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 II trial of 5'-deoxy-5-fluorouridine (5'-DFUR), a new fluorinated pyrimidine analog which has been demonstrated to have potential superiority over 5-FU and tegafur for chemotherapy of murine tumors, was performed in patients with advanced non-small cell carcinoma of the lung and metastatic pulmonary tumors. 5'-DFUR at a dose of 800 mg/m2 was given per os every day for more than four weeks. None of 15 evaluable patients with non-small cell carcinoma of the lung and 15 evaluable patients with metastatic pulmonary tumors showed a complete or partial response. Toxic effects of 5'-DFUR included anorexia (29%), diarrhea (26%), nausea (23%), vomiting (10%), leukocytopenia (10%), general fatigue (10%), liver disorder (6%) and thrombocytopenia (6%).
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PMID:Phase II study of oral administration of 5'-deoxy-5-fluorouridine (5'-DFUR) for solid tumors. 624 May 46

Many clinical trials have tested the combination of 5-fluorouracil and recombinant alpha-interferons in metastatic colorectal carcinoma. The efficacy of 5-fluorouracil and lymphoblastoid interferon was evaluated in a phase II study in which 31 patients with advanced colorectal carcinoma were enrolled. 5-Fluorouracil was administered at the dose of 600 mg/sqm bolus weekly and lymphoblastoid interferon was given intramuscularly at 3 million units every two days. All patients were evaluable for toxicity. Thirty patients were available for response: no complete response was recorded, three patients reached a partial response (10%), three a minor response (10%) and 18 progressed (59.4%). Overall median survival was 8 months. No grade IV toxicity was observed: in 2 patients grade III occurred and in 8 patients grade III fever and fatigue attributable to interferon developed. It appears that this combination does not yield better results than 5-fluorouracil alone.
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PMID:Treatment of metastatic colorectal carcinoma with lymphoblastoid interferon and 5-fluorouracil: data of a phase II study. 784 May 14

5-Fluorouracil (5-FU) activity has been improved by the use of leucovorin (LV) or alpha-2a interferon (alpha-IF). We investigated the feasibility and activity of addition of alpha-IF to a 5-FU/LV regimen. A phase I study with 26 patients (14 previously untreated, 12 previously treated) with disseminated cancer was conducted. 15 patients were treated with 5-FU/LV and 11 with 5-FU/LV/alpha-IF. The 5-FU/LV regimen consisted of escalating doses of 5-FU bolus intravenously on days 2 and 3, combined with repeated oral LV on days 1, 2 and 3. Treatment was every 2 weeks. In the 5-FU/LV/alpha-IF schedule, 18 x 10(6) U alpha-IF subcutaneously daily was added on days 1, 2 and 3. The phase I study was followed by a phase II study of 5-FU/LV/alpha-IF at the established 5-FU dose in 29 previously untreated patients with disseminated colorectal cancer. The optimal 5-FU dose in both parts of the phase I study was 750 mg/m2/day. Mucositis, diarrhea and leucopenia were dose limiting. Although alpha-IF added its own toxicity (fever, flu-like symptoms, fatigue), it did not decrease the optimal dose of 5-FU. In the phase II study 28 patients were evaluable for response: three complete responses and 12 partial responses were observed (response rate 54%, 95% confidence interval, 34 to 72%). Pharmacokinetics of oral LV was performed in patients treated with and without alpha-IF: significantly higher serum levels of LV and 5-methyltetrahydrofolate were found after alpha-IF addition. Influence of alpha-IF on gastrointestinal absorption or renal clearance could be excluded. In conclusion, this 5-FU/LV/alpha-IF combination seems active in metastatic colorectal cancer. The pharmacokinetic interaction between alpha-IF and LV may play a role in the activity of this regimen. Controlled studies are necessary to establish the value of addition of alpha-IF to 5-FU/LV regimens.
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PMID:Phase I-II study of the addition of alpha-2a interferon to 5-fluorouracil/leucovorin. Pharmacokinetic interaction of alpha-2a interferon and leucovorin. 839

