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)

The palliation of symptoms and improvement of quality of life are important aspects of therapy in patients with incurable metastatic cancer. This article describes the preliminary results of a phase I study of uracil and tegafur, an orally available fluorouracil (5-FU) derivative combined with oral leucovorin plus weekly intravenous paclitaxel. While the daily oral dose of UFT is fixed at 300 mg/m2 plus 90 mg leucovorin on days 1 to 28, paclitaxel is escalated in 10 mg/m2 steps starting with 50 mg/m2 weekly as a 1-hour infusion. To date, 26 patients with a median age of 57 years have been entered into the protocol and have received a median 2.2 cycles of therapy. Dose level 4 (paclitaxel 80 mg/m2) has been recently completed. Major dose-limiting toxicities were fatigue syndrome (two patients) and diarrhea (five patients). Preliminary responses have been observed in three of 14 currently evaluable patients. This protocol is taking the development of protracted 5-FU administration--given orally as UFT--in combination with paclitaxel one step further, using paclitaxel in a dose-dense, weekly schedule. It is hoped that an active regimen for the outpatient treatment of solid tumors will be developed.
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PMID:UFT/leucovorin plus weekly paclitaxel in the treatment of solid tumors. 1109 97

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

Most neoplasms arising from the thymic epithelium are considered to be 'thymomas', which are composed of cytologically benign, neoplastic epithelial cells and nonneoplastic lymphocytes. In contrast, thymic epithelial neoplasms displaying cytologically malignant features have recently been classified as thymic carcinomas of various types of histology. However, primary thymic adenocarcinoma is extremely rare and only four cases of it have been reported in the literature. We report a rare case of primary thymic adenocarcinoma of 4-year complete remission with concurrent chemoradiotherapy followed by surgery. A 61-year-old Japanese man was referred to us complaining of facial edema and general fatigue. Computed tomography scans revealed a huge mass in the anterior mediastinum obstructing the superior vena cava. He was diagnosed with thymic adenocarcinoma on needle biopsy. He was treated with induction chemoradiotherapy consisting of cisplatin, 5-FU and concurrent thoracic radiation, which yielded a partial response. He then underwent surgical resection of the remaining mass. However, pathologic examination of the resected mass revealed no malignant cells. The patient is doing well without symptoms or signs of relapse 53 months after diagnosis.
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PMID:Successful treatment with concurrent chemoradiotherapy followed by surgery for a patient with thymic adenocarcinoma. 1172 16

We retrospectively evaluated the efficacy of chemotherapy regarding symptom control, toxicity and discharge rate in 39 patients with gastric or colorectal cancer. Treatment consisted of TS-1 (n = 16), TS-1 + CPT-11 (n = 8), CDDP + CPT-11 (n = 5), paclitaxel (n = 8) and MTX + 5-FU (n = 4) for gastric cancer and 5-FU + l-leucovirin (n = 6), 5-FU + CPT-11 (n = 5), MMC + CPT-11 (n = 8) and 5-FU protracted continuous infusion (n = 5) for colorectal cancer. The rates of symptom improvement were the following: pain 60% (10/15), general fatigue 56% (5/9) and abdominal fullness 53% (8/15). 87% (34/39) of the patients were discharged from hospital and continued chemotherapy as outpatients grade 3 toxicities were the following: anemia 10.3%, nausea and/or vomiting 7.7%, diarrhea 5.1%. There was no treatment related death. The rates of outpatient based treatment duration improvement were the following: gastric cancer: 47.6%, colorectal cancer: 72%. These data suggest that these treatments for gastric and colorectal cancer are safe and improve the patients' QOL.
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PMID:[Effectiveness of chemotherapy for outpatients with gastric or colorectal cancer]. 1253 32

