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)

This phase I/II study was done to evaluate the safety and feasibility of two schedules of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) administered by 1-hour infusion in the outpatient setting. Fifty-six patients with advanced, refractory malignancies received one of two paclitaxel schedules by random assignment: 135 mg/m2 given as a single dose over 1 hour or 135 mg/m2 given in divided hourly daily doses for 3 days. All patients were premedicated with dexamethasone, diphenhydramine, and cimetidine. No serious acute hypersensitivity reactions were seen with either schedule of paclitaxel. Other adverse effects were usually mild and easily tolerated. Other than alopecia, which was universal, myelosuppression was the most common severe toxicity. However, grades 3 and 4 leukopenia occurred in only 19% and 2% of treatment courses, respectively. Nine patients required hospitalization for treatment of fever associated with neutropenia. There were no significant differences in toxicity observed when comparing the two paclitaxel regimens. It is too early to adequately assess tumor response, but thus far 11 of 56 patients (20%) had partial or complete response to therapy. Responses were observed in patients with breast, ovarian, and lung cancers. Paclitaxel can be safely given by 1-hour infusion in the outpatient setting, both as a single dose and in divided doses for 3 days. Severe acute hypersensitivity reactions did not occur in 162 courses. Neutropenia was mild in most patients and severe thrombocytopenia was rare. The use of this dose and these schedules of paclitaxel as a component of combination chemotherapy regimens should be possible. Investigation of paclitaxel at 200 mg/m2 given by 1-hour infusion is currently in progress.
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PMID:Paclitaxel (Taxol): phase I/II trial comparing 1-hour infusion schedules. 793 60

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given as a 24-hour infusion, and carboplatin have activity in advanced non-small cell lung cancer (NSCLC) and ovarian cancer. Two dose-finding studies were initiated to identify the optimal doses for the paclitaxel/carboplatin combination when paclitaxel is given in a 3-hour infusion. The fact that the pharmacologic interaction between paclitaxel and cisplatin increases the toxicity of paclitaxel when cisplatin is given before it also prompted an investigation of the influence of drug sequence on toxicity and pharmacokinetics in the NSCLC trial. Thirty-three patients with advanced NSCLC and 11 with advanced ovarian cancer previously untreated by chemotherapy have been enrolled to date. In the NSCLC trial escalating doses of paclitaxel were given in combination with a fixed carboplatin dose of 300 mg/m2, while both drugs were escalated in the ovarian cancer study. In both studies paclitaxel was infused over 3 hours and carboplatin over 30 minutes, and cycles were repeated every 4 weeks. The most frequent side effect has been neutropenia, although this did not result in any infectious episodes. Alopecia and mild emesis also have been frequently encountered. Mild skin reactions have been reported in a few patients. Bone pain and myalgia occur more frequently at the highest paclitaxel doses. No difference in toxicity has been observed thus far between the two drug sequences in the NSCLC study. Both studies are still accruing patients as the maximum tolerated doses of paclitaxel in combination with carboplatin have not yet been reached (carboplatin 300 mg/m2 with paclitaxel 175 mg/m2 in the NSCLC study; carboplatin 400 mg/m2 with paclitaxel 150 mg/m2 in the ovarian cancer study). An investigation of maximum tolerated doses with granulocyte colony-stimulating factor support is planned thereafter.
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PMID:Preliminary results of two dose-finding studies of paclitaxel (Taxol) and carboplatin in non-small cell lung and ovarian cancers: a European Cancer Centre effort. 793 61

We present preliminary results of a study undertaken in previously untreated patients with non-small cell lung cancer to determine the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) when administered as a 3-hour intravenous infusion in combination with cisplatin every 3 weeks; to evaluate the nature, frequency, severity, and duration of adverse events associated with this drug combination; and to evaluate the combination's antitumor efficacy. Thus far, we have treated 10 patients with cisplatin (100 mg/m2) and increasing doses of paclitaxel (135, 170, and 200 mg/m2). Among nine evaluable patients, four partial responses have been obtained, disease in three patients progressed after three courses, and no changes were seen in one patient. One patient had two cardiac arrests within 8 days of the onset of therapy, from which he recovered; he died 1 month later of massive hemoptysis. Thrombocytopenia was not seen in these patients, and neutropenia (< 1,000 granulocytes/microL) was seen in only three patients. Infections were seen in these patients and were manageable in all cases. Other toxicities consisted mainly of World Health Organization grades II and III alopecia and nausea and/or vomiting. No grade III nephrotoxicity, neurotoxicity, hypersensitivity, mucositis, or infection was seen in this series after one to three courses of chemotherapy; one patient presented with grade IV cardiotoxicity 6 days after the onset of therapy. So far, the maximum tolerated dose of the cisplatin/paclitaxel combination has not been reached; however, definitive conclusions await the full treatment of additional patients. Moreover, the possibility of cumulative and delayed toxicity must be evaluated after a sufficient duration of follow-up in adequate numbers of patients.
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PMID:Dose-finding study of paclitaxel (Taxol) plus cisplatin in patients with non-small cell lung cancer. 793 62

