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)

Paclitaxel (Taxol; Bristol-Myers Squibb Company; Princeton, NJ) is an antineoplastic agent that inhibits microtubular function and has shown efficacy in several solid tumors, mainly ovarian tumors, in which 20% to 40% response rates in previously treated patients were observed. We conducted a study to assess survival, response rate, and toxicity associated with paclitaxel treatment in patients with advanced ovarian cancer resistant to platinum therapy. Between September 1994 and November 1996, 38 patients were admitted for study and 37 were evaluable. All had disease progression or relapse within 1 year of receiving platinum-containing first-line chemotherapy. Mean age was 59 years (range, 30 to 75 years), all had bulky disease, and 18 showed increased carbohydrate antigen-125 at admission. They were treated every 3 weeks with paclitaxel 175 mg/m2 as a 3-hour infusion, preceded by standard premedication. Response rate was 51.3%, with a median response duration of 10.0 months and a median survival rate of 16.8 months. Mild to moderate hematologic toxicity was observed with only one episode of grade 4 neutropenia, without fever. Gastrointestinal toxicity was moderate and peripheral neuropathy was mild, except for two patients who had concomitant pathologies or previous treatment, which might have caused some neuropathy. We concluded that paclitaxel given as a 3-hour infusion was easily administered for ambulatory treatment, with mild to moderate toxicity and promising results based on rate and duration of response as well as survival.
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PMID:Paclitaxel in platinum-resistant ovarian cancer patients. Argentine Multicenter Taxol Group. 934 23

The objectives of this study were to determine the toxicity and phase II dose of weekly paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) administration and to describe our initial experience with salvage weekly intravenous paclitaxel in women with advanced recurrent ovarian carcinoma. We conducted a phase I trial of paclitaxel administered as a 1-hour infusion in advanced ovarian cancer patients, using doses of 40 to 100 mg/m2/wk. As a follow-up study, we retrospectively reviewed the medical records of 45 patients with advanced, recurrent epithelial ovarian cancer treated between January 1, 1996, and October 30, 1996, with single-agent weekly intravenous paclitaxel (60 to 100 mg/m2, 1-hour infusions). Response for patients with measurable disease was based on improvements in physical examination or a greater than 50% reduction in the perpendicular diameters of all lesions in serial computed tomography. Since many of the patients did not have measurable disease, some evaluations of response to therapy were based on decline in serum carbohydrate antigen-125 according to published criteria. In our phase I study, 18 patients received 194 weekly courses of therapy at doses of 40, 50, 60, 80, and 100 mg/m2. The dose-limiting toxicity was defined as two or more patients with treatment delay or grade 3 toxicity (National Cancer Institute common toxicity criteria) at the same dose level. Treatment was delayed in two of three patients (for neutrophil counts < 1,500/microL at the 100 mg/m2 dose level); therefore, a phase II dose of 80 mg/m2/wk is recommended. No patient required hospitalization for neutropenia/fever. In the retrospective cohort review, the median patient age was 55 years (range, 32 to 79 years). All patients were heavily pretreated with multiple systemic chemotherapy regimens, including paclitaxel, with a median of four regimens (range, one to eight) before receiving weekly paclitaxel. Patients received a median of nine cycles of weekly paclitaxel (range, three to 37), with a median interval of 8 months (range, 1 to 32 months) between the last paclitaxel treatment and the institution of weekly therapy. Response was noted in 13 of 45 (28.9%) patients, with a median of seven treatments to achieve response. Chemotherapy was generally well tolerated, with treatments completed on a weekly schedule and only one hospitalization for nadir fever. We conclude that weekly intravenous paclitaxel is an active and well-tolerated regimen in heavily pretreated women with recurrent ovarian carcinoma. Prior therapy with paclitaxel does not preclude response to this regimen. A phase II trial of weekly paclitaxel in paclitaxel-refractory patients is under way.
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PMID:Salvage weekly paclitaxel in recurrent ovarian cancer. 934 25