5-Fluorouracil-based combination chemotherapy is commonly used in patients with advanced gastric cancer, but results with such therapy are fairly modest. Evaluation of newer agents is therefore required in this disease. Paclitaxel has shown promising activity as a single agent in gastric cancer. In vitro, paclitaxel exhibits sequence-dependent synergy with platinum compounds against gastric cancer. This study was conducted to evaluate the efficacy and toxicity of combination carboplatin and paclitaxel in patients with advanced gastric cancer. Twenty-seven patients with measurable or evaluable advanced gastric cancer were enrolled on the study from April 1996 to July 2000. Patients were treated with paclitaxel 200 mg/m intravenously during 3 hours followed by carboplatin at projected area under the curve 5 mg x h x ml (as per the Calvert formula). Twenty-six patients were assessable for toxicity, and 25 patients were assessable for objective response. Nine of the 27 enrolled patients had a major response for an objective response rate of 33% (95% CI 0.17-0.54) by intention-to-treat analysis. The median response duration was 4.9 months (95% CI 2.8-7.3), and median survival was 7.5 months. The 1-year survival rate was 23%. One hundred seventeen courses were administered with a median of four courses per patient administered. The major toxicity was neutropenia, with grade III to IV neutropenia observed in 9 patients (33%) and neutropenic fever in only 1 patient. Grade III peripheral neuropathy developed in two patients, and grade III myalgia and grade III fatigue developed in one patient each. There were no treatment-related deaths. The combination of carboplatin and paclitaxel is a highly tolerable, regimen with activity comparable to that of other regimens in advanced gastric cancer. This regimen needs to be further evaluated in combination with other agents and as a component of multimodality therapy in gastric cancer.
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PMID:Phase II study of paclitaxel and carboplatin in patients with advanced gastric cancer. 1257 22

Ras oncogenes (K-, H- and N-ras) are known to be involved in signal transduction pathways regulating cell growth and differentiation in many human cancers. These proteins are synthesized as a cytosolic precursor that ultimately localizes to the inner plasma membrane. This process is initiated by the attachment of a farnesyl moiety to the protein and is catalysed by the farnesyl transferase. Since activated (mutated) ras oncogenes have been shown to be essential for the malignant phenotype in many tumors, farnesyl transferase inhibitors (FTIs) have emerged as a novel class of antineoplastic agents. Four FTIs are currently in clinical trials. Two of these agents, R-115777 and SCH-66336, are orally active heterocyclic compounds and already in phase II/III studies. Preliminary results of R-115777 or SCH-66336 in combination with gemcitabine or 5-FU/FA in patients with advanced pancreatic carcinomas have been reported. The dose-limiting toxicity was neutropenia, nausea, diarrhea and fatigue. The recommended doses for phase II studies were 200 mg R-115777 or 2 x 200 mg SCH-66336. Durable objective partial responses were noted in several patients. Furthermore, the FTIs were found to be well tolerated. Ongoing phase III studies in patients with advanced pancreatic cancers will determine the extent of clinical activity and whether these agents can be used as single agents for the treatment of pancreatic carcinomas or have to be used in combination with other cytostatic drugs. In addition, it remains to be clarified whether FTIs may sensitize drug-resistant cancers following conventional chemotherapy.
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PMID:Farnesyltransferase inhibitors--a novel approach in the treatment of advanced pancreatic carcinomas. 1282 Mar 5

The purpose of this report is to summarize information on oxaliplatin, a drug recently approved by the U.S. Food and Drug Administration. Information provided includes regulatory history, study design, efficacy and safety results, and pertinent literature references. A single, multicenter, randomized trial, enrolling 463 patients with metastatic colorectal carcinoma whose disease had recurred or progressed during or within 6 months of completion of therapy with the combination of bolus 5-fluorouracil (FU)/leucovorin (LV) and irinotecan, was submitted. Study arms included infusional 5-FU/LV alone (arm A), oxaliplatin alone (arm B), and the combination of oxaliplatin and infusional 5-FU/LV(arm C). Oxaliplatin, at a dose of 85 mg/m2, was administered to patients in arms B and C intravenously over 2 hours in 250-500 ml of dextrose 5% in water (D5W) on day 1 only. A 200-mg/m2 dose of LV was administered simultaneously to arm C patients, in a separate bag using a Y-line, or alone to arm A patients, by i.v. infusion, over 2 hours. 5-FU was then administered to arms A and C patients, first as a bolus injection over 2-4 minutes at a dose of 400 mg/m2, then as a continuous infusion in 500 ml of D5W over 22 hours at a dose of 600 mg/m2. LV was repeated on day 2 of the cycle (arms A and C) followed by a 400-mg/m2 5-FU bolus and a 600-mg/m2 22-hour infusion. Treatment was repeated every 2 weeks. Response rate was the prespecified end point for accelerated approval. Time to progression (TTP) was a secondary end point. The prespecified primary comparison was between the 5-FU/LV regimen and the 5-FU/LV/ oxaliplatin combination regimen. The three arms were well balanced for patient prognostic factors. There were no complete responders. The partial response rates were 0%, 1%, and 9% for the 5-FU/LV, oxaliplatin, and oxaliplatin plus 5-FU/LV treatments, respectively (p = 0.0002, arm C versus arm A). The median times to radiographic tumor progression, based on available radiographs, were 2.7 months, 1.6 months, and 4.6 months, respectively (p < 0.0001, arm C versus arm A). Common adverse events associated with the combination treatment included peripheral neuropathy, fatigue, diarrhea, nausea, vomiting, stomatitis, and abdominal pain. Neutropenia was the major hematologic toxicity. Adverse events were similar in men and women and in patients <65 and > or =65 years of age, but older patients may have been more susceptible to dehydration, diarrhea, hypokalemia, and fatigue. Oxaliplatin in combination with infusional 5-FU/LV was approved for the treatment of patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed during or within 6 months of completion of first-line therapy with the combination of bolus 5-FU/LV and irinotecan. Approval was based on response rate and on an interim analysis of TTP. No results are available, at this time, that demonstrate a clinical benefit, such as improvement in disease-related symptoms or survival.
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PMID:FDA drug approval summaries: oxaliplatin. 1475 10