The mainstay of treatment for head and neck cancer patients with recurrent disease has been chemotherapy with cisplatin/5-fluorouracil or methotrexate. Clearly, new drugs are needed to improve response rates and prolong survival. One new chemotherapeutic agent that has shown activity in head and neck cancer, as well as other tumor types, is paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ). In a recently completed phase II trial in patients with recurrent head and neck cancer, the complete and partial response rate to high-dose paclitaxel (250 mg/m2) given as a 24-hour infusion with granulocyte colony-stimulating factor support was 40% (12 of 30 patients). The principal toxicities were similar to those reported in other trials: neutropenia, peripheral neuropathy, and arthralgias/myalgias. Other single-agent trials with paclitaxel currently are in progress, as are trials of paclitaxel--containing combination therapy using cisplatin, carboplatin, ifosfamide, and/or methotrexate. Also under evaluation are paclitaxel combined with radiotherapy and given in lower doses and alternative infusion schedules. Findings, to date suggest that paclitaxel may be the most active single chemotherapeutic agent for the treatment of head and neck cancer.
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PMID:Paclitaxel (Taxol) for the treatment of head and neck cancer. 793 63

A multinational, randomized study has been conducted to compare the effectiveness and safety of two doses of Taxol (paclitaxel) (135 and 175 mg/m2, given as a 3-hour intravenous infusion every 3 weeks) in patients with metastatic breast carcinoma who had previously undergone treatment with one or two chemotherapeutic regimens. A total of 471 patients were enrolled in the study; the first 117 were included in an interim analysis that was planned in the protocol to identify any extreme efficacy differences between the treatment arms. Most (85%) of these initial patients were ambulatory with a performance status of 0 or 1 and multiple sites of disease. Duration of treatment ranged from 1 to 7 courses (median, 4). Of the 113 patients who received Taxol 135 mg/m2 (n = 56) or 175 mg/m2 (n = 57), 111 were evaluable for an overall response rate of 27%, with 3 complete and 27 partial responses. In this interim analysis no significant difference in response rate between the two treatment groups was detected. The primary toxicity encountered was neutropenia that was rapidly reversible and not associated with treatment delays. It was concluded that at these doses Taxol is an effective and well-tolerated treatment option for the management of metastatic breast cancer in previously treated patients.
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PMID:Taxol (paclitaxel) in patients with metastatic breast carcinoma who have failed prior chemotherapy: interim results of a multinational study. 797 May 6

Taxol (paclitaxel) has demonstrated good antitumor activity against metastatic breast cancer (MBC) in phase II trials. The drug is usually well tolerated. However, severe myelosuppression, including rapidly reversible neutropenia, may necessitate dose reductions and may ultimately limit its use as a long-term treatment. Sequential or simultaneous administration of Taxol and doxorubicin may enhance response rates. There appears to be no complete cross-resistance between the two drugs. Current trials are exploring the best way to deliver this combination while keeping dose-limiting toxicity to a minimum. Additionally, single-agent trials are evaluating Taxol in extensively pretreated MBC. The results of these trials are awaited with interest.
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PMID:Use of Taxol (paclitaxel) in breast cancer. 797 May 7

