Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00201 (GEO)
 1,562 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

The treatment of advanced pancreatic carcinoma has been viewed with pessimism. Because of the lack of activity of commonly used agents, there is no consensus regarding a standard chemotherapy regimen. Assessment of response is neither uniform nor reproducible. Debilitating tumor-related symptoms, including pain, anorexia, weight loss, and impaired performance status, are common. Many studies have failed to evaluate the palliative benefit of treatments, although many patients consider such benefit to be of the utmost importance. Tools have been developed to uniformly assess tumor-related symptoms, and the concept of clinical benefit response has been developed as an end point to quantify symptomatic improvement utilizing these tools. Clinical benefit response incorporates palliative measures, such as pain control, analgesic consumption, performance status, and weight gain. In early phase I and II trials, gemcitabine (Gemzar) has shown activity in patients with chemotherapynaive advanced pancreatic carcinoma. In addition to producing some responses and symptomatic benefit, gemcitabine has a favorable toxicity profile. Two recent trials using clinical benefit response as the primary end point have demonstrated that gemcitabine significantly improves disease-related symptoms in approximately one-quarter of patients. These trials also showed improved survival with gemcitabine, as compared with fluorouracil. Additional studies are required to fully assess the role of gemcitabine in both adjuvant and advanced disease settings.
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PMID:Clinical experience with gemcitabine in pancreatic carcinoma. 939 63

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