Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Taxol inhibits cell division by promoting the assembly and stabilization of microtubules. This report describes the results of a phase I trial of taxol administered as a short iv infusion daily for 5 days every 4 weeks. Sixteen patients with refractory malignancy received 21 courses of taxol at five doses between 5 and 40 mg/m2/day X 5. The first nine patients received taxol as a 60-minute infusion. Two patients experienced anaphylactoid reactions, one at the 5-mg/m2/day and the second at the 15-mg/m2/day X 5 dose levels. These reactions were characterized by facial flushing, tachypnea, and hypotension within several minutes of drug administration. These anaphylactoid reactions occurred on the first day of treatment in the first patient and on the first day of the second course in the second patient. These reactions may be related to the rapid administration of the polyoxyethylated castor oil (Cremophor EL) vehicle in which taxol is formulated. No anaphylactoid reactions were observed in the seven patients who received taxol as a 6-hour infusion with antihistamine and prednisone premedication. Dose-related myelosuppression was seen; leukopenia (wbc count less than 1000/mm3) and granulocytopenia (granulocytes less than or equal to 200/mm3) occurred on Days 8 and 9 in two of two patients treated at the 40 mg/m2/day X 5 level. Thrombocytopenia was mild, with a platelet nadir of 87,000-95,000/mm3 at the highest dose level. Premedication with glucocorticoids and antihistamines coupled with a prolonged 6-hour infusion permitted taxol to be administered at 30 mg/m2/day X 5 safely without immediate life-threatening reactions.
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PMID:Phase I study of taxol administered as a short i.v. infusion daily for 5 days. 289 42

From September 1993 through March 1994, 30 cases of refractory carcinoma of the ovary and Fallopian tube were treated with Taxol. Complete response was seen in 4 and partial response in 8 cases with a response rate of 40%. The average length of remission was 5 months in CR and 3.9 months in PR. The major toxic side effect was decrease in total white cell count and in neutrophil count. Apart from flushing of face during Taxol infusion in 6 patients, no other allergic reaction was observed. Gastrointestinal, neurologic, liver and renal toxicities were mild. Taxol is a drug of choice in the treatment of patients with cancer of the ovary and Fallopian tube who are resistant to conventional chemotherapy.
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PMID:[A clinical report of refractory carcinoma of ovary and fallopian tube treated with taxol]. 765 6

We tested paclitaxel (Taxol) and low dose hydroxyurea as second line therapy in 30 patients with non-small cell lung cancer since both drugs are active against non-small cell lung cancer in other settings, and since hydroxyurea may reverse chemotherapy resistance by disrupting double minute chromosomes. Hydroxyurea 500 mg was given orally each Monday, Wednesday, Friday starting 1 week before paclitaxel, and continuing until removal from study. Paclitaxel 135 mg/m2 was given i.v. over > or = 1 h every 3 weeks with dexamethasone, diphenhydramine, and ranitidine. Patients could have paclitaxel doses escalated to 175 mg/m2 in course 2 and to 200 mg/m2 in course 3, where tolerated. Sixteen males and 14 females were treated. All patients had previously received a single cisplatin-based chemotherapy regimen and 23 had previously received radiotherapy. Twelve patients had adenocarcinomas, six had squamous cell carcinomas, and 12 had large cell carcinomas. Eight patients had Stage IIIb cancers and 22 had Stage IV. Paclitaxel doses were 135 mg/m2 in 56 courses, 175 mg/m2 in 24, and 200 mg/m2 in 15. Treatment was well tolerated. Median granulocyte nadirs were 2.5 (x 10(9)/l) for paclitaxel 135 mg/m2, 1.8 for 175 mg/m2, and 1.3 for 200 mg/m2. No patient developed febrile neutropenia, and none required a dose reduction. Two patients had reversible anaphylaxis. Other toxicities were quite tolerable. They included fatigue, myalgias, dizziness, paresthesias, diarrhea, alopecia, mucositis, flushing, headache, swollen red hands, and anxiety. One patient had a partial remission and 15 had stable disease (including six with minor responses). Median survival was 20 (95% CI, 12-34) weeks, with 19% of patients remaining alive at 1 year from initiation of treatment. This is a well-tolerated regimen with modest activity as second line chemotherapy for patients with non-small cell lung cancer previously treated with cisplatin regimens. Higher doses would be feasible and other strategies are now being explored.
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PMID:Paclitaxel plus hydroxyurea as second line therapy for non-small cell lung cancer. 886 29

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.
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PMID:Preliminary results of a phase I/II clinical trial of paclitaxel and carboplatin in non-small cell lung cancer. 894 2

Registered nurses (RNs) and clinical pharmacists in the Hematology-Oncology Clinic at Walter Reed Army Medical Center conducted a descriptive study to determine the effectiveness and safety of using indwelling peripheral intravenous catheters (pics) for daily administration of various chemotherapeutic agents given intermittently over a 3-5 day period to outpatients. Eighty-nine adult outpatients requiring daily doses of chemotherapy including Fluorouracil (5-FU) (Solopak, Elk Grove Village, IL), Leucovorin (Immunex, Seattle, WA), Cisplatin (CDDP) (Bristol-Meyers, Princeton, NJ), Etoposide (VP-16), (Gensia, Irving, CA), Topotecan (SmithKline Beecham, Philadelphia, PA), or Taxol (Mead Johnson, Princeton, NJ), plus antiemetics were studied. Vialon 20-, 22-, or 24-gauge indwelling PICs (Becton Dickinson, Sandy, UT), were placed. Approximately 80% of patients successfully completed treatment with the original PIC in place. Daily flushing of the PIC with 2 ml [corrected] of Heplock U100 (Elkins-Sinn, Cherry Hill, NJ), maintained Heplock patency.
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PMID:Use of an indwelling peripheral catheter for 3-5 day chemotherapy administration in the outpatient setting. 906 Mar 58

Paclitaxel (Taxol) a taxane antineoplastic agent causing irreversible microtubule aggregation with activity against breast, ovarian, lung, head and neck, bladder, testicular, esophageal, endometrial and other less common tumors was derived from the bark of the Pacific yew (Taxus brevifolia). Phase I trials conducted in the late 1980s were almost halted because of the high frequency of hypersensitivity-like reactions. Respiratory distress (dyspnea and/or bronchospasm), hypotension, and angioedema were the major manifestations, but flushing, urticaria, chest, abdomen, and extremity pains were described also. Reactions occurred on first exposure in the majority of cases raising etiologic questions. The vehicle for paclitaxel Cremophor EL (polyoxyethylated castor oil in 50% ethanol) was strongly suspect as a direct (non-immunoglobulin E dependent) histamine releaser. Premedication regimens and longer infusion times lowered the incidence of reactivity allowing phase II and III trials to progress through the early 1990s. The mechanism(s) underlying paclitaxel hypersensitivity-like reactions is still unknown, and clinical data on probable complement and mast cell activation are lacking. The original clinical trial protocols for paclitaxel required discontinuation of therapy for patients who experienced hypersensitivity-like reactions. Here, we review the current etiologic knowledge of these reactions and describe our clinical approach to allow completion of chemotherapy with this powerful plant-derived agent.
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PMID:Taxol reactions. 1212 9