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

Taxol, an antineoplastic agent isolated from the Pacific yew, has been demonstrated in three phase 2 clinical trials to have major activity (30 percent overall response rate) in patients with ovarian cancer refractory to cisplatin. The major toxicities associated with the agent are neutropenia (dose-limiting), hypersensitivity reactions, peripheral sensory neuropathy, and cardiac arrhythmias. A recently reported phase 1 trial of the combination of cisplatin and taxol has defined acceptable doses for the two-drug combination to be tested against cisplatin and cyclophosphamide as frontline therapy of advanced ovarian cancer. Taxol has also been examined for intraperitoneal administration in patients with ovarian cancer, with a major pharmacokinetic advantage for peritoneal cavity exposure being demonstrated. Unfortunately, any future development of taxol as an antineoplastic agent in the management of ovarian cancer will be dependent on the finding of an alternative source of the drug, as the current method of obtaining taxol from the bark of the Pacific yew provides insufficient quantities for large-scale clinical use.
 ...
PMID:Taxol: an important new drug in the management of epithelial ovarian cancer. 168 43

Pilot studies were conducted to evaluate the toxicity and efficacy of two relatively marrow-sparing chemotherapy regimens in the treatment of advanced or progressive epidemic Kaposi's sarcoma. Chemotherapy regimens consisted of bleomycin (10 mg/m2), vincristine (1.4 mg/m2, 2 mg maximum) and Adriamycin (doxorubicin) at either 10 mg/m2 (Group I) or 20 mg/m2 (Group II). The therapy was given intravenously, every 2 weeks, until intolerable toxicity or maximum antitumor response. Thirty-three patients were treated. Although the patient populations were similar regarding pretreatment prognostic factors, the patients were not assigned randomly to these two treatment regimens. Major responses (complete or partial remission) were attained in 79% of the cases. The treatment-related toxicities consisted of mild to moderate nausea, hair loss, and peripheral sensory neuropathy. Bone marrow suppression consisted primarily of neutropenia (less than 1000/mm3) which occurred in a third of the patients. Variables significantly associated with shorter survival included hemoglobin (less than 10 g/dl), low Karnofsky performance status (less than 70%), and weight loss. Opportunistic infections occurred in the majority of cases during administration of chemotherapy, and were most likely related to severe cell-mediated immune dysfunction and low CD4-positive lymphocyte counts.
 ...
PMID:Advanced acquired immune deficiency syndrome-related Kaposi's sarcoma. Results of pilot studies using combination chemotherapy. 168 9

In a Phase I trial SR 2508 was administered by rapid intravenous infusion to 102 patients receiving radiation therapy. The dose-limiting toxicity was peripheral sensory neuropathy (PN) which was related to the cumulative dose administered. The highest single daily dose, 3.7 g/m2, was tolerated without toxicity. The lowest cumulative toxic dose was 21.6 g/m2, and the highest non-toxic dose was 40.8 g/m2. Grade 1 neuropathies were mild and self-limited; grade 2 neuropathies were long-lasting and debilitating. In a retrospective analysis, the risk of developing neurotoxicity was related to the cumulative drug exposure calculated by the area-under-the-curve (AUC) of plasma concentration versus time. There was an increased incidence of neuropathy in patients with a cumulative AUC of greater than or equal to 36 mM-hr. At a total dose of 34 g/m2 over 6 weeks, the incidence of Grade 1 neuropathy was approximately 30%; no grade 2 neuropathy occurred at this dose and schedule. Additional toxicities observed included nausea and vomiting (6%), skin rash (4%), and transient arthralgias (3%). One patient had transient abnormalities in liver function tests of unknown etiology. (In a more recent Phase II trial neutropenia has been observed which may be related to SR2508). Approximately three times more SR 2508 is tolerable compared to misonidazole, and it appears that severe neuropathy can be avoided by monitoring individual patient pharmacokinetic parameters. Evaluation of the efficacy of this hypoxic cell sensitizer is in progress.
 ...
PMID:Final report of the phase I trial of the hypoxic cell radiosensitizer SR 2508 (etanidazole) Radiation Therapy Oncology Group 83-03. 215 20

In an attempt to circumvent clinical multidrug resistance, we conducted a Phase II trial of cyclosporin plus combination chemotherapy in patients with relapsed or refractory non-Hodgkin's lymphoma. Thirteen patients, all of whom had been previously treated with a doxorubicin-containing regimen, received doxorubicin 50 mg/m2 intravenous continuous infusion (IVCI) over 96 h (days 1-4), vincristine 2 mg i.v. (day 1), and etoposide 75 mg/m2 i.v. daily for 4 days (days 1-4). Four days prior to chemotherapy, patients received a loading dose of cyclosporin (0.88 mg/kg i.v. over 2 h), followed by a maintenance dose (1.8 mg/kg per day IVCI for 9 days). Cyclosporin dose escalation was permitted, conventionally defined therapeutic levels of cyclosporin were achieved; this drug was well tolerated at these doses. The study was closed due to a poor response rate; only one patient achieved a complete remission of 33 weeks' duration. Grade 3 and 4 toxicities included gastrointestinal haemorrhage (one patient), sensory neuropathy (two patients), stomatitis (two patients), and transaminase elevation (one patient). Asymptomatic grade 1-2 toxicities (elevated creatinine and transaminase levels) occurred in 33% of patients. There were no treatment associated deaths. Prolonged neutropenia and thrombocytopenia were the primary haematological toxicities. Although the addition of cyclosporin at this dose and schedule did not improve response rates in this patient group, future trials using higher doses of cyclosporin with combination chemotherapy may warrant further investigation.
 ...
PMID:Cyclosporin plus doxorubicin, vincristine and etoposide in the treatment of refractory non-Hodgkin's lymphoma: a phase II study. 858 55

