Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004093 (asthenia)
 2,650 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutropenia is the dose-limiting toxicity of docetaxel in children. This Phase I trial was designed to determine the maximum tolerated dose, the dose-limiting toxicities, and the incidence and severity of other toxicities of docetaxel with filgrastim (G-CSF) support in children with refractory solid tumors. Docetaxel was administered as an i.v. infusion for 1 h every 21 days with a starting dose of 150 mg/m2 and an escalation to 185 mg/m2 and 235 mg/m2 in subsequent patient cohorts. G-CSF (5 microg/kg/day) was administered s.c., starting 48 h after docetaxel and continuing until the post-nadir neutrophil count reached 10,000/microl. Seventeen patients received 27 courses of docetaxel with G-CSF support. Generalized erythematous desquamating skin rash and myalgias were dose-limiting at 235 mg/m2. Localized and generalized rashes were seen at all of the three dose levels. Neutropenia (median nadir, 95/1microl) occurred at all of the dose levels but was brief in duration and not dose-limiting. Thrombocytopenia was minimal (median platelet count nadir, 139,000/microl), and the severity of neutropenia and thrombocytopenia did not seem to be related to the docetaxel dose. Other docetaxel-related toxicities included hemorrhage (associated with mucositis), sepsis, hypersensitivity reaction, transient elevation of liver enzymes, stomatitis, back pain, asthenia, and neuropathy. One minor response was observed in a patient with colon cancer. The maximum tolerated dose of docetaxel with G-CSF support in children is 185 mg/m2, which is 50% higher than the maximum tolerated dose of docetaxel alone in children and 85 % higher than the recommended adult dose.
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PMID:Phase I trial of docetaxel with filgrastim support in pediatric patients with refractory solid tumors: a collaborative Pediatric Oncology Branch, National Cancer Institute and Children's Cancer Group trial. 1021 6

A prospective phase II study was conducted to determine the response, toxicity and survival rate of lung cancer patients treated with combination paclitaxel and carboplatin in stage IIIB and IV NSCLC. Eligible patients required measurable and/or evaluable diseases; performance status (ECOG) 0-2; no previous chemotherapy; adequate hepatic, renal and bone marrow function. Paclitaxel was administered at a dose of 200 mg/m2, 3 h infusion, followed by carboplatin at an AUC of 6. Treatment was repeated every 3 weeks for six courses. G-CSF 5 microgram/kg was subcutaneously injected during subsequent courses if there was grade 3-4 leucopenia or granulocytopenia in the previous course. From April 1996 through July 1997, 53 patients were enrolled; all are assessable for toxicity and response. The median age was 56 years (range, 20-77 years). Sixty four percent were male, 64% had adenocarcinoma and 62% had stage IV disease. Two hundred and seventy two courses were administered; 36 patients (68%) completed all six cycles. Two patients achieved a complete response (4%) and 27 patients achieved a partial response (51%), for an overall response rate of 55%. Sixteen patients had stable disease (30%) and 8 patients had progressive disease (15%). The median progression free survival time for all patients, stage IIIB and stage IV patients was 28 weeks (range, 18-37 weeks), 31 weeks (range 21-41 weeks) and 22 weeks (range 16-29 weeks), respectively. The median survival time and 1 year survival rate for all patients was 55 weeks (range, 51-59 weeks) and 55%, respectively. Stage IIIB patients had better median survival time and 1-year survival rate than stage IV patients (75 vs. 46 weeks, P = 0.007; 80% vs. 42%, P = 0.003). Grade 3 and 4 granulocytopenia, anemia and thrombocytopenia were observed in 25, 3, and 1%, respectively, of the 272 courses administered. G-CSF was required in 28% of the 272 courses. There were four episodes of febrile neutropenia (1.5%), three episodes of angina pectoris (1%) and one episode of anaphylaxis (0.4%). Other common toxicities, generally mild, included myalgia, arthralgia, peripheral neuropathy and asthenia. Most toxicities showed cumulative effect. Paclitaxel plus carboplatin is a moderately active regimen in advanced NSCLC. Toxicities of this regimen are well tolerated.
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PMID:Phase II study of paclitaxel and carboplatin for advanced non-small-cell lung cancer. 1059 28

