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)

Between February 1990 and December 1991 high-dose epirubicin (Epi)(120 mg/m2) plus cyclophosphamide (CTX)(600 mg/m2) were given every 3 weeks to 52 patients with locally advanced and metastatic breast cancer. 26 patients with locally advanced disease received four courses of this regimen before and after local treatments. 26 patients had metastatic disease: they received eight courses unless progression or unacceptable toxicity occurred. Responses were seen in 37/48 (77%) evaluable patients including 14 complete responses (CR), 23 partial responses (PR), nine stable disease, two progressive disease. Among the 25 evaluable patients with locally advanced disease, 9 had a CR and 11 a > 80% decrease in tumour volume. 6 patients (24%) had a pathologically confirmed complete response. 18 patients (72%) had a tumour reduction to 0-2 cm. The 3-year disease-free survival was 60%. Of the 23 evaluable patients with metastatic disease, 5 obtained a CR and 10 a PR, yielding an overall response rate of 65%. Myelosuppression was substantial with a grade 3-4 leucopenia in 76% of the patients even if neutropenic fever occurred in only 7% of the courses. A clinical congestive heart failure occurred in 1 patient following a total Epi dose of 960 mg/m2 and a bilateral quadrantectomy and radiotherapy. We conclude that (1) high-dose Epi + CTX is a very active regimen, in particular for the patients with locally advanced breast cancer; (2) breast conservation after this regimen in some of these patients may be considered; (3) neutropenia is the dose-limiting toxicity. Currently, a phase II study using the same combination given every 2 weeks together with r-methuG-CSF is ongoing.
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PMID:Phase II trial of high-dose epirubicin and cyclophosphamide in advanced breast cancer. 799 14

An intensive chemotherapy regimen (EVDAC), including high-dose epirubicin, vincristine, and dexamethasone followed by cyclophosphamide and high-dose cytarabine, was administered to 54 untreated adults with intermediate or high-grade non-Hodgkin's lymphomas (NHL). The median age was 59, 61% were Ann Arbor Stage IV, 57% had "B" symptoms, 50% had serum lactate dehydrogenase greater than 250 U/L, and 48% had masses greater than 7 cm (33% > 10 cm) in diameter. Seventy-six percent of patients attained complete or probable complete remissions. The Kaplan-Meier actuarial failure-free survival at 7 years is 50%, and 59% (32 of 54) of all patients started on therapy remain alive and in first remission at a median of 62+ (range, 49+ to 76+) months from completion of therapy. Nearly all patients developed severe neutropenia. Febrile episodes requiring hospitalization during neutropenia occurred after 56% of courses of epirubicin, vincristine, and dexamethasone and after 9% of courses of cyclophosphamide and cytarabine; 80% of patients were hospitalized at least once. Platelet count nadirs of less than 20,000/microL occurred after only 1 of 146 evaluable courses of epirubicin and after none of the cyclophosphamide/cytarabine courses. Although 8 patients had decreases of at least 0.12 in their left ventricular ejection fractions (5 to below normal levels), none have developed clinically evident congestive heart failure. Clinically significant mucositis occurred after only 8% of courses of high-dose epirubicin. Three deaths from infections and one from hyperkalemia with cardiac arrest occurred during therapy. These results confirm that high remission and sustained, failure-free survival rates can be achieved in patients with aggressive NHL, using high-dose anthracycline-containing chemotherapy regimens. Epirubicin appears to have an advantage over doxorubicin at high doses because of decreased toxicity at a therapeutically equivalent dose. These phase II study results need to be validated in a randomized phase III trial, and growth factors should be used to attempt to reduce the neutropenia-associated complications.
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PMID:Chemotherapy of intermediate- and high-grade non-Hodgkin's lymphomas with an intensive epirubicin-containing regimen. 826 Jun 95

