Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Background: Adverse drug reactions (ADRs) are a threat to patients' health and quality of life, and can generate significant expenses. They are generally underreported, with different rates in different health care systems. Methods: We conducted a 6-month survey of all primary admissions to the medical emergency department of a university hospital and assessed the rate, characteristics, avoidability, and marginal costs of ADRs. Results: A total of 7% of all admissions were mainly caused by ADRs. The most frequent were gastrointestinal bleeding (22.3%) and febrile neutropenia (14.4%). Anticancer drugs were involved in 22.7% of the cases, and anticoagulants, analgesics, and non-steroidal anti-inflammatory drugs in 8% each. Physicians had prescribed 70% of these drugs. Patients were predominantly treated in intermediate care units and ordinary wards. The mean cost per case amounted to CHF 3586+/-342, or a total of CHF 821204 over the 6-month-period (1 CHF=0.56 US$=0.87 Euro). A total of 67% were considered definitely imputable to drug effects and 32% were retrospectively regarded as avoidable. Conclusions: Interventions aimed at reducing the incidence of ADRs should be directed towards both patient education and physician training. This could save hospitals admissions and money, and could be used as an indicator of prescription quality.
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PMID:Rate, type, and cost of adverse drug reactions in emergency department admissions. 1155 31

The present trial was designed to determine the efficacy of the combination of gemcitabine/doxorubicin/paclitaxel (GAT) delivered every other week as first-line therapy in patients with metastatic breast cancer. From February 1998 to September 1999, 41 patients were included in this trial. Doses delivered were doxorubicin 30 mg/m2 on day 1 and paclitaxel 135 mg/m2 plus gemcitabine 2500 mg/m2 both given on day 2, every 14 days. Doses were selected from a previous phase I trial conducted at our institution. Eligibility criteria for the phase II trial included histologically confirmed metastatic breast cancer with bidimensionally measurable lesions; no prior therapy for metastatic disease; adjuvant or neoadjuvant chemotherapy was allowed if given more than 1 year before and cumulative doses of doxorubicin or epirubicin were less than 200 mg/m2 or 360 mg/m2, respectively; Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less; and adequate hematological, hepatic, and renal function. Prophylactic use of granulocyte colony-simulating factor (G-CSF) was allowed if patients were not fully recovered (absolute neutrophil count greater than 1500/microL) from chemotherapy administration before the next dose. Left ventricular ejection fraction was determined initially, at the end of the study, and every 6 months thereafter. The patients' median age was 55 years (range, 33-68 years), and their median ECOG performance status was 0 (range, 0-1). Twenty-eight patients had received adjuvant therapy, 17 with epirubicin (none with doxorubicin). Metastases were present in the bone (19 patients), lung (19 patients), liver (11 patients), and soft tissues (18 patients). Twenty patients had one metastatic site and 21 had two or more sites. Efficacy was assessed on an intent-to-treat basis. A total of 216 cycles of GAT were given. Twenty-two percent of the courses were delayed or given at reduced doses mostly due to neutropenia or thrombocytopenia. G-CSF was required in 58% of the cycles. Grade 3/4 neutropenia was the main toxicity and appeared in 17 patients, one of whom had an episode of febrile neutropenia. Nonhematological toxicities consisted mainly of neurotoxicity and myalgias. A drop of 10%-20% in the left ventricular ejection fraction was detected in two patients and another patient had a decrease greater than 20%, although none developed symptoms of heart failure. Overall response rate was 80.4% (95% confidence interval: 68.3-92.5), with 15 patients (36.6%) achieving a complete response. Median survival time was 27 months and median time to progression was 15 months. The GAT combination is feasible and very active in patients with metastatic breast cancer, with an encouraging response rate including a high rate of complete responses. No congestive heart failure was documented and other toxicities were mild, with the exception of neutropenia.
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PMID:Phase II trial of gemcitabine/doxorubicin/paclitaxel administered every other week in patients with metastatic breast cancer. 1189 47

The aim of this study was to investigate the benefit of weekly epirubicin in the treatment of metastatic hormone-resistant prostate cancer. One hundred and forty-eight patients with metastatic hormone-resistant prostate cancer received weekly 30-min intravenous infusions of epirubicin 30 mg m(2) of body surface area. The primary end-point was palliative response, defined as a reduction in pain intensity and an improvement in performance status. The secondary end-points were the duration of the palliative response, quality of life and survival. Fifty-seven (44%) of the 131 evaluable patients met the primary criterion of palliative response after six treatment cycles and 73 (56%) after 12 cycles; the median duration of the response was 9 months (range 1-11). The median global quality of life improved in 52% of the patients after six cycles and in 68% after 12 cycles. The 12- and 18-month survival rates were respectively 56 and 31%, with a median survival of 13+ months (range 1-36). The treatment was well tolerated: grade 3 neutropenia was observed in 8% of the patients, grade 3 anaemia in 7%, and grade 3 thrombocytopenia in 3%. None of the patients developed grade 4 toxicity or congestive heart failure. Weekly epirubicin chemotherapy can lead to a rapid and lasting palliative result in patients with metastatic HRPC, and have a positive effect on the quality of life and survival.
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PMID:Weekly epirubicin in patients with hormone-resistant prostate cancer. 1223 53

