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)

LY188011 (Gemcitabine hydrochloride) is a new derivative of deoxycytidine. Phase I study was carried out by a cooperative study group. LY188011 was administered weekly for 3 consecutive weeks starting with an initial dose of 60 mg/m2 (1n) and then increasing the dosage to 1,000 mg/m2 (16.7n). Dose limiting factor was found to be myelosuppression (decreases of WBC, neutrophils and platelet), and MTD was considered to be 1,000 mg/m2. The nadir of WBC and platelet were observed after about 1-3 weeks. It took 1-2 weeks for their recovery. Other adverse reactions included fever, fatigue, anorexia, nausea/vomiting, anemia and transient elevations of GOT and GPT. However, those adverse reactions were mild. T1/2 rho of plasma concentration was about 19 min and the C5min was dependent on the dose. Anti-cancer effects were observed in one gastric cancer and two colon cancer patients. It is recommended that the dosing schedule for an early phase II study is 800 mg/m2 weekly for 3 weeks with 1 week of rest as one cycle, in multiple cycles.
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PMID:[LY188011 phase I study. Research Group of Gemcitabine (LY188011)]. 868 15

In a randomized phase III trial, 343 patients with advanced non-small cell lung cancer aged <or=70 years with good performance status received a new triplet regimen consisting of cisplatin at 50 mg/m(2), gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) at 1,000 mg/m(2), and vinorelbine at 25 mg/m(2) on days 1 and 8 every 3 weeks (PGV); a doublet of cisplatin at 100 mg/m(2) on day 1 and gemcitabine at 1,000 mg/m(2) on days 1, 8, and 15 every 4 weeks (PG); or a newly developed triplet combination of cisplatin at 50 mg/m(2), gemcitabine at 1,000 mg/m(2), and paclitaxel at 125 mg/m(2) (over 1 hour) on days 1 and 8 every 3 weeks (PGT). Response rates were 44% in the PGV group, 48% in the PGT group, and 28% in the PG group (P < .02 for both PGV and PGT v PG). Median survival durations were significantly increased in both the PGV and PGT groups compared with the PG group (51 weeks for both v 38 weeks; P < .05 for both). Times to disease progression were increased in both the PGV (24 weeks) and PGT (29 weeks) groups compared with the PG group (19 weeks) (PGT v PG; P < .002). Both triple-agent combinations were well tolerated. Among hematologic toxicities, severe thrombocytopenia was more common in the PG arm than in the PGT group. Severe vomiting was more common in the PG arm than in either triplet group, whereas mild neuropathy was more common in the triple-agent arms and grade 3 fatigue was more common in the PGT group than in the PG arm. In summary, the new PGV and PGT triplet regimens were associated with improved outcome in patients with advanced non-small cell lung cancer with good performance status, without an increase in major toxicity. Semin Oncol 28 (suppl 7):7-10.
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PMID:Phase III trial of cisplatin/gemcitabine with or without vinorelbine or paclitaxel in advanced non-small cell lung cancer. 1137 45

Both paclitaxel and gemcitabine (Gemzar) have shown activity and manageable toxicity when used as single agents in heavily pretreated patients with metastatic breast cancer. This phase II study evaluated their use in combination for metastatic breast cancer patients whose disease recurred or progressed following treatment with anthracycline-containing regimens. Twenty-nine patients ranging from 32 to 68 years of age received paclitaxel at 175 mg/m2 i.v. over 3 hours on day 1 and gemcitabine at 1,000 mg/m2 i.v. on days 1, 8, and 15 every 28 days. Because of unacceptable thrombocytopenia in the first five patients, the gemcitabine schedule was changed to days 1 and 8 of a 21-day cycle for the remainder of the study. All 29 patients were evaluable for response and toxicity. Seventeen patients (59%) were considered truly anthracycline- or anthracenedione-refractory. A total of 137 cycles (median: 4 per patient) were administered. The regimen was well tolerated. Grade 3/4 thrombocytopenia was observed in 5 (18.5%) of the first 27 cycles and in 6 (5.4%) of the 110 cycles following dosage reduction (P = .04). Five patients had grade 1 and two patients had grade 3 neuropathy. Eight patients had grade 3 neutropenia, two had grade 4 neutropenia with fever at the higher dosage, and eight had grade 1/2 myalgia and fatigue. Five patients (17%) had a complete response and 11 (38%) a partial response, yielding an objective response rate of 55% (95% confidence interval = 36%-73%). Six patients (20.7%) had stable disease. Median response duration was 8 months (range: 4-26 months), and median overall survival was 12 months (range: 4-48+ months). Survival at 1, 2, 3, and 4 years was 45%, 30%, 20%, and 10%, respectively. The combination of paclitaxel on day 1 with gemcitabine on days 1 and 8 of a 21-day cycle appears to have promising activity in heavily pretreated patients with metastatic breast cancer. Phase III trials comparing this promising doublet to paclitaxel monotherapy and to other chemotherapeutic strategies for advanced breast cancer will clarify the role of this regimen.
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PMID:Paclitaxel and gemcitabine as salvage treatment in metastatic breast cancer. 1476 2

Data from a clinical study of 86 pancreatic cancer patients with involuntary, significant weight loss (cachexia) were used to explore the relationship between patient-reported outcomes (PROs) and survival. In all, 28 pancreatic cancer patients with cachexia were given gemcitabine (Gemzar) plus 3 mg/kg of infliximab (Remicade), 28 were given gemcitabine plus 5 mg/kg of infliximab, and 30 were given gemcitabine plus placebo in a double-blinded, phase II, multicenter trial. PRO endpoints included scores from the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Functional Assessment of Anorexia/ Cachexia Therapy (FAACT), Brief Pain Inventory (BPI), and the Short-Form 36 general health survey (SF-36). Population mean scores at baseline indicated fatigue problems (FACIT-F), nutritional health issues (FAACT), and mild-to-moderate pain (BPI "worst pain" score). Baseline normalized SF-36 values for physical functioning, vitality, and mental health indicated substantial impairment. Baseline fatigue and physical-functioning scores predicted survival as well as, or better than, baseline Karnofsky Performance Status or hemoglobin level. A cut-point in the FACIT-F score (median < or = 30) strongly predicted mortality; patients with greater fatigue had a lower median overall survival than did those with less fatigue. These findings supported several features of an a priori clinical-benefit model. Patient-reported fatigue provided powerful prognostic information; tracking of this symptom may be useful for treatment planning and medical monitoring of advanced-stage pancreatic cancer patients with cachexia. These results must be confirmed by larger trials.
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PMID:The prognostic significance of patient-reported outcomes in pancreatic cancer cachexia. 1872 39