The taxanes paclitaxel and docetaxel are undergoing extensive evaluation in women with breast cancer in the United States and in Europe. Their dose-limiting toxicity is neutropenia. Paclitaxel also causes peripheral neuropathy, while docetaxel can cause unpredictable and severe skin toxicity, as well as edema and effusions due to a capillary leak syndrome. Due to threshold pharmacodynamics and nonlinear pharmacokinetics, tolerability of paclitaxel is schedule dependent. Single-agent paclitaxel was very active in multiple phase II trials in patients with different numbers and types of prior chemotherapy and disease extent (20% to 60% complete plus partial responses). Effective doses ranged from 135 to 250 mg/m2. Activity was observed with all infusion schedules (1, 3, and 24 hours) and in women with anthracycline-resistant tumors (25% to 38%). The use of a 96-hour infusion schedule was very active in anthracycline-refractory patients (48%) and in women who failed short infusion taxanes. The drug is undergoing extensive evaluation in combination with doxorubicin, cyclophosphamide, cisplatin, and antimetabolites. Very promising efficacy was observed for paclitaxel by 3-hour infusion plus bolus doxorubicin (approximately 40% complete responses and 50% partial responses). The combination also caused a high incidence of clinically reversible congestive heart failure(14% to 18%). Docetaxel also has very good efficacy in breast cancer, with approximately 70% major responses in untreated patients and more than 50% in anthracycline-resistant tumors. There is no evidence that efficacy and tolerability are schedule dependent as is the case for paclitaxel. At recommended doses (100 or 75 mg/m2 by 1-hour infusion every 3 weeks), docetaxel causes a fluid retention syndrome that may affect quality of life. Its common onset after multiple cycles may limit the use of docetaxel for palliation in metastatic breast cancer. These results clearly indicate that the taxanes will become a standard component of initial chemotherapy for women with breast cancer. The definition of their actual role still requires an answer to the unresolved questions of their optimal dose and combination with other anticancer agents. Most importantly, the drugs should be prospectively evaluated in a randomized study using comparable doses and schedules to assess which of the two has the better therapeutic index in breast cancer.
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PMID:The role of taxanes in the treatment of breast cancer. 861 49

The activity of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been documented in untreated and previously treated metastatic breast cancer, including both patients with anthracycline-resistant disease and those with extensive pretreatment. Such activity has prompted investigations of the optimal doses and schedules of paclitaxel/doxorubicin combinations. With one exception, paclitaxel has been administered as either a 24- or a 3-hour infusion, while the administration times for doxorubicin vary from bolus injection to 72-hour infusion. Results of these completed phase I and II trials are reviewed. Also reported are two European trials that have achieved promising results. In Milan, a phase I/II trial has shown a preliminary response rate exceeding 90% in 32 chemotherapy-naive patients treated with an alternating schedule of paclitaxel given over 3 hours and intravenous bolus doxorubicin. At doses of paclitaxel 200 mg/m2 and doxorubicin 60 mg/m2, the dose-limiting toxicities were neutropenia, oral mucositis, myalgias, and peripheral neuropathy. Congestive heart failure occurred in six patients. A phase I/II study of a 30-minute doxorubicin infusion preceding a 3-hour paclitaxel infusion every 3 weeks in minimally pretreated patients also is reported. Of 29 patients evaluable for response, 17 have achieved partial responses and seven complete responses, for an overall response rate of 83% (95% confidence interval, 79% to 99%). Toxicities observed were grades 3 to 4 neutropenia and moderate paresthesias, nausea/vomiting, alopecia, myalgia, and mucositis. Cardiotoxicity also occurred, as 15 patients had a significant decrease in left ventricular ejection fraction measured by isotope cardiography. Six of these developed congestive heart failure. This effect has been observed only in studies using short infusions of both drugs, and it is now being investigated whether lowering the peak doxorubicin concentration will preclude it.
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PMID:Paclitaxel and doxorubicin, a highly active combination in the treatment of metastatic breast cancer. 862 30

The activity of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) against untreated and previously treated metastatic breast cancer (documented in anthracycline-resistant disease and in extensively pretreated patients as well) has prompted investigations of the optimal doses and schedules of paclitaxel/doxorubicin combinations. With one exception, paclitaxel has been administered in either a 24- or a 3-hour infusion, while the administration times for doxorubicin vary from bolus injection to a 72-hour infusion. Results of these completed phase I and II trials are reviewed. Also reported are two ongoing European trials that have achieved promising preliminary results. In Milan, a phase I trial has achieved a preliminary response rate exceeding 90% in 30 chemotherapy-naive patients treated with an alternating schedule of paclitaxel over 3 hours and intravenous bolus doxorubicin. At doses of paclitaxel 200 mg/m2 and doxorubicin 60 mg/m2, the dose-limiting toxicity is leukopenia and mucositis. Furthermore, congestive heart failure has occurred in six patients. We are conducting a phase I/II study in minimally pretreated patients, with a 30-minute doxorubicin infusion preceding a 3-hour paclitaxel infusion every 3 weeks. Of 24 patients evaluable for response, five have achieved partial responses and three complete responses. (Another five partial and two complete responses need confirmation.) Of the two dose levels now given, all responses occurred at the higher paclitaxel/doxorubicin level, 175 and 60 mg/m2, respectively. Despite grades 3 and 4 neutropenia in 31% and 60% of courses, respectively, only six patients have been hospitalized for febrile neutropenia. Of concern, the left ventricular ejection fraction has decreased to below normal in six patients and two have developed symptomatic congestive heart failure. Whether lowering the peak doxorubicin concentration will preclude this effect, which has been observed only in the studies using short infusions of both drugs, is under investigation.
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PMID:Treatment of metastatic breast cancer with paclitaxel and doxorubicin. 864 64