Five promising new drugs for gynecological cancer were reviewed. Taxans (Paclitaxel: Taxol and Docetaxel: Taxotere) diterpenoid plant products enhance the polymerization of tublin. Taxol showed significant activity for platinum refractory ovarian cancer in a phase 1 clinical trial in the United States. The combination with cisplatin (CDDP) showed superior results to CDDP plus Cyclophosphamide and has been recognized as a new standard in adjuvant chemotherapy for advanced ovarian cancer. The major toxicities are myelosuppression, alopecia, and hypersensitivity reactions (HSRs). HSRs were overcome by pretreatment with anti-histamines and over 24 hours administration. It was also reported that Taxol was administered safely by over 3 hours infusion with reduced myelotoxicity, but the incidence of HSRs may be increased. Clinical trials of intraperitoneal administration and combination with Carboplatin (CBDCA) are ongoing. Taxotere, an analog of Taxol, is also effective as Taxol with a low incidence of HSRs. Topoisomerase inhibitors (Irinotecan hydrochloride: CPT-11 and Topotecan) have promising antitumor activity for ovarian and cervical cancer. CPT-11 is a semisynthetic camptothesin analog developed in Japan. It was also effective for platinum-resistant ovarian cancer, such as mucinous and clear cell carcinoma. An adverse effect was observed in the combination of CPT-11 and CDDP. The phase 1 clinical trial showed a 40% response rate against recurrent ovarian cancer. CPT-11 50-60 mg/m2 (day 1,8,15) and CDDP 50-60 mg/m2 (day 1) are a recommended schedule. The major toxicities are neutropenia and diarrhea. Thrombocytopenia is not severe and diarrhea is also controllable. Topotecan is also a promising topoisomerase inhibitor and reported superior result to Taxol for platinum refractory ovarian cancer. A phase II trial is ongoing for ovarian and cervical cancer in Japan. Nedaplatin, a new analog of cisplatin, has similar activity especially for cervical cancer with less myelotoxicity and nephrotoxicity.
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PMID:[Promising new drugs for gynecological cancer]. 935 Feb 38

CI-980 is a synthetic mitotic inhibitor that binds to the colchicine binding site of tubulin. It demonstrates broad activity against human and murine tumor models and shows no cross resistance with tumor models whose mechanism of resistance is mediated by P-glycoprotein (MDR-1). A phase I study was completed in 25 patients with solid tumors using a 24-hour infusion schedule, with courses repeated every 3 weeks. Eight dose levels were tested between 1.2 and 15.6 mg/m2. The maximum tolerated dose was 14.4 mg/m2. Neutropenia was dose-related but not dose-limiting; thrombocytopenia was infrequent. CNS toxicities were dose-limiting and consisted of dizziness, headache, loss of coordination, loss of consciousness, nervousness, and other symptoms. These events occurred near the end of the infusion and were reversible, usually within 24 hours. One patient who was to be treated at dose level 8 (intended dose was 19.2 mg/m2; actual dose was 15.6 mg/m2) became encephalopathic prior to completion of the infusion. Other adverse events included gastrointestinal toxicities (nausea, vomiting, anorexia, constipation, stomatitis, dyspepsia, bleeding, cheilitis), IV site erythema, fever, and fatigue. A partial response was observed in one patient with colon cancer and reductions in CA-125 levels were observed in 2 patients with ovarian cancer. Pharmacokinetics were linear and dose-proportional. Results indicate high systemic clearance and wide tissue distribution. Mean pharmacokinetic parameter values: T1/2 = 5.52 hours, plasma clearance 1163 mL/min/m2, and Vdss 376 L/m2.
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PMID:A phase I trial and pharmacokinetic evaluation of CI-980 in patients with advanced solid tumors. 938 46