Colorectal cancers (CRC) express the epidermal growth factor receptor (EGF-R), a type I transmembrane receptor with tyrosine kinase activity. EGF-R signaling inhibition is a promising target for cancer therapy. ZD1839 (Iressa, AstraZeneca) and OSI-774 (Tarceva, Roche) are small molecular weight molecules with selective and reversible tyrosine kinase inhibition properties directed to EGF-R. Orally administered, these molecules induce sustained tumor stabilizations in previously treated metastatic CRC patients. The most frequent treatment-related toxicities are fatigue, diarrhea and acne-like follicular rash. The addition in the clinic of 5-FU, lOHP or CPT-11 to ZD1839 or OSI-774 does not seem to increase the own toxicity of each cytotoxic agents. Cetuximab (Erbitux, Merck) is an intravenously administered humanized monoclonal antibody which bind with high affinity with the extracellular domain of the EGF-R. The most frequent treatment-related toxicities are diarrhea, fatigue, nausea and cutaneous toxicity (allergic or acne-like follicular rashes, folliculitis). Most, if not all of these adverse events are mild. Partial responses were observed with cetuximab either alone (RR: 10%) or in combination with CPT-11 (RR: 22%) in patients with CPT-11 refractory advanced CRC which expressed EGF-R. The combination of cetuximab to folinic acid, 5-FU and CPT-11 seems tolerable at the cost of a slight increase of severe diarrhea and neutropenia. Finally, the promising activity of these EGF-R inhibitors has to be confirmed throughout randomized studies.
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PMID:[Inhibitors of epidermal growth factor receptor and colorectal cancer]. 1476 44

A 75-year-old man was admitted to our hospital complaining of gastric fatigue. Endoscope and CT scan revealed type 3 gastric cancer with paraaortic lymph nodal metastasis. Histological examination of the endoscopic biopsy revealed poorly differentiated adenocarcinoma. A blood examination and bone marrow biopsy revealed DIC causing bone marrow carcinosis. Chemotherapy with sequential therapy consisting of MTX and 5-FU was performed. Stretch of the fold and flatness of the ulcer were obtained against the gastric primary lesion observed endoscopically. Complete response was obtained against the lymph node around the abdominal aorta. Reduction of low back pain and DIC were observed. He was thus able to be discharged and sequential therapy was performed again over 2 months in outpatient care.
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PMID:[A case of advanced gastric cancer with DIC treated by sequential MTX and 5-FU]. 1504 48

This study investigated the efficacy and tolerability of ZD9331 as second- or third-line treatment for patients with advanced colorectal cancer (aCRC). One hundred patients were recruited to the study: 45 in group 1 (failed first-line 5-FU-based regimen) and 55 in group 2 (failed first-line 5-FU-based regimen and second-line irinotecan). Patients received ZD9331 as a 30-minute intravenous infusion on days 1 and 8 of a 3-week cycle, and treatment continued until disease progression (PD) or withdrawal. After a median of 4 cycles of treatment, there were no objective responses in group 1 (N = 37), 25 (67.6%) patients had a best overall response of stable disease (SD), and 12 (32.4%) had PD. After a median of 3 cycles of treatment, there were 2 (4.5%) partial responses in group 2 (N = 44), 21 (47.7%) patients had a best overall response of SD, 20 (45.4%) had PD, and 1 (2.3%) had clinical progression. At data cut-off, 59.5% and 77.3% of patients in groups 1 and 2, respectively, had PD. The main adverse events were neutropenia (69%), fatigue (53%), nausea (46%), and diarrhea (40%), and most (72.3%) were grade I/II. ZD9331 demonstrated minimal antitumor activity, and manageable toxicity, in the second- or third-line treatment of aCRC.
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PMID:ZD9331 as second- or third-line therapy in patients with advanced colorectal cancer: a phase II multicenter trial. 1528 25


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