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)

We investigated the reconstitutive potential of haematopoietic progenitor cells collected in autologous whole blood during multicycle dose-intensified chemotherapy. Forty patients with metastatic solid tumours were treated with up to six cycles of cisplatin and escalating doses of ifosfamide every 14 days. Cisplatin was administered in 3% sodium chloride over 3 h, followed by ifosfamide over 24 h and mesna over 36 h. The first cohort of patients received granulocyte colony-stimulating factor (G-CSF) days 4-14. Once dose-limiting toxicity was reached in cohort 1, the study continued with a second cohort of patients, in whom, in addition to G-CSF on days 4-14, 500 ml of G-CSF and chemotherapy-'primed' whole blood was collected on day 15, i.e. on day 1 of treatment cycles two to six, before cisplatin administration. This volume of blood was kept unprocessed at 4 degrees C and reinfused 20-24 h after the completion of ifosfamide. In cohort 1, dose-limiting toxicity (DLT) was reached at ifosfamide 6.0 g m(-2) with two out of six of the patients developing neutropenic fever. Although in cohort 2 no neutropenic fever was encountered, neither the frequency nor the duration of grade 4 neutropenia and thrombocytopenia were reduced. Cumulative asthenia resulted in DLT at 7.0 g m(-2). The median number of CD34+ cells in 500 ml of whole blood after the first cycle (i.e. at start of cycle 2) was 1.15 x 10(6) kg(-1). This number was significantly greater after the second cycle (2.06 x 10(6) kg(-1), P = 0.01) and then gradually decreased after cycles three to six. After storing whole blood, the number of CD34+ cells had not decreased (median + 10%). We conclude that the method of combined bone marrow support by G-CSF and haematopoietic progenitor cells in autologous whole blood collected before each cycle of a 2-weekly regimen of cisplatin-ifosfamide does not result in clinically measurable reduced bone marrow toxicity compared with what can be expected by the use of G-CSF alone.
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PMID:A phase I/II study of multicyclic dose-intensive chemotherapy supported with G-CSF, or G-CSF and haematopoietic progenitor cells in whole blood, in two consecutive cohorts of patients. 964 59

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

Based on the already known in vitro synergy between paclitaxel (taxol), cisplatin and oxazophosphorine cytostatics and the broad spectrum of activity of the above drugs we sought to evaluate the paclitaxel (taxol)-ifosfamide-cisplatin (PIC) combination in the outpatient setting in individuals with a variety of advanced solid tumours. Cohorts of patients were entered into six successive dose levels (DLs) with drug doses ranging as follows: paclitaxel 135-215 mg m(-2) day 1 - (1 h infusion), ifosfamide 4.5-6.0 g m(-2) (total dose) - divided over days 1 and 2, and cisplatin 80-100 mg m(-2) (total) - divided over days 1 and 2. Granulocyte colony-stimulating factor was given from day 5 to 14. Forty-two patients were entered. Eighteen patients had 2-8 cycles of prior chemotherapy with no taxanes or ifosfamide (cisplatin was allowed). The regimen was tolerated with outpatient administration in 36/42 patients. Toxicities included: grade 4 neutropenia for < or = 5 days in 27% of cycles; 5 episodes of febrile neutropenia in three patients at DL-III, -V and -VI. Grade 3/4 thrombocytopenia and cumulative grade 3 anaemia were seen in 7% and 13% of cycles respectively. Three cases of severe grade 3 neuromotor/sensory neuropathy were recorded at DL-II, -III, and -V, all after cycle 3. The maximum tolerated dose was not formally reached at DL-V, but because of progressive anaemia and asthenia/fatigue, it was decided to test a new DL-VI with doses of paclitaxel 200 mg m(-2), ifosfamide 5.0 g m(-2) and cisplatin 100 mg m(-2); this appeared to be tolerable and is recommended for further phase II testing. The response rate was 47.5% (complete response + partial response: 20/42). The PIC regimen appears to be feasible and safe in the outpatient setting. Care should be paid to neurotoxicity. Phase II studies are starting in non-small-cell lung cancer, ovarian cancer and head and neck cancer at DL-VI.
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PMID:Phase I study of dose-escalated paclitaxel, ifosfamide, and cisplatin (PIC) combination chemotherapy in advanced solid tumours. 1064 81

This phase I study was designed to develop a high-dose combination of two cycles of mitoxantrone and cyclophosphamide in patients with solid tumors, as an alternative to single-cycle high-dose regimens that use only alkylating agents. Treatment was delivered with granulocyte colony-stimulating factor (G-CSF), but without stem cell support, in order to avoid potential tumor cell reinfusion. Thirty-one patients with advanced solid tumors received two cycles of high-dose mitoxantrone (20-30 mg/m2) plus high-dose cyclophosphamide (3000-4000 mg/m2). All patients received G-CSF until hematologic recovery. Dose-escalation was performed when less than 50% of cycles per level had dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) achieved was mitoxantrone 25 mg/m2 and cyclophosphamide 4000 mg/m2. Main dose-limiting toxicities (DLTs) were hematological: grade IV neutropenia lasting more than 7 days and thrombopenia below 20 x 10(9)/l requiring more than one platelet transfusion. Non-hematological DLT consisted predominantly of grade III emesis and asthenia. Follow-up after each cycle was performed in an outpatient setting and there were no toxic deaths. In conclusion, the administration of two cycles of high-dose mitoxantrone and cyclophosphamide with G-CSF support is safe and feasible. MTD was mitoxantrone 25 mg/m2 and cyclophosphamide 4000 mg/m2. Evaluation of this regimen is being done in a phase II trial.
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PMID:High-dose mitoxantrone and cyclophosphamide without stem cell support in high-risk and advanced solid tumors: a phase I trial. 1128 78

