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 combination chemotherapy (PT treatment) with cisplatin and tetrahydropyranyl-adriamycin (THP-ADM) was performed in 17 patients with head and neck squamous cell carcinoma. Chemotherapy treatment began with an intravenous dose of 50 mg/body cisplatin and an intravenous dose of 20 mg/body THP-ADM. Administration of THP-adriamycin was performed on the first day only, while cisplatin treatment was repeated once a day until the third day. Five of the 17 cases achieved complete response (29.4%) and seven achieved partial response. Response rate was 70.6%. Toxicity was mild and controlled with symptomatic treatment. Leukopenia was observed in 71.4% thrombocytopenia 14.3% (due to myelosuppression), appetite loss 38.1%, general fatigue 28.6% and nausea and vomiting 23.8%. No electrocardiographic abnormality was noted.
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PMID:Combined chemotherapy and radiation therapy in head and neck cancer. 879 Jul 67

A phase II trial of the new anthrapyrazole piroxantrone was carried out by the Southwest Oncology Group in patients with advanced metastatic or recurrent endometrial cancer. A two-stage statistical design targeted accrual of 20 eligible patients. The starting dose of piroxantrone was 150 mg/m2 in patients without prior radiation therapy (RT) and 120 mg/m2 in patients with prior RT. There were 15 eligible patients, six of whom had received prior hormonal therapy while nine patients had not received prior hormonal therapy. Eight patients had received prior RT while seven patients had not received any prior RT. One to seven cycles of piroxantrone were administered. Dose escalation was feasible in four patients. No grade 5 toxicity was experienced by any patients. Most of the grade 4 (granulocytopenia in one) and grade 3 (leukopenia in three, granulocytopenia in three, anemia in two and thrombocytopenia in one) toxicity was related to myelosuppression. Grade 3 non-hematologic toxicities were nausea, fatigue and SGOT elevation. There was one partial response for a response rate of 7% (95% CI 0.2-32%) and median survival was 11 months (95% CI 3-13 months). The study was prematurely terminated due to lack of patient accrual.
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PMID:A phase II trial of piroxantrone in endometrial cancer: Southwest Oncology Group study 8918. 886 19

This is the first report of successful treatment of recurrent retinoblastoma with vitreous seeding by a combination of ranimustine (MCNU) and carboplatin. The patient was diagnosed with bilateral retinoblastoma at 3 years of age. Although he received photocoagulation and radiotherapy for the left eye after enucleation of the right eye, a recurrent tumor associated with vitreous seeding developed 6 years later. The child underwent chemotherapy with cyclophosphamide and nimustine hydrochloride (ACNU), and a transient decrease of tumor cells in the vitreous was seen. We then changed the chemotherapy regimen to MCNU (70 mg/m2/ day for 1 day) and carboplatin (400 mg/m2/day for 2 days). After five courses of this chemotherapy, the tumor in the vitreous completely disappeared. No recurrence has been observed for > 4 years. Side effects, including myelosuppression, general fatigue, and vomiting, were observed during the course of chemotherapy, but they were ameliorated with supportive therapy. Neither nephro- nor ototoxicity was observed. The patient has useful vision. These results warrant further study of this novel drug combination in patients with recurrent, or even primary, retinoblastoma.
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PMID:Successful treatment with ranimustine and carboplatin for recurrent intraocular retinoblastoma with vitreous seeding. 893 71

A combination of platinum and a taxane is regarded by many as the optimum treatment for advanced epithelial ovarian carcinoma. A recent meta-analysis has suggested that the addition of an anthracycline to platinum-based chemotherapy is associated with a significant survival advantage. We are therefore conducting an ongoing phase I/II study combining drugs from these three classes. We report here the first phase using carboplatin at an area under the concentration-time curve of 7, doxorubicin 50 mg/m2, and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 175 mg/m2 over 3 hours. The treatment was given on a 3-weekly cycle and granulocyte colony-stimulating factor was given if the nadir neutrophil count fell below 0.5 x 10(9)/L and was continued until recovery. Toxicity was assessed according to the Common Toxicity Criteria. All patients were required to have advanced ovarian cancer (stage IC to IV) but be ineligible for standard chemotherapy trials or to have advanced gynecologic malignancy, such as mixed mullerian tumor, fallopian tube carcinoma, coelomic carcinoma, or primary peritoneal carcinoma. To date, seven patients have been treated, and all were of performance status 0 to 2, 18 to 70 years old, with a life expectancy of > or = 3 months. Hematologic toxicity was significant, with all patients having grade 3/4 thrombocytopenia and six of seven grade 3/4 leukopenia. There was, however, only one grade 3/4 infection. Three patients have experienced fatigue, which in two cases was severe, and one patient had grade 3/4 stomatitis. Dose reduction was due to myelosuppression and was required in five patients. Five patients were evaluable for response, all of whom have obtained complete or partial response. There has been no clinical evidence of cardiotoxicity, but four patients had grade 1/2 cardiotoxicity as measured by left ventricular ejection fraction. We conclude that this combination is active and has acceptable but significant toxicity. It is only suitable for very fit patients, and we are currently assessing ways of reducing toxicity.
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PMID:Taxane/platinum/anthracycline combination therapy in advanced epithelial ovarian cancer. 904 34

