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)

Capecitabine is a fluoropyrimidine carbamate capable of exploiting the high concentrations of thymidine phosphorylase in tumor tissue to achieve activation preferentially at the tumor site. Thymidine phosphorylase activity is high in renal cell carcinoma tissue. Interferon alfa has been proved to be the agent for standard therapy in metastatic renal cell carcinoma. The purpose of the study was to assess the efficacy and toxicity of combining capecitabine and interferon alfa-2A in patients with advanced renal cell carcinoma. Twenty-five patients with advanced renal cell carcinoma and no prior systemic therapy were treated with the combination of capecitabine at a dose of 1,250 mg/m2 twice daily for 2 weeks after every 21 days and interferon alfa-2A 6 million U three times a week. The overall response rate was 24.0% (95% CI, 9.4-45.1%), from 6 responded patients 5 had partial responses and 1 complete response. Stable disease status was achieved in 9 patients (36.0% with 95% CI 18.0-57.5%). The median survival time was 248 days (95% CI, 173-265 days). The median time to progression was 126 days (95% CI, 49-165 days). Grade 3-4 toxicities occurred in 12 patients and included fatigue (33.3%), nausea, hand-foot syndrome (both 12.5%), anorexia (8.3%), vomiting, anemia and neutropenia (all 4.2%). The capecitabine and interferon alfa-2A combination has clinical activity and an acceptable toxicity profile in patients with metastatic renal cell carcinoma. The importance of adding capecitabine to interferon alfa needs to be confirmed in a randomized trial.
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PMID:Combination therapy with capecitabine and interferon alfa-2A in patients with advanced renal cell carcinoma: a phase II study. 1546 18

TAS-102 is a novel formulation of the fluorinated pyrimidine analogue trifluorothymidine (FTD) with an inhibitor of thymidine phosphorylase. The purpose of this study was to determine the MTD and DLT for TAS-102 administered three times a day on days 1-5 and 8-12 every 4 weeks. Fifteen patients were enrolled with two patients experiencing dose-limiting fatigue and granulocytopenia at the first dose level (80 mg/m2/day). Granulocytopenia was the primary toxicity: 7 patients experienced grade 3 or 4 granulocytopenia with the first course. No responses were noted, but nine patients demonstrated prolonged stable disease in this heavily pretreated 5-FU refractory population.
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PMID:Phase I clinical study of three times a day oral administration of TAS-102 in patients with solid tumors. 1879 63

Trifluridine/tipiracil (TAS-102) is a new oral combination therapy approved by the US Food and Drug Administration for the treatment of patients with metastatic colorectal cancer who are refractory to or intolerant of standard chemotherapy. This agent consists of a thymidine-based nucleoside analogue (trifluridine) and a thymidine phosphorylase inhibitor (tipiracil), which is included to reduce the degradative breakdown of trifluridine. In the phase III Randomized, double-blind, phase III Study of TAS-102 plus best supportive care [BSC] versus placebo plus BSC in patients with metastatic colorectal cancer [CRC] refractory to standard chemotherapies (RECOURSE) trial, trifluridine/tipiracil showed significant improvement in overall survival compared with placebo. Trifluridine/tipiracil is administered at a 35 mg/m2 dose orally twice daily in a 28-day cycle consisting of 5 treatment days/2 rest days for 2 weeks followed by a rest period of 2 weeks. Because trifluridine/tipiracil is a completely oral chemotherapy regimen, patient adherence to treatment is an important consideration. It is also critical to have strategies in place for managing toxicities, because side effects might have a negative effect on patient adherence. The most frequent adverse events reported in patients with metastatic colorectal cancer receiving trifluridine/tipiracil in the phase III RECOURSE trial were myelosuppression, nausea/vomiting, diarrhea, decreased appetite, and fatigue. In this review we aim to provide clinicians with practical recommendations for facilitating patient adherence to oral chemotherapy, managing trifluridine/tipiracil dosing, and address the most common adverse events in patients who receive trifluridine/tipiracil therapy.
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PMID:Adherence, Dosing, and Managing Toxicities With Trifluridine/Tipiracil (TAS-102). 2824 61