The purpose of this phase II trial was to evaluate the toxicity of a sequential chemoradiotherapy approach using docetaxel, cisplatin, and 5-fluorouracil (5-FU) (DCF) with granulocyte colony-stimulating factor support in previously untreated patients with locally advanced head and neck cancer (HNC). Secondary endpoints included preliminary assessment of response. Patients with locally advanced HNC, a World Health Organization performance status 0 to 2, and no prior history of chemotherapy or radiotherapy were included. Treatment consisted of docetaxel 80 mg/m2 (1-hour infusion) on day 1, cisplatin 40 mg/m2 (1-hour infusion) on days 2 and 3, and 5-fluorouracil 1,000 mg/m2 (24-hour continuous infusion), on days 1 to 3, repeated every 28 days for a maximum of 4 cycles per patient. All patients received granulocyte colony stimulating factors subcutaneously between days 4 and 9. Radiation therapy (RT) to the primary tumor site and neck lymph nodes was planned within 5 weeks of the last cycle of chemotherapy. The primary tumor site received 60 to 70 Gy. Twenty patients (median age 56 years, range: 40-72 years) received a total of 60 cycles of DCF. The median number of cycles was 3 (range: 1-4 cycles). All patients were evaluable for toxicity and response. The most common acute nonhematologic toxicities from DCF induction chemotherapy included alopecia, mucositis, peripheral sensory neuropathy, onycholysis, and asthenia. Febrile neutropenia developed in two patients and grade IV diarrhea in one patient. There were no treatment-related deaths. The overall response rate (RR) after DCF induction chemotherapy was 90% (95% confidence interval [CI]: 76.8-103.1%). After the completion of RT, the overall RR was 95% with a complete response rate of 73% (95% CI: 49.9-90.1%). Organ preservation was achieved in eight patients with laryngeal cancer and one patient with base of tongue involvement. After a median follow-up of 36 months (range: 5-43 months) the median disease-free and overall survival have not been reached yet. The 1- and 2-year survival rates were 85% and 60%, respectively. Sequential chemoradiotherapy with DCF and growth factor support is feasible and very active, with durable responses in patients with locally advanced head and neck cancer. Further evaluation of this modality is justified in the context of a clinical trial.
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PMID:Sequential chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil in patients with locally advanced head and neck cancer. 1140 90

We studied the safety, activity and peripheral blood progenitor cell mobilizing capability of a dose-dense combination of vinorelbine (VNB) and paclitaxel (PTX) as first-line chemotherapy for patients with metastatic breast cancer (MBC). Forty-three MBC patients were submitted to four cycles of VNB 30 mg/m2 and PTX 175 mg/m2 intravenously, every 2 weeks, as the first induction step of a tandem high-dose chemotherapy program. Granulocyte colony-stimulating factor (G-CSF) 5 microg/kg was administered daily from day +5 to +10 in order to accelerate hematopoietic recovery, or 48h after the last VNB-PTX when a leukapheresis was planned (after the third or fourth cycle). A total of 172 cycles were administered. The mean delivered dose-intensity of VNB and PTX was 14.7 and 86 mg/m2/week, respectively (98% of the planned dose-intensity). The main per-patient toxicities were: peripheral neurotoxicity (G1/2 60%, G3 5%), constipation (G1/2 10%), oral mucositis (G1/2 20%), and asthenia (G1/2 35%). Hematological toxicity was unremarkable, except for anemia with hemoglobin (Hb) values < 10 g/dl (28%), and lymphopenia with lymphocyte counts < 1000/mm3 (28%). Two complete (5.1%) and 24 partial (61.5%) responses were observed in 39 assessable patients, for an overall response rate of 66.6% (95% CI 51.6-80.9). A median of one apheretic procedure (range 1-3) was required to achieve the target number of 6 x 10(6)/kg CD34+ cells. The median number of CD34+ harvested per patient was 15 x 10(6)/kg (range 6.4-36.5). Four cycles of dose dense VNB and PTX showed a favorable toxicity profile, a relevant anti-tumor activity and a high peripheral blood progenitor cell mobilizing activity.
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PMID:Dose-dense vinorelbine and paclitaxel with granulocyte colony-stimulating factor in metastatic breast cancer patients: anti-tumor activity and peripheral blood progenitor cell mobilization capability. 1470 65