Twenty-nine patients with persistent, recurrent and/or metastatic squamous cell carcinoma of the head and neck were treated daily for five days at three-week intervals with topotecan 1.5 mg/m2. Four patients received prior chemotherapy, 23 prior surgery and 29 prior radiation therapy. Of the 29 eligible patients, 8 patients were not evaluable for response and were assumed to be non-responders. Of the remaining 21 evaluable patients, there were zero responses (0%, 95% confidence interval [0,.12]). The most common toxicities were myelosuppression, dyspnea and malaise/fatigue/lethargy. Topotecan has limited activity in advanced head and neck cancer with this dose and schedule.
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PMID:Evaluation of topotecan in patients with recurrent for metastatic squamous cell carcinoma of the head and neck. A phase II Southwest Oncology Group study. 915 77

High-dose chemotherapy is increasingly accepted as a treatment approach in a number of tumour types. However, there are controversies surrounding its efficacy and there is a need to consider its safety. In view of this, much effort has been directed towards the provision of adequate supportive care strategies to prevent toxicities and to ameliorate myelosuppression. Severe anaemia and its associated symptoms, for example, fatigue can have a debilitating effect on a patient's quality of life and often necessitates red blood cell transfusions. Erythropoietin, a glycoprotein hormone which stimulates red blood cell production, has been established for the treatment of anaemia in patients with chronic renal insufficiency. It is currently approved in most countries for treating anaemia associated with cancer, and its role is emerging especially in patients undergoing high-dose chemotherapy. This paper gives an overview of the studies conducted to date with epoetin alfa (recombinant human erythropoietin) in patients receiving allogeneic and autologous bone marrow transplants or peripheral blood stem cells in conjunction with high-dose chemotherapy. In addition, there are some novel clinical applications for epoetin alfa: for example, in delayed anaemia, as a supportive strategy prior to high-dose chemotherapy and as a synergistic enhancer of blood progenitor cell mobilisation in combination with granulocyte-colony-stimulating factor (G-CSF).
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PMID:Haematological toxicities associated with dose-intensive chemotherapy, the role for and use of recombinant growth factors. 934 59

2-Chlorodeoxyadenosine (2-CdA) is a purine nucleoside analogue with therapeutic activity in low-grade lymphoproliferative disorders. In addition, 2-CdA has a potent myelosuppressive effect, and it has been shown to be toxic to malignant myeloid cells both in vitro and in vivo. In this pilot study we treated nine patients who had advanced myelofibrosis with myeloid metaplasia (MMM) and progressive hepatomegaly or symptomatic thrombocytosis after therapeutic splenectomy. 2-CdA was administered at 0.05-0.1 mg/kg/d for 7 d for one to five treatment cycles. A reduction in liver size associated with marked improvement in fatigue and control of thrombocytosis and leucocytosis was achieved in seven of the nine patients (78% response rate). In four of the seven responding patients the reduction in liver size was durable (4-28 months) and was associated with a decrease in serum alkaline phosphatase levels. However, no patient had improvement in anaemia, and two of the seven initially responding patients have since died of acute leukaemia or progressive disease. Improvement in bone marrow fibrosis was noted in two of five available post-treatment marrow examinations. Toxicity was mainly myelosuppression, which was severe in two patients. 2-CdA may be considered a palliative therapeutic agent after splenectomy in noncytopenic patients with MMM who have progressive hepatomegaly or extreme thrombocytosis.
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PMID:2-Chlorodeoxyadenosine treatment after splenectomy in patients who have myelofibrosis with myeloid metaplasia. 969 87

