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)

Based on results of a phase I study demonstrating antitumor activity of taxol in patients with melanoma, 34 patients with documented metastatic melanoma received taxol, 250 mg/m2, as a 24-hours infusion, repeated every 21 days, in this phase II study. All patients received premedication with dexamethasone, diphenhydramine and cimetidine. Four patients experienced anaphylactic reactions and stopped treatment. Other significant toxicity of this drug included short-lived but severe neutropenia (less than 1,000/mm2) and peripheral neurotoxicity. Four of 28 evaluable patients demonstrated objective response (14%) (confidence interval, 4%-33%) including 3 complete responses and 1 partial response. Two complete responders are continuing at 25+ and 38+ months after achieving CR. Minor evidence of anti-tumor activity was noted in five additional patients. Taxol has significant activity in melanoma and should be further studied in combination with other agents in this disease.
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PMID:A phase II study of taxol in patients with malignant melanoma. 167 65

Taxol, an antimicrotubule agent, has shown promise for efficacy in treatment of breast cancer, but severe hypersensitivity reactions led to cessation of many phase I clinical trials. Consequently, investigators and the National Cancer Institute recommended that phase I and II studies of this agent use 24-hour infusions and antiallergic medications. Using a premedication regimen effective in preventing hypersensitivity reactions, we have performed a phase II trial of taxol in patients with metastatic breast cancer. Taxol was administered to 25 patients at a dose of 250 mg/m2 by 24-hour infusion every 21 days. These patients had received only one prior chemotherapy regimen, either adjuvant to surgery or for metastatic disease; all but two had received doxorubicin. In 60% of the patients, the dominant site of disease was the viscera. All patients were assessable. In April 1991, at a median time on study of 9 months (range, 5-13+ months), the objective response rate was 56% (12% complete and 44% partial; 95% confidence interval, 35%-76%). Disease progressed in only 8% of the patients. The median number of courses of therapy was 11. Granulocytopenia was the dose-limiting toxic effect, but neutropenia with fever occurred in only 5% of 232 courses. A chronic glove-and-stocking neuropathy developed in most patients, but no allergic reactions occurred. We conclude that taxol is an active agent in the treatment of metastatic breast cancer and that it warrants continued study. Currently, we are conducting a phase I trial of taxol plus doxorubicin. Future trials should address the optimal effective dose, the optimal sequencing of combinations, mechanisms of drug resistance in tumors, and dose-limiting toxic effects (particularly cardiac toxic effects of taxol given as a single agent or in drug combinations).
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PMID:Phase II trial of taxol, an active drug in the treatment of metastatic breast cancer. 168 8

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.
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PMID:Taxol: an important new drug in the management of epithelial ovarian cancer. 168 43

Taxol is an investigational new drug which is currently undergoing Phase II evaluation in various tumors. It is a plant alkaloid extracted from the western Yew, Taxus brevifolia. In this study, patients with metastatic melanoma who were previously untreated, received Taxol at a starting dose of 250 mg/m2 delivered as a continuous intravenous (IV) infusion over 24 hours, at 3-week intervals. All patients were premedicated with oral dexamethasone and IV diphenhydramine hydrochloride as prophylaxis against allergic reactions. Three of 25 patients had a partial response (PR) for a response rate of 12% (CI, 3%-31%). In addition four patients had objective regression of tumor that failed to qualify for a PR but these responses were as durable, lasting 6 to 17 months. No patient experienced acute allergic reactions. The major toxicity of Taxol was neutropenia requiring dose reduction to 200 mg/m2 in a majority of the patients. Our data confirm that Taxol has definite although limited activity against metastatic melanoma.
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PMID:A phase II trial of taxol in metastatic melanoma. 197 Sep 48