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

The purpose of this study was to evaluate the efficacy and tolerance of combined treatment with docetaxel-cisplatin as first-line chemotherapy in patients with metastatic breast cancer (MBC). Consecutive eligible chemonaive patients received docetaxel 75 mg/m(2) on day 1 and cisplatin 75 mg/m(2) on day 2 every 3 weeks for 6 cycles, with prophylactic recombinant human granulocyte colony-stimulating factor (rHuG-CSF) on days 4-11. Thirty-two patients (64%) had received prior adjuvant chemotherapy; these included 16 (32%) who had received anthracyclines. In 50 evaluable patients with a median age (range) of 56 (31-72) years, the overall response rate was 68% (95% CI, 55-81%), with 7 (14%) complete and 27 (54%) partial responses. Stable and progressive disease was observed in 10 (20%), and 6 (12%) patients, respectively. The median duration of response was 10 months, and the median time to progression was 39 weeks. Grade 3/4 hematological toxicity included--neutropenia in 9 patients (18%), anemia in 2 (4%) and thrombocytopenia in 1 (2%). One patient (2%) with febrile neutropenia required hospitalization. Grade 3/4 nonhematological toxicities included nausea/vomiting in 18%, nephrotoxicity in 14%, asthenia (4%), and neurotoxicity (2%). Toxicity was common in older patients (>56 years). There were no treatment-related deaths. A combination of docetaxel-cisplatin with rHuG-CSF support is well tolerated and effective as first-line chemotherapy in MBC.
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PMID:First-line chemotherapy with docetaxel and cisplatin in metastatic breast cancer. 1576 83

We conducted a phase II study to determine the activity and tolerability of weekly paclitaxel, 5-fluorouracil (5-FU) and folinic acid plus granulocyte colony-stimulating factor (G-CSF) support in anthracycline-pre-treated or -resistant metastatic breast cancer patients. The phase II study was designed following the Simon optimal-two stage method. Patients received paclitaxel 80 mg/m, folinic acid 10 mg/m and bolus infusion of 5-FU 300 mg/m every week plus G-CSF on day 3 for 24 consecutive weeks in the absence of disease progression. From May 1998 to May 2000, 51 patients entered the study. Patients received a median relative dose intensity of 97.5% (range 81-100%). No severe toxicities were observed. Seven patients (14%) experienced neutropenia grade 2. Seven patients (14%) experienced grade 2 anemia. Two patients (4%) experienced severe asthenia. Three out of 50 evaluable patients [6%, 95% confidence interval (CI) 2-12.6%] showed a complete response, whereas 23 (46%, 95% CI 32.2-59.8%) had a partial response, with an overall response rate of 52% (95% CI 38.2-65.8%). In addition, eight patients (15.7%) had stable disease. In the 13 patients untreated for metastatic disease, the overall response rate was 92.3% (CI 77.8-100), with one complete response and 11 partial responses (84.6% CI 65-100%). In the whole group, the median time to progression and overall survival were 8 (range 1-18) and 14 months (95% CI 11-17), respectively. Thus, in metastatic breast cancer patients pre-treated with anthracyclines, the weekly administration of paclitaxel, 5-FU and folinic acid with G-CSF support seems to be extremely tolerable and active.
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PMID:Weekly paclitaxel, 5-fluorouracil and folinic acid with granulocyte colony-stimulating factor support in metastatic breast cancer patients: a phase II study. 1652 Jun 64

We conducted a phase II study to determine the activity and tolerability of weekly epirubicin-paclitaxel and granulocyte colony-stimulating factor in breast cancer patients untreated for metastatic disease. The phase II study was designed following the Simon optimal-two stage method. Patients received epirubicin 25 mg/m and paclitaxel 80 mg/m every week, and granulocyte colony-stimulating factor on days 2 and 4 for 24 consecutive weeks in the absence of progression. From 1999 to 2004, 53 patients entered the study; 1093 weekly courses were delivered, with a median number of cycles of 22. Patients received a median relative dose intensity of 94%. No hematological grade 3-4 toxicities were observed. One patient had one episode of grade 3 mucositis and two patients (3.8%) suffered grade 2 asthenia. Eight patients (15.1%) experienced grade 2 neutropenia, grade 2 anemia was registered in seven patients (13.2%). No cardiotoxicity was observed. Ten out of 53 patients (18.9, 95% confidence interval 8.3, 29.4%) showed a complete response, whereas 28 (52.8, 95% confidence interval 39.4, 66.3%) had a partial response, with an overall response rate of 71.7% (95% confidence interval 59.6, 83.8%). In addition, 14 patients (26.4%) had stable disease. Median time to progression was 12 months (95% confidence interval 7, 17). Median response duration was 14 months (range 3-60). The 1-, 3- and 5-year survival rates were 90.1, 68.0 and 56.6%, respectively. In untreated metastatic breast cancer patients, the weekly administration of epirubicin and paclitaxel with granulocyte colony-stimulating factor support seems to be extremely tolerable and active, and deserves further investigation into a phase III trial.
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PMID:Weekly epirubicin and paclitaxel with granulocyte colony-stimulating factor support in previously untreated metastatic breast cancer patients: a phase II study. 1776 97


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