The aim of this study was to evaluate the feasibility of a high-dose intensity and high-dose density multicycle epirubicin and cyclophosphamide regimen with peripheral blood stem cells (PBSC) and haematopoietic growth factor (G-CSF) support in advanced breast cancer patients. From August 1994 to September 1999, 56 breast cancer patients (8 stage IIIB and 48 stage IV) received 205 courses of cyclophosphamide 3 g x m(-2) and epirubicin 100 mg x m(-2) every 14 days. G-CSF 5 microg x kg(-1) x day(-1) was administered from day 3 to neutrophil recovery. 4 courses were planned. PBSC were collected after course 1, and reinfused after courses 3 and 4, with > or = 2 x 10(6) CD34+ PBSC x kg(-1) required for each reinfusion. 48 patients (86%) received all 4 planned courses. Early withdrawal was consecutive to infectious complications (n = 4), severe asthenia (n = 3), haemorrhagic cystitis (n = 1). A median number of 10.8 x 10(6) CD34+ PBSC x kg(-1) (range, 3-80) was harvested with 1 or 2 apheresis in 48 patients (94%). Median relative dose intensity was 91.3% (range, 72-102%). Grade 4 neutrophil toxicity was observed in 100% of patients. Febrile neutropenia was observed in 40% of courses (median duration 2 days). Red blood cells and platelets had to be transfused in 54% and 27% of courses, respectively. There were no toxic deaths. Objective response rate was 69% in stage IV patients (31/45 evaluable pts), with a 16% complete response rate. Their median progression-free and overall survivals were 22.5 and 37 months, respectively. This epirubicine-containing high-dose regimen appeared feasible, albeit with high toxicity. Time-related progression parameters exceed commonly reported ones. Controlled studies of upfront sequential high-dose chemotherapy are still needed to evaluate its real benefit.
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PMID:High-dose sequential epirubicin and cyclophosphamide with peripheral blood stem cell support for advanced breast cancer: results of a phase II study. 1172 Apr 55

To evaluate the efficacy and toxicity of weekly docetaxel (D) as II line treatment in non-small cell lung cancer (NSCLC), in November 1999, we started a phase II study on advanced (stages IIIB-IV) NSCLC patients pre-treated with at least one platinum-based chemotherapy regimen with or without radiotherapy. The schedule consisted of D 40 mg/m(2), weekly for 6 weeks, followed by a rest period of 2 weeks, for three cycles or until progression. Eligibility criteria were: histopathologic diagnosis of NSCLC; age <or=75 years; evaluable or measurable progressive lesions; PS (ECOG) 0-2; adequate haematology and biochemistry parameters; no serious concurrent diseases; no symptomatic brain lesions; and informed consent. The end points were assessment of overall response rate, toxicity and quality of life (QoL). Patients were re-evaluated at the end of every cycle. An interim analysis of 18 patients (16 M) was performed. Weekly courses were 132; 16 of 18 patients were evaluable for response and 17 of 18 for toxicity. Two of the 16 patients (12.5%) had a partial response (95% CI: 10.5-14.7%). Haematological toxicity was very mild: grade 1-2 neutropenia occurred in four patients, grade 3 neutropenia in two patients; grade 1-2 anaemia in four patients; and grade 1-2 thrombocytopenia in two patients. Non-haematological toxicity was also very mild, with the exclusion of asthenia (grade 1-2 in ten patients and grade 3 in five patients) and alopecia (grade 1-2 in seven patients and grade 3 in eight patients). No cases of grade 4 toxicity were observed. No QoL evaluations were reported in this interim analysis. In conclusion, these preliminary data confirm that weekly D results in tolerable toxicity in pre-treated NSCLC. Myelo-suppression, the dose-limiting toxicity of every 3 week schedules, is not a clinically relevant problem when D is administered weekly. G-CSF was used only sporadically in four patients, and no febrile neutropenia was reported. Patients were pre-treated with dexamethasone and no allergic reactions were seen. Although the therapeutic activity appears to be comparable to that of every 3 week schedules, more data are necessary before definite conclusions can be drawn. Accrual of patients is still ongoing.
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PMID:Weekly docetaxel as II line therapy in non-small cell lung cancer: an interim analysis of a phase II study. 1174