Based on the recommended phase II doses for doxorubicin (60 mg/m2) and docetaxel (60 mg/m2) and the National Surgical Adjuvant Breast and Bowel Project's (NSABP) experience with doxorubicin and cyclophosphamide (cyclophosphamide 600 mg/m2), we conducted a phase II trial at 18 institutions using doxorubicin/docetaxel/cyclophosphamide (ATC) given every 21 days, in preparation for a major adjuvant breast cancer study (NSABP B-30), in which ATC would be used. Eligibility requirements included measurable stage IIIB/IV breast cancer, performance status 0-2, normal left ventricular ejection fraction, and no prior chemotherapy for metastatic disease (nontaxane adjuvant chemotherapy was allowed if completed > 12 months before entry and if the cumulative dose of doxorubicin was =240 mg/m2). Eighty-nine patients were entered who ranged in age from 30-78 years (38.2% < 50 years; 61.8% =50 years). A total of 33.7% of patients had stage IIIB disease, and 66.3% had stage IV disease. Among the stage IV patients, 20.3% had received prior adjuvant chemotherapy. Dexamethasone premedication (8 mg p.o. b.i.d. for 3 days) and prophylactic ciprofloxacin (500 mg p.o. b.i.d. days 5-15) were used. Colony-stimulating growth factors were reserved for secondary prophylaxis after prolonged or febrile neutropenia (FN) or documented severe infection in a prior cycle. After a cumulative dose of doxorubicin 480 mg/m2, patients could continue with docetaxel/cyclophosphamide alone. Eighty-nine patients and 577 courses were evaluable for toxicity. Median time on study as of May 2002 was 36.5 months (range, 28-47 months). Febrile neutropenia occurred in 34 patients (38%); 8 developed FN in the absence of prior prophylactic growth factor support; 26 developed FN despite prior growth factor support (for one patient this information was unavailable). There were no septic deaths. One patient died from pulmonary embolism. Other grade 3/4 adverse events included: nausea (9%), vomiting (7%), stomatitis (6%), diarrhea (4%), arthralgia/myalgia (3%), and neurotoxicity (1%). Clinical congestive heart failure was seen in 3 patients (3.4%). Seventy-seven patients were evaluable for best response within 6 cycles of therapy. Thirteen patients (16.9%) had a complete response, 43 (55.8%) had a partial response, for an overall response rate of 72.7%. The median response duration was 23.8 months (95% CI, 16.2-37.8 months), and the median time to progression or death was 23.5 months (95% CI, 16.3-38.7 months). The median survival time was 35.6 months (95% CI, 26.6-39.4 months). The administration of ATC with primary ciprofloxacin and secondary colony-stimulating factor prophylaxis is feasible and active. Its value in the adjuvant setting is currently under investigation.
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PMID:Phase II trial of doxorubicin/docetaxel/cyclophosphamide for locally advanced and metastatic breast cancer: results from NSABP trial BP-58. 1253 63

The therapeutic efficacy of weekly coadministration of paclitaxel (TXL) and pirarubicin (THP) on docetaxel (TXT)- and epirubicin-resistant recurrent breast cancer, adverse reactions caused by this therapy, and the possibility of ambulatory treatment using it were evaluated. The present study was conducted in 11 patients with recurrent breast cancer with pretreatment with CEF and TXT. The site of recurrence was the lung in 9 patients, lymphnodes in 2, bones in 1, liver in 1 and local foci in 1. One cycle consisted of 20 mg/m2 of THP followed by 80 mg/m2 of TXL 4 h later, repeated three times every other week. Three to six cycles were conducted in each patient. An anti-emetic drug was administered before administration of THP as short premedication. Dexamethasone (16 mg; i.v.) and d-chlorpheniramine maleate (12 mg; p.o.) were administered 1 h before administration of TXL and ranitidine (100 mg; i.v.) was administered 30 min before administration of TXL. Ubidecarenone (30 mg/day; p.o.) was administered for 3 days. The response rate was 27.3% with a rating of PR in 3 patients, NC in 6, and PD in 2. Adverse reactions observed included transient facial hot flushes, alopecia grade 1 or milder grade 1 symptoms, and peripheral nerve damage. No adverse reactions such as myocardial disorders or congestive heart failure were noted. Grade 3 and grade 2 neutropenia occurred in 1 and 6 patients, respectively, and 4 patients were admitted for treatment of this. In conclusion, the short premedication was useful, and this was thought to make it possible to conduct ambulatory treatment with TXL + THP in some patients. The response rate of 27.3%, however, was not satisfactory. It will be necessary to clarify the characteristics of this therapy by administering it to a wider spectrum of patients.
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PMID:[Weekly administration of paclitaxel and pirarubicine for recurrent breast cancer]. 1255 13