The activity and toxicity of UFT (Tegafur and Uracil) in a 4:1 molar concentration, plus leucovorin (LV), were evaluated in the treatment of 45 patients with advanced, bidimensionally measurable metastatic colorectal carcinoma. Initially 350 and later 300 mg/m2/day, plus 150 mg LV, as administered in divided doses every 8 h for 28 days. After two courses of treatment, responses were evaluated. The overall response rate was 42.2%, with responses observed in liver (n = 18), lung (n = 6), and bone (n = 1). Five of the 7 patients who received 350 mg/m2 UFT experienced prolonged grade 3 diarrhea, resulting in a dose reduction to 300 mg/m2; 9 patients in the 300-mg/m2 group experienced grade 3 diarrhea, vomiting, abdominal cramping, and fatigue. Minor toxic effects included oral mucositis and rash. The oral regimen of 300 mg/m2/day UFT, plus 150 mg/day LV, administered for 28 days appears to have significant activity against metastatic colorectal carcinoma. The treatment is well tolerated; neutropenia did not occur, and oral mucositis was not significant, even though both are characteristic of intravenous schedules of 5-fluorouracil plus LV. The results of this trial constitutes the basis of phase III clinical trials comparing this oral schedule with intravenous 5-FU and LV to compare clinical efficacy, impact on well-being, and cost. In addition, the current National Surgical Adjuvant Breast and Bowel Project (NSABP) adjuvant colon clinical trial (CO-6) will compare this 28-day schedule of UFT plus oral leucovorin with a weekly regimen of intravenous 5-fluorouracil plus leucovorin in the postoperative adjuvant therapy of Dukes' B and C colon cancer patients.
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PMID:Phase II study of UFT plus leucovorin in colorectal cancer. 897 80

We previously reported results of a Phase II trial of UFT [Taiho Pharmaceutical Ltd., Tokyo, Japan; (BMS-200604) Bristol-Myers Squibb, Princeton, NJ], an oral 4:1 molar concentration of uracil and tegafur, plus oral leucovorin for metastatic colorectal carcinoma (Pazdur et al., J. Clin. Oncol. 12:2296-2300, 1994]. Our results demonstrated that a 28-day schedule of this combination produced a response rate similar to that obtained with conventional intravenous fluorouracil (5-FU)-plus-leucovorin regimens but without the severe or life-threatening neutropenia or oral mucositis that complicates intravenous 5-FU regimens. The current Phase I trial examines the dose-limiting toxic effects and maximum tolerated dose of a 14-consecutive-day schedule of UFT plus oral leucovorin in 14 patients who had histologically proven cancer and had received prior chemotherapy. The daily UFT plus leucovorin dose was divided into three doses administered orally every 8 hours. In this study, the UFT dose was escalated while the leucovorin dose remained at 150 mg/day. Of the 14 patients, 4 were initially treated at the 350-mg/m2/day UFT level for 14 days without any dose-limiting toxic reactions. Subsequently, another 7 patients were treated at the 400-mg/m2/day level; grade 3 diarrhea developed in 3 of these 7 (with severe abdominal cramping in 2 cases and severe nausea and vomiting unresponsive to antiemetics in the third). To better define the starting dose for phase II studies, an additional 3 patients were treated at the 350-mg/m2/day dose level. Of the total 7 patients treated at 350 mg/m2/day, grade 3 toxic events (diarrhea) developed in 2 patients. Grade 1-2 toxic effects noted at this level included fatigue, stomatitis, skin rash, abdominal pain, nausea, and vomiting. Neither partial nor complete responses were observed in this trial. The maximum tolerated dose of this schedule is 350 mg/m2/day UFT plus 150 mg/day oral leucovorin. However, because of this schedule's inferior dose intensity compared with that of the 28-day schedule of UFT plus leucovorin, subsequent development of UFT in the United States has focused on the 28-day regimen.
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PMID:Phase I trial of uracil-tegafur (UFT) plus oral leucovorin: 14-day schedule. 922 Feb 91