Intravenous immune globulin (IVIg) is advocated as a safe treatment for immune-mediated neurologic disease. We reviewed the medical records of 88 patients who were given IVIg for a neurologic illness. Major complications in four patients (4.5%) included congestive heart failure in a patient with polymyositis, hypotension after a recent myocardial infarction, deep venous thrombosis in a bed-bound patient, and acute renal failure with diabetic nephropathy. Other adverse effects included vasomotor symptoms 26, headache 23, rash 5, leukopenia 4, fever 3, neutropenia 1, proteinuria (1.9 g/day) 1, viral syndrome 1, dyspnea 1, and pruritus 1. Fifty-two patients (59%) had some adverse effect of IVIg infusion, most commonly vasomotor symptoms, headaches, fever, or shortness of breath in 40 (45%), which improved with reduced infusion rate or symptomatic medications. Five (6%) had asymptomatic laboratory abnormalities and seven (8%) had other minor adverse effects. Adverse effects led to discontinuation of therapy in 16% and permanent termination of therapy in 10% of patients. There was no mortality or long-term morbidity. Although adverse effects were frequent, serious complications were rare except in patients with heart disease, renal insufficiency, and bed-bound state.
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PMID:Complications of intravenous immune globulin treatment in neurologic disease. 930 72

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is active against advanced breast cancer and anthracycline-resistant breast cancer. We assessed the efficacy and toxicity of doxorubicin followed by a 3-hour infusion of paclitaxel in women with advanced breast cancer. Participants could have received at most one prior adjuvant chemotherapy regimen, but no previous exposure to anthracyclines or taxanes was permitted. The patients were treated every 3 weeks with doxorubicin (50 or 60 mg/m2) followed 30 minutes later by paclitaxel (155, 175, or 200 mg/m2). After reaching the maximum cumulative doxorubicin dose, treatment could be continued with paclitaxel alone. Thirty women were included, of whom 29 were evaluable for response. The overall response rate was 83% (95% confidence interval, 64% to 94%), with 24% of patients attaining complete remission. Median response duration for complete responders was 8+ months (range, 4 to 13 months) and median time to progression was 9 months (range, 2 to 18 months). Main toxicities were neutropenia, paresthesia, nausea/vomiting, alopecia, myalgia, and cardiotoxicity. In 15 patients (50%), the left ventricular ejection fraction decreased to below normal levels; six patients (20%) developed congestive heart failure. In conclusion, the combination of doxorubicin and paclitaxel is highly active; dose-limiting toxicities are neutropenia, neuropathy, and cumulative cardiotoxicity.
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PMID:Doxorubicin and paclitaxel, a highly active combination in the treatment of metastatic breast cancer. 889 95