Preclinical data suggest that the combination of inhibitors of topoisomerases I and II may be synergistic when administered together. The optimal sequence of such combinations is uncertain, but initial administration of a topoisomerase I inhibitor upregulates topoisomerase II. Several combinations of these inhibitors have been evaluated, but have not clearly demonstrated synergy. Thus, we have started a phase I study of the combination of irinotecan (CPT-11, Camptosar) and epirubicin (Ellence). Typical eligibility criteria for phase I studies were employed. Patients with a history of congestive heart failure, > 240 mg/m2 of prior doxorubicin, or > 10% weight loss in the prior 4 weeks were excluded. Irinotecan and epirubicin were administered on days 1 and 8, every 28 days. Initially, patients were treated with irinotecan at 100 mg/m2 and epirubicin at 40 mg/m2 (dose level 1). After substantial toxicity at this level, the doses to be evaluated were changed to irinotecan: 50-->75-->100 mg/m2, and epirubicin: 20-->25-->30 mg/m2. Dose-limiting toxicities were noted in 2/4 patients (2 neutropenic fever, 1 thrombocytopenia) on dose level 1; 0/3 on dose level 1A; 1/8 (neutropenia) on dose level 2A; and 1/3 (neutropenia) on dose level 3A. This is the first combination of irinotecan and epirubicin to be evaluated in humans. The toxicity, primarily myelosuppression, noted to date has exceeded the expected toxicity for the doses of the irinotecan and epirubicin alone, suggesting the possibility of a synergistic interaction of the agents on this schedule, at least in the bone marrow. Other toxicities were acceptable and non-dose-limiting. Accrual of patients continues, at level 3A (irinotecan at 75 mg/m2, epirubicin at 25 mg/m2).
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PMID:Combined inhibition of topoisomerases: a phase I. Study of irinotecan and epirubicin. 1280 Jun 7

This phase II trial studied the efficacy and toxicity of docetaxel-epirubicin, supported by granulocyte colony-stimulating factor, as first-line chemotherapy in metastatic breast cancer. Patients received epirubicin (60 mg/m2) followed 1 hour later by docetaxel (80 mg/m2) every 3 weeks for a maximum of 8 cycles or until disease progression. Prophylactic granulocyte colony-stimulating factor (5 micrograms/kg) was administered daily for 5 days. Sixty-nine patients were evaluable for efficacy and toxicity. Objective responses occurred in 45 patients (65%; 95% confidence interval: 53-76%), with 11 (16%) complete responses and 34 (49%) partial responses. Responses were observed at all metastatic sites. The median response duration was 8 months (range 4-68), median time to progression was 10 months (range 4-68) and median overall survival was 24 months (range 7-68): neutropenia was dose limiting (46% grade 3-4 toxicity). The left ventricular ejection, fraction measured in 50 patients, fell below normal in 14 patients (28%), 8 patients had grade 1 and 6 grade 2 cardiotoxicity, but none developed congestive cardiac failure. The docetaxel-epirubicin regimen is extremely effective in poor prognosis breast cancer patients with visceral metastases, with significant overall and complete responses, followed by prolonged survival in responders. Although myelosuppression remains the major toxicity, prophylactic GCSF administration was associated with a small percentage of neutropenic fever.
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PMID:Docetaxel and epirubicin supported by granulocyte colony-stimulating factor first-line in advanced breast cancer. 1292 35