The combination of IFN-alpha-2a (IFN-alpha) and IFN-gamma-1b (IFN-gamma) has been found to produce more than additive cytotoxicity with fluorouracil (5-FU) in HT 29 colon cancer cells due to enhanced DNA-directed effects. We therefore studied the combination of IFN-gamma with IFN-alpha, 5-FU, and leucovorin (LV) in a clinical trial. Fifty-three patients received an initial cycle of 5 million units (MU)/m2 IFN-alpha s.c. on days 1-7 with 500 mg/m2 LV and 370 mg/m2 5-FU i.v. on days 2-6. IFN-gamma was then added once tolerable doses of 5-FU and IFN-alpha were established for each patient. IFN-gamma was administered at one of six dose levels between 0.3-4.8 MU/m2 s.c. on days 1-7. This design permitted comparison of the clinical toxicity and pharmacokinetics of 5-FU in two consecutive cycles in an individual treated with the same doses of 5-FU/LV/IFN-alpha in the absence and presence of IFN-gamma. In 43 matched patient cycles, the addition of IFN-gamma did not seem to worsen gastrointestinal toxicity, and skin toxicity tended to be milder. 5-FU clearance was higher in 14 cycles with IFN-gamma compared to the patient's prior cycle with the same doses of 5-FU/LV/IFN-alpha: 798 +/- 309 versus 601 +/- 250 ml/min/m2 (mean +/- SD; P = 0.04). In these 28 cycles, the median 5-FU clearance was significantly lower in 11 cycles that were complicated by more severe diarrhea: 524 versus 798 ml/min/m2 (grade 2 versus 0-1; P = 0. 0032). Overall, 38% and 26% of patients had grade 3-4 diarrhea and mucositis. Dose reductions of IFN-gamma for chronic fatigue, malaise, or anorexia were ultimately required more frequently with >/=2.4 MU/m2 (P = 0.018), and the maximum tolerated dose of IFN-gamma was considered to be 1.2 MU/m2/ day. Objective responses were seen in 41% of 29 measurable colorectal cancer patients. Compared to our previous experience with 5-FU/LV/IFN-alpha, IFN-gamma and IFN-alpha appeared to have opposite effects on 5-FU clearance. These results suggest that any potential benefit of adding IFN-alpha to 5-FU/LV on this schedule may not depend solely on alterations in 5-FU clearance.
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PMID:A pilot study of gamma-1b-interferon in combination with fluorouracil, leucovorin, and alpha-2a-interferon. 981 92

5-Fluorouracil (5-FU) is an effective enhancer of radiation therapy (RT) in head and neck cancers. Due to rapid, predominantly hepatic metabolism by dihydropyrimidine dehydrogenase (DPD) and suggested clinical benefit from prolonged drug exposure, 5-FU is commonly given by continuous infusion. Eniluracil is a novel DPD-inactivator designed to prolong the half-life of 5-FU and provide sustained plasma concentrations of 5-FU with oral dosing. We conducted a Phase I study of the safety and efficacy of eniluracil given with oral 5-FU in patients receiving concurrent RT for recurrent or advanced squamous cell carcinomas of the head and neck. Thirteen patients with recurrent, metastatic, or high-risk (defined as an expected 2-year survival rate of <10%) head and neck cancer were enrolled and treated with concomitant chemoradiotherapy on an every-other-week schedule. Eniluracil at a fixed dose [20 mg twice a day (BID)] was given for 7 consecutive days (days 1-7). 5-FU and RT were given on 5 consecutive days (days 2-6). One patient was treated with once-daily RT (2.0 Gy fractions). The remaining patients received hyperfractionated RT (1.5-Gy fractions BID). The initial dose of 5-FU was 2.5 mg/m2 given BID. Dose escalation in patient cohorts was scheduled at 2.5-mg/m2 increments, with intrapatient dose escalation permitted. Lymphocyte DPD activity and serum 5-FU and uracil concentrations were monitored during two cycles. DPD activity was completely or nearly completely inactivated in all patients. Sustained, presumed therapeutic concentrations of 5-FU were observed at a dose of 5.0 mg/m2 given BID. Cumulative dose-limiting myelosuppression (both neutropenia and thrombocytopenia) was observed during the fourth and fifth cycles following administration of 5.0 mg/m2 5-FU BID. One patient died of neutropenic sepsis during cycle 4. Other late cycle toxicities included diarrhea, fatigue, and mucositis. Grade 3 mucositis was observed in 4 patients, but no grade 4 mucositis or grade 3 or 4 dermatitis was observed. A second patient death occurred during cycle 1 of treatment. No specific cause of death was identified. The study was subsequently discontinued. Cumulative myelosupression was the significant dose-limiting toxicity of oral 5-FU given with the DPD-inactivator eniluracil on an every-other-week schedule. Clinical radiation sensitization was not observed, based on the absence of dose-limiting mucositis and dermatitis. Alternative dosing schedules need to be examined to determine the most appropriate use of eniluracil and 5-FU as radiation enhancers.
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PMID:Phase I study of eniluracil, a dihydropyrimidine dehydrogenase inactivator, and oral 5-fluorouracil with radiation therapy in patients with recurrent or advanced head and neck cancer. 1003 77