Taxol, a plant product, has significant activity against certain rodent and human xenograft tumors. It promotes microtubule assembly in vitro, in contrast to vinca alkaloids, which inhibit assembly. In this phase I study, taxol was administered as a 24-hour continuous intravenous (IV) infusion in 65 courses to 26 patients. A premedication regimen of dexamethasone, cimetidine, and diphenhydramine was used to prevent the acute hypersensitivity reactions observed in previous studies of taxol. Only one episode of mild stridor occurred in this study. Peripheral neuropathy was the dose-limiting toxicity and was observed in 40% of patients treated at a dose of 250 mg/m2. Significant neutropenia of brief duration was also common. Pharmacokinetic studies by a high-performance liquid chromatography (HPLC) method demonstrated that drug plasma concentrations increased during the 24-hour infusion and then declined rapidly. Peak plasma concentrations correlated with dose, and less than 5% of taxol was excreted in the urine. Most of the drug was bound to serum components. Partial responses of more than 3 months' duration were observed in four of 12 melanoma patients treated. The recommended phase II dose of taxol on this schedule is 250 mg/m2. Priority should be given to the study of taxol in melanoma.
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PMID:Phase I trial of taxol given as a 24-hour infusion every 21 days: responses observed in metastatic melanoma. 288 41

The University of Colorado Cancer Center is conducting a phase I study of the three-drug PET combination of cisplatin, etoposide, and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in patients with advanced (stage IV or IIIB with pleural effusion) small cell lung cancer. The primary study goal was to define the maximally tolerated doses given on an outpatient basis. Secondary goals were to determine toxicities, response rate, response duration, and survival. Paclitaxel was given as a 3-hour intravenous (IV) infusion prior to cisplatin and etoposide. The starting doses were paclitaxel 135 mg/m2 day I, cisplatin 80 mg/m2 IV day I, and etoposide 50 mg/m2 IV day I, and 100 mg/m2 orally days 2 and 3, every 3 weeks. In the second group, the etoposide was increased to 80 mg/m2 IV day I and 160 mg/m2 orally days 2 and 3. In the third group, paclitaxel was increased to 175 mg/m2 IV day I. Granulocyte colony-stimulating factor was not given on the first cycle, but was given on subsequent cycles if grade 4 neutropenia developed. So far, 13 patients have been entered on the study; all are evaluable for toxicity and nine are evaluable for response. The major toxicity was neutropenia, with no other grade 4 toxicities observed. All patients received the full six cycles of therapy. Thus far, partial responses have been observed in four patients (44%) and complete responses in five patients (56%), for an overall response rate of 100%. This ongoing study has shown that full doses of each of these three active drugs can be administered safely on an outpatient basis. The encouraging early results should lead to a multicenter phase II evaluation of the PET combination.
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PMID:A phase I study of cisplatin, etoposide, and paclitaxel in small cell lung cancer: a University of Colorado Cancer Center study. 748 62

Current chemotherapeutic approaches to recurrent head and neck cancer have routinely yielded response rates of 10% to 30% (for single agents) and 30% to 50% (for combination chemotherapy). However, median survival times for patients with metastatic and/or recurrent disease have stagnated at around 6 months since the 1970s. The investigation of new drugs and treatment approaches thus continues to be a high priority. One such agent, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), has shown good single-agent activity and is also believed to potentiate the effects of radiation therapy in patients with head and neck cancer. We have focused on the addition of paclitaxel to the previously established combination of 5-fluorouracil, hydroxyurea, and radiation therapy. The study goals are to establish the maximum tolerated dose and dose-limiting toxicity of paclitaxel when added to this combination as a 5-day continuous infusion on a biweekly schedule. Preliminary results of this ongoing study have demonstrated activity in patients with poor-prognosis head and neck cancer. Major dose-limiting toxicities have consisted of neutropenia and mucositis, and definition of a recommended phase II dose is in progress.
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PMID:The role of paclitaxel in the treatment of head and neck cancer. 748 66