Eighteen patients with metastatic non-small cell lung cancer were treated with a combination of intravenous vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Medicament, Paris, France) 25 mg/m2 on days 1 and 8 and intravenous paclitaxel 175 mg/m2 on day 2 every 3 weeks. All patients were given granulocyte colony-stimulating factor 5 micrograms/kg/d subcutaneously on days 3 through 7 and 9 through 17 or until the absolute neutrophil count reached 10 x 10(9)/L or higher. One patient was enrolled in this study too recently to be assessed. The mean age of the remaining 17 patients was 59 years (age range, 33 to 75 years); all but one patient had refractory disease, mostly to cisplatin-containing regimens. Four patients were ineligible (two because of poor performance status and two because of previous exposure to vinblastine). Three partial responses were observed, with durations of 46, 64, and 140+ days. Four patients had stable disease and four had progressive disease. The most common side effect was neutropenia (five grade 4 and one grade 3); two patients died of leukopenic sepsis in the first cycle. Peripheral neuropathy was also common (four grade 1 and one grade 2 sensory neuropathy). Other toxic effects were anemia and nausea and vomiting. The median survival was 153 days in all patients and 179 days in eligible patients. The preliminary results in this ongoing study of combination vinorelbine and paclitaxel as second-line therapy for metastatic non-small cell lung cancer are promising, and using this regimen as first-line therapy is warranted.
 ...
PMID:Pilot study of vinorelbine (navelbine) and paclitaxel in patients with refractory non-small cell lung cancer. 861 Feb 31

A phase I/II study was carried out to determine the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in combination with a fixed dose of carboplatin (area under the concentration-time curve = 6 by Calvert method) given on an every-3-week schedule to patients with non-small cell lung cancer (NSCLC). Cohorts of patients were entered at increasing dose levels of paclitaxel: six at dose level I (paclitaxel 150 mg/m2), six at dose level 2 (paclitaxel 175 mg/m2), 11 at dose level 3 (paclitaxel 200 mg/ m2), 21 at dose level 4 (paclitaxel 225 mg/m2), and five at dose level 5 (paclitaxel 250 mg/m2). The patients comprised 31 men and 18 women with a median age of 62 years (age range, 46 to 81 years) and a median Southwest Oncology Group performance status of I (range, 0 to 2). Twenty-three patients had unresectable stage III NSCLC and 26 had stage IV NSCLC. Fortynine patients and 176 treatment courses are evaluable for toxicity. Grade 4 neutropenia or grade 3 arthralgias/ myalgias or sensory neuropathy were the most significant toxicities of therapy. In addition, two patients (dose levels 2 and 3) experienced acute chest pain, flushing, and hypotension, and had electrocardiogram changes during the paclitaxel infusion; one had mild creatine phosphokidnase MB elevation. Both recovered uneventfully, were not re-treated with paclitaxel, and account for two of only four hospitalizations for toxicity management in this trial. At this time, 42 patients with objectively measurable disease are evaluable for responses: two complete responses and 24 partial responses (62% objective response rate) have been observed. These data imply that the maximum tolerated dose of paclitaxel is 250 mg/m2 with dose-limiting toxicity consisting primarily of grade 3 osteo/arthralgias-myalgias or cumulative sensory neuropathy; paclitaxel at a dose of 225 mg/m2 given by 3-hour infusion combined with carboplatin at a calculated target area under the concentration-time curve of 6 is a well-tolerated outpatient treatment regimen and highly active in NSCLC; myelosuppression is mild and rarely dose limiting. Most notably, paclitaxel appears to decrease carboplatin's pharmacodynamic effects on thrombopoiesis.
 ...
PMID:Preliminary results of a phase I/II clinical trial of paclitaxel and carboplatin in non-small cell lung cancer. 894 2

We have treated 26 consecutive chemotherapy-naive patients with stage IIIB/IV non-small cell lung cancer with an innovative regimen based on a 1-hour infusion of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 125 to 250 mg/m2, ifosfamide 3 g/m2 (with mesna), and carboplatin dosed to an area under the concentration-time curve of 5, every 21 days for a total of six cycles in responding or stabilized patients. Among 22 fully evaluable patients, 14 (64%) achieved a partial remission, six had disease stabilization, and two had disease progression. Hematologic toxicity was remarkably mild; only one patient had grade 3 neutropenia (on day 21). Arthralgias/myalgias (grade 3 in nine patients, grade 4 in one patient) and neurologic toxicity (a cumulative sensory neuropathy of grade 3 or 4 in five patients) were the most common side effects and seem to be dose related. To date, few patients are fully evaluable and survival data are clearly immature. Nevertheless, this regimen seems highly active and quite well tolerated, and deserves further evaluation.
 ...
PMID:Paclitaxel, ifosfamide, and carboplatin for the treatment of stages IIIB and IV non-small cell lung cancer: preliminary results. 933 Nov 26