Our objective was to determine the maximum tolerated dose (MTD) of paclitaxel when given as a 7 day continuous i.v. infusion, repeated every 3 weeks, and to evaluate the toxicity and the efficacy of such a schedule of administration as a salvage treatment in ovarian cancer patients pretreated and refractory to 3 or 24 h paclitaxel. Thirteen women were enrolled in this phase I trial. Four dose levels ranging from 105 to 157.5 mg/m2/cycle were explored. Two of four patients experienced dose-limiting febrile neutropenia at the dose of 157.5 mg/m2. No objective response was observed, although three patients experienced disease stabilization (five to six cycles), with regression of disease symptoms, two of them having sustained 50% or greater decrease in CA 125. We conclude that the MTD in this population was paclitaxel 140 mg/m2/7 days. Schedule-dependent mechanisms of resistance to paclitaxel could not be demonstrated in this clinical setting of heavily pretreated ovarian cancer patients.
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PMID:Schedule-dependent paclitaxel tolerance/activity: data from a 7 day infusion phase I study with pharmacokinetics in paclitaxel refractory ovarian cancer. 939 20

The efficacy and safety of docetaxel in clinical trials in patients with a variety of malignancies are reviewed. The overall response rate for docetaxel as a first-line treatment for metastatic breast cancer is 59%. Docetaxel in combination with doxorubicin or vinorelbine has proved particularly effective in the first-line treatment of metastatic breast cancer. Docetaxel is also one of the most active single agents in the treatment of non-small-cell lung cancer (NSCLC), producing an overall response rate of 27% when used as a first-line agent. Docetaxel plus cisplatin was more effective against NSCLC than either drug used alone, yielding response rates of 33-48%. Docetaxel has shown activity against a variety of other tumors, including ovarian cancer (response rate in second-line therapy, 34%), head-and-neck cancer (response rate in first-line therapy, 35%), and soft-tissue sarcoma (response rate in first-line therapy, 32%). The main toxic effect is grade 3-4 neutropenia, which occurs in 57% of treatment cycles but is brief and manageable. The dosage of docetaxel should be reduced from 100 mg/m2 to 75 mg/m2 if patients have neutropenia lasting more than one week, febrile neutropenia, or impaired liver function. Other adverse effects include severe fluid retention and asthenia. Some adverse effects can be avoided by administering corticosteroid premedication. Docetaxel has shown efficacy against a wide range of cancers in clinical trials and has a manageable adverse-effect profile.
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PMID:Efficacy and safety of docetaxel in clinical trials. 943 29

Docetaxel (Taxotere) has been studied at a dose of 100 mg/m2 i.v. as a one hour infusion every 3 weeks, in four phase II trials in patients with extensively pretreated ovarian cancer. A total of 340 patients were treated, including 256 patients in two separate EORTC (European Organization for Research and Treatment of Cancer) trials and 84 patients in two trials in the U.S.A. All patients had received prior cisplatin or carboplatin therapy and the treatment-free interval was less than 4 months in 155 patients. The overall response rate using conventional UICC criteria was 30% among 315 evaluable cases (95% confidence interval: 24-36%). Among 155 patients whose disease was most refractory (i.e. treatment-free interval was less than 4 months), the overall response rate was 28% (95% confidence interval: 19-36%). Response duration ranged from 4 to 17 months. Grade IV neutropenia was a common finding and fluid retention was observed. The incidence of febrile neutropenia ranged from 8 to 44% of patients with two deaths (i.e. 0.6% of the total treated) related to neutropenic sepsis. Docetaxel and paclitaxel (Taxol) have comparable activities in ovarian cancer. Ongoing studies with docetaxel include its use in patients as part of first-line therapy, as well as in patients refractory to paclitaxel. To prevent the development of fluid retention, these now involve the routine use of steroid prophylaxis. It is expected that docetaxel will prove to be an important addition to the drugs available for the treatment of ovarian cancer.
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PMID:Phase II trials of docetaxel (Taxotere) in advanced ovarian cancer--an updated overview. 947 Aug 2