Taxol is a structurally complex natural plant product with a novel mechanism of action. The supply of this drug is limited by its low abundance in the bark of the slow-growing yew tree from which it is extracted. The chemical complexity of taxol has hampered the development of a feasible process to synthesize large quantities. Analogues are being made from a precursor found in the needles of the yew tree. However, there is a need to develop a more efficient method to provide adequate supplies of this drug. This review article summarizes the preclinical and clinical studies of taxol in ovarian cancer. Phase I studies have identified the drug's toxicities. Neutropenia has been the dose-limiting toxicity in most trials, and premedications and longer infusion schedules have been used to reduce the incidence and severity of hypersensitivity reactions. The intraperitoneal administration of taxol in Phase I studies showed a pharmacologic advantage with acceptable toxicity. Its activity in ovarian cancer was noticed first in Phase I trials at the Albert Einstein College of Medicine and Johns Hopkins University. These observations led to Phase II testing, which documented response rates of 20-35% in patients with relapsed or refractory ovarian cancer. Phase III trials of taxol and cisplatin versus cyclophosphamide and cisplatin in untreated patients with ovarian cancer are in progress. Studies combining taxol with colony-stimulating factors and cisplatin are ongoing. Taxol is an important new drug in ovarian cancer. Its unique mechanism of action and toxicities make it an attractive agent to use in combination with currently active drugs. Future studies will determine the role of taxol in the management of this disease, but the widespread availability of this drug will depend on the development of a feasible synthetic process.
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PMID:Taxol in ovarian cancer. 809 22

Taxotere (N-debenzoyl-N-tert-butoxycarbonyl-10-deacetyl Taxol; RP 56976; NSC 628503) is a semisynthetic analogue of Taxol. It is twice as active in inhibiting tubuline depolymerization and has a better in vivo activity on B16 melanoma, with responses in advanced colon 38 and PO3 adenocarcinoma. Sixty-five patients (49 women, 16 men), with a median age of 57 years, received 248 courses of Taxotere given as a 1-2-h i.v. infusion every 2 or 3 weeks. Ten distinct dose levels from 5 to 115 mg/m2 were studied. Dose-dependent, reversible neutropenia was the limiting toxicity. Delayed and cumulative skin reactions occurred beyond 70 mg/m2. Alopecia was observed in the majority of patients beyond 70 mg/m2. Four partial responses were achieved in patients with ovarian carcinoma, breast carcinoma, small cell lung cancer, and carcinoma with unknown primary. The pharmacokinetics of Taxotere, determined in 23 patients receiving 20 to 115 mg/m2, was linear. At the highest doses, the Taxotere plasma profile was typically triphasic, with a terminal half-life of 13.5 +/- 7.5 (SD) h, a plasma clearance of 21.1 +/- 5.3 liters/h/m2, and a distribution volume of 72 +/- 40 liters/m2. AUC correlated with the percentage decrease of neutrophils in a sigmoid Emax model. The renal excretion of unchanged Taxotere was very low (< 5% of the dose). The recommended dose for phase II trials with this schedule is 100 mg/m2 every 3 weeks.
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PMID:Phase I and pharmacokinetic study of Taxotere (RP 56976; NSC 628503) given as a short intravenous infusion. 809 96

A dose-finding study was performed in 27 ovarian cancer patients to define the maximum tolerated dose of a 3-hour infusion of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in combination with a fixed dose of carboplatin. The median age of the patients was 55 years (age range, 30 to 74 years), the median performance status was 0 (range, 0 to 2), and the sizes of tumors residual to first surgery were identified as > or = 1 cm (14 patients) or less than 1 cm (13 patients). All patients received carboplatin at a fixed dose of 300 mg/m2 over 1 hour. Paclitaxel was administered as a 3-hour infusion at five dose levels, starting at 150 mg/m2 and increasing in 25 mg/m2 increments to 250 mg/m2. In the absence of toxicity, courses were repeated every 4 weeks for a total of six cycles. Mild emesis, general alopecia, and moderate myalgias occurred. Hypersensitivity and cardiotoxicity were observed in 7.4% and 14.8% of patients, respectively. Moderate peripheral neuropathy was experienced by 30% of patients. Grade 3 and 4 neutropenia lasted less than 7 days; no patients required hospitalization for sepsis or febrile neutropenia, and no supportive treatment with granulocyte/granulocyte-macrophage colony-stimulating factor was needed. Twenty-one patients were evaluable for response. Overall response rate (complete response+partial response) was 81%, and responses were observed at all paclitaxel dose levels. The maximum tolerated dose was not achieved. In conclusion, with a fixed dose (300 mg/m2) of carboplatin, paclitaxel can be administered by 3-hour infusion at 250 mg/m2 with manageable toxicity and no supportive care is needed.
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PMID:Pilot study with fixed-dose carboplatin and escalating paclitaxel in advanced ovarian cancer. 855 81

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


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