This phase II trial evaluated the efficacy and toxicity of vinorelbine 25 mg/m2 plus docetaxel 60 mg2/m administered on day 1, every 2 weeks with granulocyte colony-stimulating factor support (G-CSF, 5 microg/kg/day, days 3-7) as primary prophylaxis in patients with histologically confirmed metastatic breast cancer (MBC) and previously treated with anthracyclines in the adjuvant or in the first-line setting. A total of 48 patients received 352 cycles (median 8, range 2-10). All patients were included in the efficacy and safety evaluation on an intent-to-treat analysis. Eight patients (17%) showed a complete response and 14 patients (29%) showed a partial response. Overall response rate was 46% [95% confidence interval (CI) 33-60]. The median duration of response was 10.0 months. With a median follow-up of 18.0 months, the median time to progression was 11.9 months and the median overall survival was 27.1 months. The most frequently reported grade 3/4 hematological toxicity was neutropenia (19% of patients, 4% of cycles). Febrile neutropenia was reported in six patients (13%) and 7 cycles (2%), but no toxic deaths were reported. The most common grade 3/4 non-hematological toxicity was asthenia (17% of patients, 6% of cycles) and nail toxicity (15% of patients, 3% of cycles). In conclusion, biweekly docetaxel plus vinorelbine with G-CSF support is active and well tolerated as chemotherapy for patients with MBC resistant to anthracyclines. G-CSF support is recommended for lowering the incidence and severity of neutropenia and febrile neutropenia.
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PMID:Biweekly docetaxel and vinorelbine with granulocyte colony-stimulating factor support for patients with anthracycline-resistant metastatic breast cancer. 1561 8

Docetaxel is an effective treatment approved in five key cancers, but its effectiveness in clinical practice can be compromised by sub-optimal side-effect management. The aim of this review was to investigate the extent of the published work on specific docetaxel-related side effects and to provide, where possible, evidence-based recommendations for their prevention and management. PubMed and the American Society of Clinical Oncology (ASCO) databases were systematically searched for articles published in English over the past 5 and 2 years, respectively, and pertaining to six side effects identified as being common to the majority of docetaxel regimens and indications of particular relevance to the oncology nurse. The Cochrane library was also searched. A total of 103 citations were identified, 14 of which discussed strategies for the prevention or management of febrile neutropenia (n=6), hypersensitivity reactions (3), fluid retention (1) and nail changes (4). No articles were identified that related to asthenia or neuropathy. Based on the literature review, evidence/guidelines-based advice for the use of G-CSF in febrile neutropenia is provided. The evidence base with respect to the other side effects does not permit the formulation of recommendations. It is the experience of the authors, however, that the severity of symptoms experienced by patients is generally mild and the side effects are for the most part easily managed with prophylactic and supportive care measures. It is therefore important to share and build on experiences, through research and discussion, to maximise the healthcare professional's ability to offer the best standard of care to patients.
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PMID:Docetaxel-related side effects and their management. 1850 74

Docetaxel is an effective treatment approved in five key cancers, but its effectiveness in clinical practice can be compromised by sub-optimal side-effect management. The aim of this review was to investigate the extent of the published work on specific docetaxel-related side effects and to provide, where possible, evidence-based recommendations for their prevention and management. PubMed and the American Society of Clinical Oncology (ASCO) databases were systematically searched for articles published in English over the past 5 years and 2 years, respectively, and pertaining to six side effects identified as being common to the majority of docetaxel regimens and indications and of particular relevance to the oncology nurse. The Cochrane library was also searched. A total of 103 citations were identified, 14 of which discussed strategies for the prevention or management of febrile neutropenia (n=6), hypersensitivity reactions (3), fluid retention (1) and nail changes (4). No articles were identified that related to asthenia or neuropathy. Based on the literature review, evidence/guidelines-based advice for the use of G-CSF in febrile neutropenia is provided. The evidence base with respect to the other side effects does not permit the formulation of recommendations. It is the experience of the authors, however, that the severity of symptoms experienced by patients is generally mild and the side effects are for the most part easily managed with prophylactic and supportive care measures. It is, therefore, important to share and build on experiences, through research and discussion, to maximise the healthcare professional's ability to offer the best standard of care to patients.
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PMID:Docetaxel-related side effects and their management. 1920 49