To assess the feasibility of administering sequential cycles of dose-intensive therapy, 14 patients without prior chemotherapy for metastatic breast cancer were registered to be treated with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) at an initial dose of 250 mg/m2 over 24 hours (day 1), followed by carboplatin dosed to an area under the concentration-time curve of 16 (calculated according to the Calvert formula), every 3 weeks for four cycles. This combination was supported with peripheral blood stem cells collected following granulocyte colony-stimulating factor with or without cyclophosphamide and paclitaxel. One patient failed to peripheralize CD34 cells after cyclophosphamide/paclitaxel therapy and was taken off protocol. The remaining 13 patients entered the paclitaxel/carboplatin phase of the program, and nine completed all four cycles. The median duration of severe neutropenia (absolute neutrophil count < 100/microL) was 6 days, despite the absence of routine use of granulocyte colony-stimulating factor. Only five of a total of 42 chemotherapy cycles (12%) were associated with febrile neutropenia requiring hospitalization. Most patients did not require platelet transfusions. The most significant nonhematologic toxicity was gastrointestinal (grade 3 in three patients, two of whom had received local radiation for relapse before chemotherapy). Most patients developed grade 1 or 2 sensory neuropathy by the final cycle. Of the nine patients who entered the paclitaxel/carboplatin phase and were evaluable for response, five achieved a complete remission. This doublet of high-dose therapy can be given in an entirely ambulatory setting and is associated with modest hematologic toxicity. The value of this option in the treatment of metastatic breast cancer compared with more conventional approaches to high-dose therapy will require a greater number of patients evaluable for response and longer follow-up.
 ...
PMID:A phase II study of repetitive cycles of dose-intense carboplatin plus paclitaxel chemotherapy and peripheral blood stem cells in metastatic breast cancer. 937 1

The optimal dose and schedule for paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the treatment of patients with advanced breast cancer are not known. Based on our phase I study in non-small cell lung cancer, in which the dose intensity of paclitaxel was successfully escalated by using a weekly schedule, we initiated a phase II study of weekly paclitaxel in previously untreated patients with metastatic breast cancer (MBC) and locally advanced breast cancer (LABC). Treatment consists of weekly paclitaxel 175 mg/m2 intravenously over 3 hours for 6 weeks, followed by a 2-week break. Doses are modified for neutropenia (absolute neutrophil count < 1,500/microL), bilirubin levels greater than 1.5 times normal, or greater than grade 1 neuropathy. Patients with MBC continue treatment until disease progression. Patients with LABC receive one to two cycles before proceeding to surgery if resectable. Thus far, 15 patients, eight with MBC and seven with LABC, are assessable for response and/or toxicity. Most patients have required dose modification, with median delivery of 75% (cycle 1) and 50% (cycle 2) of the planned dose of paclitaxel. Neutropenia has been the most common cause of dose reductions, although only one patient required treatment for neutropenic fever. Six patients have developed grade 2/3 peripheral sensory neuropathy, but with dose reductions many have continued treatment with stable or improving neurologic symptoms. Objective responses have been seen in 12 of 14 assessable patients, including six with MBC (one complete response, five partial responses) and six with LABC (two complete responses, four partial responses), for an overall response rate of 86% (95% confidence interval, 66% to 96%). All responding LABC patients have been rendered free from disease at surgery. These preliminary results are very encouraging. Accrual to the study continues.
 ...
PMID:Weekly high-dose paclitaxel in metastatic and locally advanced breast cancer: a preliminary report. 937 2

The aim of this phase II study was to characterise the efficacy and toxicity of semisynthetic paclitaxel in patients with metastatic breast cancer. Eligible patients had measurable disease and had been treated with one prior chemotherapy regimen either as adjuvant or for metastatic disease. Semisynthetic paclitaxel was given at a dose of 175 mg/m2 over 3 h every 21 days with dexamethasone, cimetidine and diphenhydramine premedications. 31 patients were entered. All were evaluable for toxicity. 30 patients were evaluable for response because 1 patient was lost to follow-up after receiving one cycle. One patient achieved a complete response and 10 patients achieved partial responses for an overall response rate (CR + PR) of 37% (95% confidence interval 20-56%). 17 patients (55%) experienced at least one episode of grade 3 or 4 neutropenia. There were two episodes of febrile neutropenia complicating 155 cycles of therapy. One of these resulted in a treatment-related death in a patient with pulmonary metastasis. 3 patients required dose reductions for grade 3 sensory neuropathy. Our study shows that the antitumour activity and toxic effects of semisynthetic paclitaxel appear to be identical to the naturally occurring product.
 ...
PMID:Phase II study of semisynthetic paclitaxel in metastatic breast cancer. 947 Aug 6


1 2 3 4 5 6 7 8 9 Next >>