investigation of its acute and long-term toxicity will be the future tasks.
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PMID:The role of paclitaxel in chemosensitive urological malignancies: current strategies in bladder cancer and testicular germ-cell tumors. 898 35

The prognosis in cases of inoperable advanced gall bladder cancer is poor. We report here a case of inoperable advanced gall bladder cancer that responded to treatment with continuous intra-arterial infusion of 5-FU and bolus injection of LV for biochemical modulation. The patient was an 81-year-old woman, who visited a nearby clinic with the chief complaints of general fatigue and right lateral abdominal pain. A mass lesion which occupied from the dorsal surface of the liver to the pancreatic head was found by ultrasonography, and she was referred to our hospital for further diagnosis and therapy. The diagnosis was advanced gall bladder cancer of Stage IVa (S2, N3, P0, H0, Hinf1, Dinf1). For the selective arterial infusion of anticancer drugs, the patient underwent intra-arterial cannulation into the common hepatic artery, with a connecting subcutaneous port for arterial infusion therapy. The treatment schedule for 5-FU and LV therapy consisted of continuous infusion of 5-FU of 333 mg/m2 for 72 hr and bolus injection of LV of 20 mg/m2 3 times at 24 hr intervals. This treatment was repeated every 2 weeks. No side effects were observed after the first administration during hospitalization, so the treatment was continued up to 17 times on an outpatient basis. A tumor response was seen in the primary lesion, No. 8 and No. 16 lymph node metastases. A partial response was observed for 13 months and the overall survival was 15 months. These findings may imply that treatment with intra-arterial infusion of 5-FU and LV can be an effective chemotherapy for prolongation of survival in patients with inoperable advanced gall bladder cancer.
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PMID:[A case of inoperable advanced gall bladder cancer responding to intra-arterial infusion of 5-fluorouracil (5-FU) and leucovorin (LV)]. 1132 87

An 84-year-old male was admitted to our hospital with complaints of leg edema and general fatigue. He had undergone transurethral resection of transitional cell bladder cancer, grade 3, pT1b, one year previously. The computed tomographic scan revealed a hypoattenuating bladder tumor, protruding extravesically. Laboratory examination showed remarkable leukocytosis of 46,900/mm3 in the peripheral blood and high value of granulocyte colony-stimulating factor (G-CSF) 226 pg/ml (normal: less than 30 pg/ml). The resection of the tumor (partial cystectomy) was performed. The histological diagnosis was transitional cell carcinoma, grade 3. The production of G-CSF was confirmed by immunohistochemical examination in the recurrent tumor and the surgical sample from the transurethral resection. The leukocyte count in the peripheral blood decreased to the normal range after surgery. But leukocytosis recurred one month postoperatively and the computed tomographic scan revealed intrapelvic tumor recurrence. He died due to drastic progression of recurrent tumor at three months postoperatively.
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PMID:[Bladder carcinoma producing granulocyte colony-stimulating factor (G-CSF): a case report]. 1149 1

Yondelis (ET-743) is a novel anticancer agent isolated from the marine ascidian Ecteinascidia turbinata. ET-743 possesses potent antitumour activity and a novel mechanism of action at the level of gene transcription. We conducted two sequential phase I dose escalation and pharmacokinetic studies of ET-743 given as a 1- or a 3-h intravenous (i.v.) infusion. Seventy-two adults with metastatic or advanced solid tumours received ET-743 in escalating doses between 50 and 1100 microg/m(2), initially as a 1-h infusion, and later at doses between 1000 and 1800 microg/m(2) as a 3-h infusion every 3 weeks. The maximum tolerated dose (MTD) of ET-743 was 1100 microg/m(2) for the 1-h infusion schedule and 1800 microg/m(2) when given as a 3-h infusion. Dose-limiting toxicities (DLTs) were fatigue, neutropenia and thrombocytopenia. Transient non-cumulatives grade 3-4 increase in transaminases (not considered DLT) and grades 3-4 nausea and vomiting were frequently observed. Other toxicities (maximum grade 3) included anaemia, increased lactate dehydrogenase (LDH), bilirubin and alkaline phosphatase serum levels, and phlebitis; there were no toxic deaths. One pCR (melanoma), CR (uterine leiomyosarcoma), one PR (colon stromal sarcoma) and a MR (37% tumour shrinkage, gastric stromal sarcoma) were observed. A further 9 patients with colorectal, mesothelioma, bile duct carcinoma and bladder cancer had SD which lasted for six or more treatment cycles. ET-743 pharmacokinetics were linear with the 3-h infusion schedule. The haematological and hepatic toxicities of ET-743 were dose-dependent and not cumulative. Based on the current trial, the recommended dose of ET-743 for phase II studies is 1650 microg/m(2) given as a 3-h infusion.
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PMID:Phase I and pharmacokinetic study of Yondelis (Ecteinascidin-743; ET-743) administered as an infusion over 1 h or 3 h every 21 days in patients with solid tumours. 1293 61

Clinical experiences of endotoxin removal using polymyxin B immobilized fiber column (PMX) in two septic shock patients are reported. Case 1: A 74-year-old man with bladder cancer received a total cystectomy and a ileal conduit 19 years before he was referred to our hospital with complaints of high fever and general fatigue. Physical examination and laboratory data revealed severe hypotension, and pyuria. Left hydronephrosis due to uretero-intestinal stenosis were observed on computed tompgraphy (CT). Under the diagnosis of septic shock, left nephrostomy were performed. Direct hemoperfusion using polymyxin B immobilized fiber column was carried out. Case 2: A 74-year-old woman referred to our hospital with complaints of abdominal pain. Physical examination and laboratory data revealed severe hypotension, and pyuria. Right hydronephrosis due to retroperitoneal fibrosis were observed on CT. Diagnoses of septic shock were made. After right nephrostomy were performed, direct hemoperfusion using polymyxinB immobilized fiber column was carried out.
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PMID:[Clinical experiences of endotoxin removal in urinary obstruction: report of two cases]. 1557 18


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