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)

Taxol is the first of the taxanes, a new class of cytotoxic agents whose cellular target is the microtubules network. Taxol induces the polymerisation of the alpha and beta sub-units of the tubulin. This mechanism of action which is different from the vinca-alkaloids explains the main cytotoxic activity of paclitaxel through the formation of abnormal and stable bundles of microtubules. Severe hypersensitivity reactions which were seen in early phase I studies are prevented by an oral corticosteroids and H1 and H2 blockers premedication. Profound neutropenia is frequent but of short duration explaining that infectious manifestations are rare and neutropenia not cumulative. Thrombopenia and anemia are rare. Neurotoxicity is dose related but severe peripheral neuropathy is rare. Conduction abnormalities are mainly asymptomatic bradycardias. In second line ovarian cancer and breast metastatic cancer a noticeable level of activity has been observed, and in lung and head and neck cancer Taxol has proved to be effective.
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PMID:[Taxol (paclitaxel), first molecule of a new class of cytotoxic agents: taxanes]. 789 25

Taxol, a new and novel antimicrotubule agent, has shown clear activity as a salvage therapy in epithelial ovarian carcinoma. More importantly, it is active in tumors that have displayed resistance to platinum compounds. Its role as part of initial therapy in combination with cisplatin in advanced disease is currently being explored but data are too immature for any conclusions. Its major and dose-limiting toxicity is neutropenia which makes it an ideal drug to escalate with cytokines although, to date, no clear dose-response relationship has been identified. Taxol may well be the most important new antineoplastic agent to surface in the past decade as further studies suggest it has broad antitumor activity. Studies conducted over the next several years will more clearly place this drug in its proper role in the treatment of ovarian cancer as well as other tumors in which early trials suggest definite activity.
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PMID:Taxol: a new drug with significant activity as a salvage therapy in advanced epithelial ovarian carcinoma. 790 14

Taxol is a cytostatic agent of plant origin with a complex structure and a special mode of action. Owing to the small content of this substance in the bark of the Pacific yew, from which Taxol is derived, it has only been available on a limited scale. Hitherto, Taxol's chemical structure has precluded the synthesis of large quantities of this cytostatic agent. Analogue substances can be obtained from the needles of the yew, although more efficient methods are needed for the manufacture of this medicine on a commercial scale. The present paper summarises the results of preclinical and clinical studies of patients suffering from ovarian and breast cancer. In phase I studies, it was possible to delineate the side effect profile of Taxol, neutropenia being dose-limiting in most investigations. The efficacy of Taxol on patients with ovarian cancer was initially demonstrated in phase I studies. These results led to phase II studies, in which response rates of 20-36% were obtained on patients with relapsing or therapy-refractory ovarian carcinomas. In phase III studies, the efficacy of Taxol combined with cisplatinum is currently being compared with the classical regimen of cisplatinum/cyclophosphamide. Further studies are under way testing Taxol in combination with G-CSF and cisplatinum. As a supplement to intravenous Taxol therapy, initial experience with intraperitoneal Taxol treatment is now available. Taxol's cytostatic efficacy has also been confirmed in the treatment of patients suffering from metastatic breast cancer with remission rates of 56-62%. Taxol is an important new cytostatic agent for the treatment of ovarian and breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Taxol--a new cytostatic drug for therapy of ovarian and breast cancer]. 791 12

Paclitaxel, a compound derived from the bark of the Pacific yew, Taxus brevifolia, is an antimitotic cytotoxic agent with a mechanism of action different from other antimitotics such as vincristine and vinblastine. Instead of causing disassembly of microtubules, paclitaxel forms extremely stable and nonfunctional microtubules, which causes inhibition of many cell functions and the interruption of the cell cycle. Procurement of paclitaxel has raised environmental concerns, leading researchers to explore a variety of approaches to obtain the drug: extraction from yew needles of a paclitaxel precursor that can be converted to paclitaxel, genetic manipulation of plants to increase yield, propagation of yew trees, semisynthesis, total chemical synthesis, and paclitaxel-producing fungus. Clinical trials involving paclitaxel have demonstrated antineoplastic effects in several classically refractory tumors: ovarian cancer, breast cancer, non-small-cell lung cancer, and head and neck tumors. Several toxic effects have been attributed to paclitaxel, including hypersensitivity reactions, cardiotoxicities, neutropenia, peripheral neuropathy, mucositis, gastrointestinal toxicities, alopecia, arthralgias, and myalgias. Clinical implications for these toxicities are addressed.
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PMID:Paclitaxel: a new antimitotic chemotherapeutic agent. 791 53

At the low-to-moderate doses that are recommended, paclitaxel is a well-tolerated drug. Although adverse reactions do occur, most of these are manageable and do not have a long-lasting effect on the patients' quality of life. The starting dose of paclitaxel, as approved by the Food and Drug Administration for refractory ovarian cancer, is 135 mg/m2. A slightly higher dose (175 mg/m2) is being investigated for heavily pretreated patients with metastatic breast cancer. In the investigational setting, the highest dose that may safely be administered when paclitaxel is used as a single agent is 250 mg/m2 for minimally pretreated patients. If G-CSF is also given, the same dose may safely be administered to heavily pretreated patients. When paclitaxel is administered in combination with cisplatin, a dose of 135 mg/m2 may safely be given prior to cisplatin, which is administered at a dose of 75 mg/m2. These dose levels may be increased when G-CSF is also used. Dose modifications should be considered only in patients who experience severe neutropenia or neurotoxicity. Patients who received high doses of paclitaxel in Phase II trials frequently required dose reductions. However, when the drug is administered at the recommended dose of 135 mg/m2, neutropenia does not often necessitate further dose reduction. Hematopoietic growth factors, such as G-CSF, seem to be helpful in preventing prolonged grade IV and febrile neutropenia, and in avoiding treatment delays for longer than one week.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Patient care issues: the management of paclitaxel-related toxicities. 791 56