In patients with advanced breast cancer, treatment with paclitaxel and doxorubicin has been shown to produce impressive overall response rates (up to 94%) and to prolong overall survival significantly over a combination of fluorouracil (5-FU), doxorubicin, and cyclophosphamide (Cytoxan, Neosar) in one prospective phase III clinical study. These results have been challenged, however, by other data demonstrating no survival advantage for taxane-based therapies. In addition, the combination of paclitaxel and doxorubicin has repeatedly been shown to be complicated by the development of treatment-related congestive heart failure, when cumulative doxorubicin doses exceed 300-360 mg/m2. Consequently, attempts have been made to increase the complete remission rate and overall survival resulting from first-line treatment of metastatic breast cancer without compromising patient safety. Gemcitabine (Gemzar)--a relatively effective, well-tolerated and partially non-cross-resistant antitumor compound with limited toxicity--represents an attractive alternative to paclitaxel/anthracycline combinations. Initial studies of combination therapy with gemcitabine and paclitaxel have produced an average response rate of 52%, with time to progression ranging between 7.0 and 14.5 months. Three-drug regimens containing gemcitabine, an anthracycline, and paclitaxel have been tested in phase II studies and have produced impressive response rates of 82.9% with gemcitabine, doxorubicin, and paclitaxel and 92% with gemcitabine, epirubicin (Ellence), and paclitaxel (GET). The Central European Cooperative Oncology Group has evaluated the GET regimen vs a regimen containing 5-FU, epirubicin, and cyclophosphamide (FEC) in a randomized, prospective phase III study. Interim toxicity analysis showed that the GET regimen was well tolerated but produced more grade 4 neutropenia (64% vs 42%, P = .084) and significantly more grade 4 thrombocytopenia (12% vs 0%; P < .001) than FEC. Anaphylactic/allergic reactions, peripheral polyneuropathy, nausea, and cardiotoxicity constituted rare events and did not exceed grade 1 or 2 in severity. Although final data from this phase III trial are not yet available, preliminary analysis suggests the GET regimen represents an attractive option for patients with advanced breast cancer.
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PMID:Gemcitabine, anthracycline, and taxane combinations for advanced breast cancer. 1476 4

This phase II trial studied the efficacy and toxicity of full dose paclitaxel plus vinorelbine, as salvage chemotherapy in patients with metastatic breast cancer resistant to anthracyclines. Patients received vinorelbine (30 mg/m2) followed 1 hour later by full dose paclitaxel (175 mg/m2) every 3 weeks for a maximum of 8 cycles or until disease progression. Because of the heavy pretreatment of the patients, prophylactic granulocyte-colony stimulating factor (5 microg/kg) was administered daily for 5-10 days. To minimize potentially cumulative neurotoxicity due to both agents, amifostine was given prior to chemotherapy. Thirty-four patients: 8 with tumors primary resistant and 26 with tumors recurring within 3-6 months after anthracycline treatment, were evaluable for efficacy and toxicity. Objective responses occurred in 11 patients [32%; 95% confidence interval (CI): 16.3-47.7%), all partial responses. Responses were observed in lung and liver. The median response duration was 4 months (range 3-7), median time to progression was 5 months (range 3-9) and median overall survival was 8 months (range 4-24). Neutropenia was dose limiting (35% grade 3-4 toxicity). The left ventricular ejection fraction, measured and followed in 18 patients, fell less than 20% below baseline level in 9 patients (50%), but only one patient developed congestive cardiac failure. The paclitaxel-vinorelbine regimen was moderately tolerated and moderately effective in poor prognosis breast cancer patients with visceral metastases and tumors resistant to anthracyclines. The combination at these doses and schedules should be considered in the design of regimens for advanced breast cancer.
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PMID:Full dose paclitaxel plus vinorelbine as salvage chemotherapy in anthracycline-resistant advanced breast cancer: a phase II study. 1499 89

We evaluated the efficacy and toxicity of trastuzumab plus gemcitabine in patients with HER2-positive metastatic breast cancer (MBC). Sixty-four patients were enrolled, the majority of whom (95%) had been treated with an anthracycline and a taxane before study enrollment. Eligible women were treated with gemcitabine (1200 mg/m(2) weekly for 2 weeks with the third week off on a 21-day cycle) plus weekly doses of trastuzumab (4-mg/kg loading dose; 2 mg/kg thereafter) until disease progression. The median patient age was 55 years, and the median number of previously administered (including adjuvant) chemotherapy regimens was 3. Twenty-two patients were scored as 2+ for HER2 expression by immunohistochemistry; 39 patients scored 3+. Three patients were assessed as HER2-negative on central pathology review and were ineligible for evaluation. Fifty-nine of the 61 patients remained evaluable for response. The objective response rates were 38% in the intent-to-treat population (23 of 61) and 44% among the 39 patients with HER2 3+ expression. The median response duration was 5.8 months, median overall survival was 14.7 months, and median time to disease progression was 5.8 months. Trastuzumab plus gemcitabine was well tolerated. No cases of clinical congestive heart failure occurred. Grade 3/4 toxicities included asthenia in 4 patients, fever in 4, neutropenia in 18, dyspnea in 6, abdominal or back pain in 3, and edema and nausea in 1 patient each. The combination of trastuzumab plus gemcitabine appears to be well tolerated and effective for patients with HER2-positive MBC previously treated with chemotherapy.
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PMID:Phase II study of trastuzumab plus gemcitabine in chemotherapy-pretreated patients with metastatic breast cancer. 1524 19


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