GI1147211 is a 7-substituted 10,11-ethylenedioxy-20(S)-camptothecin analogue that inhibits the nuclear enzyme topoisomerase I. In this Phase I and pharmacological study, 24 patients with advanced solid malignancies received a total of 72 courses of GI147211 as a 30-min infusion daily for 5 consecutive days, at doses ranging from 0.3 to 1.75 mg/m2/day. Severe neutropenia precluded dose escalation above 1.5 mg/m2/day in minimally pretreated patients, and both severe neutropenia and thrombocytopenia were dose limiting in heavily pretreated patients at doses above 1.0 mg/m2/day. These doses are, therefore, recommended for subsequent Phase II evaluations of GI147211 in patients with comparable prior therapy. Nonhematological toxicities, including nausea, vomiting, fatigue, and anorexia, were mild to moderate. The disposition of GI147211 in blood was described by a linear three-compartment model, with renal elimination accounting for only 11% of drug distribution. No relationship was observed between the pharmacological exposure to GI147211 and effects on neutrophils; however, patients who developed dose-limiting myelosuppression did experience greater exposure to both the lactone and total forms of the drug. The hydrolysis kinetics of GI147211 revealed not only a shift of the drug to the inactive carboxylate form in human serum albumin but also stabilization of the lactone in erythrocytes, perhaps accounting for the observed lactone:total area under the concentration-time curve ratio of 0.27. These results indicate that GI147211 exhibits predictable toxicities and that further studies are warranted to determine the distinct role of this compound among currently available camptothecin analogues.
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PMID:Phase I and pharmacokinetic study of GI147211, a water-soluble camptothecin analogue, administered for five consecutive days every three weeks. 953 26

Prolonged exposure to topotecan (TPT) in in vitro experiments and in vivo studies in animals yielded the highest antitumor efficacy. An oral bioavailability of TPT of 32-44% enables convenient prolonged administration. Because of unpredictable diarrhea in the third week of the twice daily (b.i.d.) 21-day schedule of p.o. administered TPT and the finding of optimal down-regulation of topoisomerase I level after 10-14 days in mononuclear peripheral blood cells, a shorter period of administration (10 days) was chosen for Phase I and pharmacological studies of oral administration of TPT. Adult patients with malignant solid tumors that were refractory to standard forms of chemotherapy were entered. Two dose schedules were studied: once daily (o.d.) and b.i.d. administration for 10 days every 3 weeks. TPT o.d. for 10 days was studied at dose levels 1.0, 1.4, and 1.6 mg/m2/day, and dose levels were 0.5, 0.6, 0.7, and 0.8 mg/m2 with the 10-day b.i.d. schedule. Pharmacokinetics were performed on days 1 and 8 of the first course using a validated high-performance liquid chromatographic assay and noncompartmental pharmacokinetic methods. Nineteen patients were entered in the 10-day o.d. schedule, with a total of 48 courses given. Dose-limiting toxicity (DLT) was reached at 1.6 mg/m2/day and consisted of common toxicity criteria (CTC) grade IV thrombocytopenia and CTC grade III diarrhea. The maximum tolerated dose was 1.4 mg/m2/day. In the 10-day b.i.d. administration of TPT, a total of 64 courses were studied in 20 patients. DLT was reached at a dose of 0.8 mg/m2 b.i.d. and consisted of CTC grade IV myelosuppression and CTC grade IV diarrhea. The maximum tolerated dose was 0.7 mg/m2 b.i.d. Nonhematological toxicities with both schedules included mild nausea and vomiting, fatigue, and anorexia. Pharmacokinetics revealed a substantial variation of the area under the plasma concentration-time curve of TPT lactone in both schedules. Significant correlations were observed between the myelotoxicity parameters and the area under the plasma concentration-time curve at day 1 of TPT lactone o.d. and b.i.d. The DLT of 10 daily administrations of oral topotecan every 3 weeks consisted of a combination of myelosuppression and diarrhea for both schedules studied. The recommended doses for Phase II studies are 1.4 mg/m2/day for 10 days for the o.d. administration and 0.7 mg/m2 for the b.i.d. schedule.
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PMID:Oral topotecan given once or twice daily for ten days: a phase I pharmacology study in adult patients with solid tumors. 960 72

An early phase II clinical study of S-1 in patients with advanced or recurrent breast cancer was undertaken by a cooperative study group (Breast Cancer Working Group) of 14 institutes in Japan. S-1 was administered twice daily at 75 or 50 mg (dose FT)/body for 28 consecutive days with 14 days rest (one course). Twenty-eight patients were enrolled, 27 were eligible for the study, and 25 were evaluable for efficacy. Four complete responses and seven partial responses were obtained, and the response rate was 40.7% (11/27) [ninety percent confidence interval for this response was 26.7-56.4%]. The major adverse reactions observed were myelosuppression represented by leukopenia 44.4% (12/27), neutropenia 40.7% (11/27), RBC decreased 37.0% (10/27), hemoglobin decreased 29.6% (8/27), anorexia 55.6% (15/27), nausea/vomiting 48.1% (13/27), and fatigue 33.3% (13/27). The results suggested that the efficacy and safety of S-1 were effective against advanced or recurrent breast cancer. The objective of study judged should be investigated in a late phase II clinical study.
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PMID:[An early phase II clinical study of S-1 in patients with breast cancer. S-1 Cooperative Study Group (Breast Cancer Working Group)]. 964 19


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