A 57 year-old man visited our hospital with general fatigue and a sensation of abdominal fullness. He had lost 10 kg in body weight during the previous 3 months. Between admission and the time the diagnosis of AFP-producing gastric carcinoma with multiple liver metastases was made, his condition deteriorated quickly due to the rapid growth of the liver metastases. Combined chemotherapy consisting of cisplatin and 5-FU was given, and was so effective that the patient recovered well and both serum AFP level and the size of the swollen liver decreased markedly. However, about a month after being discharged, he experienced a relapse and was readmitted. After obtaining informed consent, chemotherapy consisting of methotrexate and 5-FU was started. Though the level of tumor markers and LDH decreased significantly, he died of hepatic failure. We think that this case is worthy of notice because it shows the effectiveness and limitations of chemotherapy in a situation where the condition of a patient is deteriorating quickly due to rapid extension of an AFP-producing gastric carcinoma.
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PMID:[A case study of alpha feto protein (AFP)-producing gastric carcinoma with multiple liver metastases, in which chemotherapy was effective enough to once save a life in rapid decline]. 1083 44

Eighteen patients with non-small cell lung cancer (NSCLC) who had previously received no systemic chemotherapy, were treated on this phase II study with interferon-alfa-2b 8 MU tiw, leucovorin 500 mg/m2 IVPB over 2 hours and 5-Fluorouracil 500 mg/m2 i.v. for 6 weeks followed by a 2-week rest. There were was no rest period for interferon. Median age of patients on this study was 63 years. Fatigue, nausea, and diarrhea were the most common toxicities. There were no grade IV toxicities and no treatment-related deaths. Seven partial responses (39%) with median duration of 4.5 months were seen. An additional patient has had stable disease/minor response for 12+ months. Median survival is 10 months. ALF has activity in NSCLC.
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PMID:Alpha interferon-2b, leucovorin, and 5-fluorouracil (ALF) in non-small cell lung cancer. 1085 42

To evaluate the therapeutic effects and systemic toxicities of a capecitabine-based home therapy regimen in patients with metastatic renal cell carcinoma, 30 patients were enrolled in a phase II clinical trial. Treatment consisted of oral capecitabine combined with subcutaneous recombinant human interferon-alpha 2a, recombinant human interleukin-2 and oral 13-cis-retinoic acid. There were two (7%) complete responses (CRs) and eight (27%) partial remissions (PRs), for an overall objective response rate of 34% (95% CI 17-53%). Except one, all responses are ongoing, with a median duration of 9+ and 8+ months for CRs and PRs, respectively. Additionally, 12 patients (40%) reached stable disease. Eight patients (27%) showed continued disease progression despite treatment. Therapy was well tolerated and was given in the outpatient setting. Capecitabine-related World Health Organization (WHO) grade 2 and 3 toxicities were observed in five and two patients respectively, and were limited to fatigue, nausea/vomiting, diarrhoea, stomatitis, dermatitis and hand-and-foot syndrome. The substitution of capecitabine for 5-FU in the pre-existing biochemotherapy regimen did not result in a reduced therapeutic efficacy and showed significant anti-tumour activity in patients with advanced renal cell carcinoma.
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PMID:Capecitabine in the treatment of metastatic renal cell carcinoma. 1094 96


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