We have developed a regimen incorporating multiple cycles of high-dose carboplatin and fixed-dose paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) with granulocyte colony-stimulating factor and peripheral blood stem cell support given every 21 days for up to four cycles. Our phase I study of this regimen has treated 26 patients with good performance status and histologically documented unresectable or metastatic carcinoma, sarcoma, or melanoma, 21 of whom received all planned courses every 21 days. Paclitaxel 250 mg/m2 was infused over 24 hours, followed by a 1-hour carboplatin infusion, with doses escalated between area under the concentration-time curve (AUC) targets of 8 and 20. Considering the carboplatin doses administered (two to three times those generally achieved with growth factor support), toxicity has been relatively modest. The median duration of grade 4 neutropenia and thrombocytopenia was not significantly different between the AUCs of 8 and 18, which proved to be the maximum tolerated carboplatin dose. Twelve courses were associated with hospitalization for neutropenic fever or catheter-related thrombophlebitis. One treatment-related death occurred, and severe toxicity caused withdrawal of two patients treated at the AUC of 20. Peripheral neuropathy was the most common serious nonhematologic complication. Pharmacokinetic analysis showed significantly lower measured versus predicted AUC values. Among 25 evaluable patients, preliminary results show one complete response (ovarian cancer) and 11 partial responses, including four in patients with non-small cell lung cancer. Additional issues to be addressed include the effect of a shorter (or longer) paclitaxel infusion on the carboplatin AUC (and the incidence of toxicity) and whether the discrepancy between actual and predicted AUCs (greater in our study than reported elsewhere) is due to the variability of creatinine clearance-determined glomerular filtration rate or to altered carboplatin pharmacokinetics when a short high-dose infusion follows paclitaxel. Additional patients are being accrued at the AUC of 18.
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PMID:A clinical and pharmacokinetic study of high-dose carboplatin, paclitaxel, granulocyte colony-stimulating factor, and peripheral blood stem cells in patients with unresectable or metastatic cancer. 748 67

Epithelial ovarian cancer is the fifth most common cause of cancer death in women. The management of patients with advanced disease involves surgery followed by platinum-based chemotherapy, but most patients will have either residual or recurrent disease. Salvage therapy in these patients is poor, with response rates less than 20%. Taxol, a new antineoplastic agent, was first noted to have activity in platinum-resistant ovarian cancer in a phase I study. Since then, response rates of 20% to 35% have been noted in several phase II studies involving hundreds of patients. Major toxicities include neutropenia and peripheral neuropathy. Taxol dose escalation with granulocyte-colony stimulating factor support, and Taxol in combination with cisplatin, have been tested and shown to be feasible. Intraperitoneal administration of Taxol is possible and appears advantageous from a pharmacokinetic perspective. A phase III study of Taxol and cisplatin in suboptimal disease was completed, and toxicity data show that Taxol administration is safe in a multi-institutional setting. Planned clinical development of Taxol includes use in less bulky stage III disease and dose escalation in platinum-resistant disease. Taxol has already become a major treatment of platinum-resistant disease. Further investigation will determine its role in the overall management of ovarian cancer.
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PMID:Taxol in epithelial ovarian cancer. 751 52

Twenty-eight patients received Taxol as their first chemotherapy for stage IV breast cancer. An additional 51 patients with extensive prior exposure to other chemotherapeutic agents received Taxol as salvage therapy. We found significant activity for the drug in both situations, as well as a strong clinical suggestion of non-cross-resistance with doxorubicin. An excellent response in previously irradiated skin was noted in one case. The routine use of recombinant human granulocyte-colony stimulating factor seemed to ameliorate some of the dose-limiting toxicity of neutropenia. Other toxicity was mild to moderate in most cases. With further development, Taxol should play a significant role in the systemic management of breast cancer.
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PMID:Taxol plus recombinant human granulocyte-colony stimulating factor as initial and as salvage chemotherapy for metastatic breast cancer: a preliminary report. 751 53


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