Two trials are being conducted to evaluate paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) combined with cisplatin in previously treated and untreated breast and ovarian cancer. Preliminary results are presented. The objectives of these nonrandomized trials are (1) to determine the toxicity of paclitaxel/cisplatin in a biweekly schedule, (2) to establish the maximum tolerated dose of paclitaxel in combination with a fixed dose of cisplatin (60 mg/m2), (3) to determine the feasibility of repeated biweekly administrations, and (4) to evaluate the efficacy of the combination in these diseases. In the breast cancer study, 22 patients have been enrolled to date and eight patients have completed treatment. Dose-limiting neutropenia, which occurred with the starting dose of paclitaxel (90 mg/m2) followed by 60 mg/m2 cisplatin, has precluded any attempts to escalate the paclitaxel dose. Overall, the regimen has been well tolerated at the doses just described. There has been little grade III and no grade IV nonhematologic toxicity. Among 16 patients currently evaluable for response, four had a complete response and II had a partial response, for an overall response rate of 94%. In the ovarian cancer study, 14 patients have been enrolled thus far. Paclitaxel/cisplatin appears to be well tolerated, although it is still too early to assess response rates or to define the MTD. Patients continue to be accrued in both trials.
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PMID:Biweekly paclitaxel (Taxol) and cisplatin in breast and ovarian cancer. 793 58

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 conducted a multicenter Phase II study of BMS-181339 in patients with ovarian cancer. The facilities participating were 23 in number. The total number of cases registered for the study were 62; 57 of them entered for evaluation in drug efficacy, and 58 cases were evaluable in drug safety. All the cases were previously treated with chemotherapy including platinum-based drugs. The clinical responses of BMS-181339 were as follows: CR, 1 case; PR, 13 cases; MR, 3 cases; NC, 13 cases and PD, 27 cases. The response rate was 24.6% (95% CI: 14.1-37.8%). Histologically, the drug showed its efficacy on serous adenocarcinoma 28.2% (11/39), mucinous adenocarcinoma 20.0% (1/5) and clear cell adenocarcinoma 20.0% (1/5). In regional evaluation, the drug demonstrated its efficacy not only on endopelvic lesions 19.0% (4/21) and abdominal lesions 14.3% (2/14), but also on remote metastatic lesions such as hepatic metastasis 30.8% (4/13) and lung/pleura 33.3% (2/6). The drug also showed its efficacy on the cases 22.9% (8/35) refractory to the platinum-based drugs. Major adverse reactions were fever 63.8% (37/58), alopecia 59.3% (32/54), peripheral nerve disorders 28.1% (16/57) such as numbness of the extremities, nausea/vomiting 24.1% (14/58), arthralgia 20.7% (12/58) and diarrhea 20.7% (12/58) etc.. Abnormal alterations in laboratory test values were an incidence rates of 100% for both leukopenia and neutropenia. However, these symptoms were clinically manageable by transient withdrawal of medication, dose reduction and administration of antibiotics and G-CSF. In addition, decrease in hemoglobin 93.1% (54/58), decrease in platelet counts 31.0% (18/58), elevation in GOT 27.6% (16/58), in GPT 31.0% (18/58) and in LDH 20.7% (12/58) were seen, but no serious organopathy was observed. Thus, we confirmed that BMS-181339 was a clinically useful chemotherapeutic agent in patients with ovarian cancer.
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PMID:[A phase II study of BMS-181339 in patients with ovarian cancer. BMS-181339 Ovarian Cancer Study Group]. 794 92

Eight evaluable patients with cisplatin-resistant non-small cell lung cancer (6 patients), small cell lung cancer (1 patient), or both breast and ovarian cancer (1 patient) were entered on a study to determine whether the addition of nifedipine plus pentoxifylline to cisplatin-based chemotherapy would result in increased chemotherapy efficacy. No patient responded to treatment. Myelosuppression may have been augmented by the nifedipine and pentoxifylline (median granulocyte nadir, 0.3 x 10(9)/L). Two patients developed febrile neutropenia. Nifedipine and pentoxifylline had to be stopped in two evaluable patients due to hypotension, and three additional inevaluable patients withdrew from the study due to nifedipine-pentoxifylline toxicity before receiving their chemotherapy. There was no indication that other types of chemotherapy toxicity were increased by the addition of nifedipine and pentoxifylline. A major problem with the strategy followed in this protocol was that patients whose tumors had failed to respond to cisplatin-based regimens were often too ill to tolerate additional cisplatin, particularly when accompanied by nifedipine-associated hypotension.
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PMID:Addition of pentoxifylline plus nifedipine to chemotherapy in patients with cisplatin-resistant cancers of the lung and other sites. 804 93

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


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