We performed a dose escalation study to evaluate the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given over 3 hours plus bolus epirubicin 90 mg/m2. The starting dose of paclitaxel, 135 mg/m2, was escalated by 20-mg/m2 increments in cohorts of three to six patients. Courses were repeated every 3 weeks. Filgrastim (5 micrograms/kg/d) was administered to shorten the duration of grade 4 neutropenia lasting longer than 72 hours. Twenty-nine patients have been treated, 86% of whom had failed adjuvant chemotherapy (with anthracyclines in 14 cases). One hundred forty-eight courses have been administered, and the paclitaxel dose has been escalated to 225 mg/m2 without reaching the maximum tolerated dose. The most frequent dose-related toxicity has been grade 4 neutropenia, which occurred in 59% of courses. The median duration of grade 4 neutropenia was 4 days, which was shortened with filgrastim only in patients treated with paclitaxel 225 mg/m2. Eleven episodes of febrile neutropenia (7% of courses) have been observed. Nonhematologic toxicities were mild or moderate: grade 1 or 2 peripheral neuropathy was reported by 41% and 10% of patients, respectively. The cardiac toxicities of this regimen were surprisingly low: median left ventricular ejection fraction was 57% at study entry and 56% after six courses. Only two patients showed a decrease of left ventricular ejection fraction below 50% after six courses, and no signs of anthracycline-induced congestive heart failure were noted. The activity of this novel combination is encouraging: the overall response rate is 80%, with 16% complete responses. We have demonstrated that the combination of epirubicin plus paclitaxel given over 3 hours is feasible with acceptable toxicities, does not appear to be associated with clinically relevant cardiotoxicity, and is active in a population of patients who have failed adjuvant chemotherapy.
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PMID:A dose-finding study of epirubicin in combination with paclitaxel in the treatment of advanced breast cancer. 889 96

Thirty-two patients with advanced breast cancer have been treated with epirubicin 90 mg/m2, immediately followed by paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) infused over 3 hours, every 21 days. The starting paclitaxel dose was 135 mg/m2, increased in subsequent triplets of patients until the maximum tolerated dose was reached at 200 mg/m2. One hundred seventy-six courses have been administered; dose-related grade 4 neutropenia was observed in 66% of the courses, with 12 episodes of febrile neutropenia. Two patients showed a decline of left ventricular ejection fraction below 50% after six courses, but no signs of congestive heart failure have been reported. The response rate is 76% (95% confidence interval, 56% to 90%), with 14% complete remissions. This level of activity is encouraging considering that 84% of the patients had failed adjuvant chemotherapy (with anthracyclines in 14 cases), and 19 had progressive disease following hormone therapy for metastasis. In another study, the toxicity and activity of a salvage regimen consisting of paclitaxel 135 mg/m2 over 3 hours plus vinorelbine 25 mg/m2 in an intravenous bolus on day 1 were evaluated; vinorelbine was given again on day 8 (in 14 patients) or on day 3 (in 20 patients), and the courses were repeated every 3 weeks. Thirty-four previously treated patients with advanced breast cancer entered the study; 20 had received one prior line of chemotherapy, II had two lines, and three patients had three lines. Thirty-two patients had been exposed to anthracyclines. Grade 4 neutropenia was observed in 64% of the courses, with 13 episodes of febrile neutropenia; four episodes of grade 3 mucositis have been reported with vinorelbine days 1 and 3. A delay in the administration of chemotherapy was necessary in 17% of the courses with vinorelbine days 1 and 8 and 16% of the courses with vinorelbine days 1 and 3; moreover, the vinorelbine dose was reduced or the drug omitted on day 8 in 86% of the courses and on day 3 in 16% of the course. An objective response was achieved in 43% of the patients. In conclusion, the combination of paclitaxel plus vinorelbine is an active salvage regimen and can be administered at greater dose intensity with the day 1 and 3 schedule.
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PMID:Paclitaxel combinations as front-line and salvage chemotherapy regimens in advanced breast cancer. 899 97

This phase I dose-finding study examined the effects of the combination of doxorubicin and docetaxel (Taxotere) in 42 women with metastatic breast cancer. The combination was studied at six different dosing levels. The maximum tolerated doses were defined as doxorubicin, 50 mg/m2, and docetaxel, 85 mg/m2, with sepsis as the dose-limiting toxicity. Activity was observed at all dose levels, especially at the highest dose levels (50/60, 50/75, 50/85, and 60/60 mg/m2), with a response rate of 81% (95%; confidence interval, 62.5% to 92.5%) in patients treated at these dose levels. The response rate in patients with visceral disease was 74%, and 82% in patients with liver metastasis. Adjuvant chemotherapy with or without anthracyclines did not affect the response rate. The recommended doses were doxorubicin, 50 mg/m2, and docetaxel, 75 mg/m2, or 60 mg/m2 of both drugs, administered on day 1 every 3 weeks, without granulocyte-colony stimulating factor (G-CSF, filgrastim [Neupogen]) support. Neutropenia was the only grade 3 or 4 adverse event. There were no cases of congestive heart failure, a significant decrease in left-ventricular ejection fraction, or interruption of treatment because of fluid retention.
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PMID:Docetaxel in combination with doxorubicin: a phase I dose-finding study. 921 22


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