Paclitaxel (Taxol) is a new class of anti-tumor agents which act by promoting the assembly and inhibiting the disassembly of microtubules. Single-agent studies have shown its significant activity for advanced cancers in various organs including ovary, lung, breast, and head and neck. Combination therapies with other anticancer agents have been extensively investigated in these cancers. Paclitaxel combined with cisplatin is now considered to be the standard treatment for advanced ovarian cancer. In other cancers, promising results have been obtained in several studies of paclitaxel-based chemotherapy. Major toxicities of paclitaxel-monotherapy are hypersensitivity reaction, neutropenia, and peripheral neuropathy. Combination of other cytotoxic agents sometimes leads to severer toxicities such as neurotoxicity with cisplatin and cardiotoxicity with anthracycline. Although further evaluation is needed, paclitaxel will be a main agent in the treatment of advanced solid tumors.
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PMID:[Paclitaxel (taxol): a review of its antitumor activity and toxicity in clinical studies]. 953 Mar 72

A phase II trial was conducted in order to assess the efficacy and toxicity of paclitaxel given at a dose of 175 mg/m2 in a 3-hour infusion every 3 weeks in patients with recurrent or cisplatin (CDDP) carboplatin-refractory ovarian cancer. Forty-two patients with a median age of 61 years (range 34-76 years) entered the study. Most patients had bulky disease. Thirty-three patients (78.5 %) presented with stage III and IV diseases. Twenty-two patients (52.3%) had previously been treated with only 1 regimen and 20 patients (47.7%) with > or = 2 regimens. The median treatment interval from the last previous therapy was 4.5 months (range 2-26 months). From 41 patients evaluable for response, 3 (7.3%) achieved a complete and 4 (9.8%) a partial response. All 3 complete and 2 out of the 4 partial responders had previously received > or = 2 chemotherapeutic regimens. Grade 3-4 toxicities included granulocytopenia (35%), which was of short duration, neurotoxicity (9.75%) and alopecia (60.9%). Two patients with grade 4 neutropenia were hospitalized due to pneumonia, which was successfully treated by broad-spectrum antibiotics and administration of G-CSF. A severe hypersensitivity reaction occurred in 1 patient early during the first cycle, resulting in discontinuation of treatment. Median relapse-free survival was 6.9 months, median time to progression 6.2 months and median survival 13.2 months. In conclusion, paclitaxel given at a dose of 175 mg/m2 as a 3-hour infusion every 3 weeks appears to be an efficacious and well-tolerated treatment in patients with recurrent or CDDP/carboplatin-refractory ovarian cancer.
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PMID:Paclitaxel in cisplatin or carboplatin-pretreated ovarian cancer. Phase II study. 956 55

We have conducted an open, controlled study on the febrile neutropenia effects by Lenograstim (Granocyte) therapy following cytotoxic chemotherapy of cisplatinum and cyclophosphamide in patients with primary advanced epithelial ovarian cancer. Eligible patients (n = 17) were divided into 2 groups receiving a combined chemotherapy of intravenous cisplatinum (70 mg/m2) and cyclophosphamide (700 mg/m2) with or without the addition of Lenograstim. Subcutaneous administration of Lenograstim (100 micrograms/day) for 7 consecutive days was given from day 8 to day 14 of the 3rd to the 5th cycle of chemotherapy in Lenograstim treated patients. After 3 cycles of treatment, Lenograstim treated patients (group 1, n = 10) showed a significant improvement in white blood cell (WBC) count as compared with group 2 (control) of 7 patients (p = 0.00002). Group 1 patients also showed an increased C-reactive protein, though of no significance. There were no significant differences among the 2 groups regarding ESR, hematocrit, platelet counts and blood chemistry profiles. This preliminary data encourages more study of the benefits of Lenograstim in the treatment of ovarian cancer.
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PMID:The use of lenograstim (Granocyte) in chemotherapy for ovarian cancer. 968 Nov 28


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