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)

Thirty-two patients with advanced breast cancer have been treated with epirubicin 90 mg/m2, immediately followed by paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) infused over 3 hours, every 21 days. The starting paclitaxel dose was 135 mg/m2, increased in subsequent triplets of patients until the maximum tolerated dose was reached at 200 mg/m2. One hundred seventy-six courses have been administered; dose-related grade 4 neutropenia was observed in 66% of the courses, with 12 episodes of febrile neutropenia. Two patients showed a decline of left ventricular ejection fraction below 50% after six courses, but no signs of congestive heart failure have been reported. The response rate is 76% (95% confidence interval, 56% to 90%), with 14% complete remissions. This level of activity is encouraging considering that 84% of the patients had failed adjuvant chemotherapy (with anthracyclines in 14 cases), and 19 had progressive disease following hormone therapy for metastasis. In another study, the toxicity and activity of a salvage regimen consisting of paclitaxel 135 mg/m2 over 3 hours plus vinorelbine 25 mg/m2 in an intravenous bolus on day 1 were evaluated; vinorelbine was given again on day 8 (in 14 patients) or on day 3 (in 20 patients), and the courses were repeated every 3 weeks. Thirty-four previously treated patients with advanced breast cancer entered the study; 20 had received one prior line of chemotherapy, II had two lines, and three patients had three lines. Thirty-two patients had been exposed to anthracyclines. Grade 4 neutropenia was observed in 64% of the courses, with 13 episodes of febrile neutropenia; four episodes of grade 3 mucositis have been reported with vinorelbine days 1 and 3. A delay in the administration of chemotherapy was necessary in 17% of the courses with vinorelbine days 1 and 8 and 16% of the courses with vinorelbine days 1 and 3; moreover, the vinorelbine dose was reduced or the drug omitted on day 8 in 86% of the courses and on day 3 in 16% of the course. An objective response was achieved in 43% of the patients. In conclusion, the combination of paclitaxel plus vinorelbine is an active salvage regimen and can be administered at greater dose intensity with the day 1 and 3 schedule.
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PMID:Paclitaxel combinations as front-line and salvage chemotherapy regimens in advanced breast cancer. 899 97

This phase I study investigated the maximum tolerated dose of cisplatin, etoposide, and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in 18 patients with advanced small cell lung cancer. Cisplatin (80 mg/m2) and etoposide (50 or 80 mg/m2 intravenously and 100 or 160 mg/m2 orally) were infused concomitantly 30 minutes after a 3-hour infusion of paclitaxel (135, 175, or 200 mg/m2). This order of administration was known to cause less toxicity than the reverse order. Granulocyte colony-stimulating factor was given as necessary. Overall, complete responses were observed in 33% of evaluable patients and partial responses were seen in 67%. No patient progressed during therapy. Median survival exceeded 12 months, with 53% of patients alive at 1 year. Untreated patients in similar health survive approximately 6 to 16 weeks. Hematologic toxicities were seen most frequently, and neutropenia was seen most often and was the most severe. Febrile neutropenia occurred in one patient; grade 4 thrombocytopenia did not occur at all. Nonhematologic toxicity was mild. Nausea and vomiting generally were well controlled, and there were no instances of severe allergic reaction. Although the maximum tolerated dose has not yet been defined, one of two patients in the group receiving the highest doses encountered a dose-limiting toxicity. Thus, we expect to recommend the following dosages for further study: cisplatin 80 mg/m2, etoposide 80 mg/m2, and paclitaxel 175 mg/m2. All patients had an objective response and one third had a complete response, compared with 10% of patients in most series. We conclude that paclitaxel can be added safely to full doses of cisplatin and etoposide with encouraging efficacy, and recommend a randomized trial be undertaken to compare the two-drug regimen with the three-drug regimen.
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PMID:Phase I study of cisplatin, etoposide, and paclitaxel in patients with extensive-stage small cell lung cancer: a University of Colorado Cancer Center study. 900 14

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is a new cytotoxic chemotherapeutic agent with a novel mechanism of action. Single-agent paclitaxel studies have shown promising activity in both small cell and non-small cell lung cancers. In non-small cell lung cancer, response rates of 22% to 26% and 1-year survival rates of 40% were reported with both 3-hour and 24-hour infusions of paclitaxel. In small cell lung cancer, 24-hour infusions produced response rates of 61%. These data indicate that paclitaxel is one of the most active agents for all lung cancer patients. Combination studies demonstrated that paclitaxel could be combined with either cisplatin or carboplatin at full doses using either a 3-hour or a 24-hour infusion schedule. Response rates with these combinations have been high, usually 40% to 50%, which are higher than with any of the drugs used alone. Neutropenia is the most frequent toxicity and occurs less frequently with the 3-hour infusion. Thrombocytopenia occurred less frequently than expected. One completed randomized study showed that the paclitaxel/cisplatin regimen was superior to the etoposide/cisplatin regimen with respect to response rate and survival. Additional randomized studies are necessary to determine whether the combinations are superior to single-agent paclitaxel, to define the optimal dose with the 3-hour infusion schedule, to define the optimal schedule (3 hours v 24 hours), and to determine whether paclitaxel can be combined with other new agents.
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PMID:The North American experience with paclitaxel combined with cisplatin or carboplatin in lung cancer. 900 16

In preparation for the design of phase II studies in lung cancer, low-dose carboplatin, fixed at a target area under the concentration-time curve (AUC) of 4.0 or 4.5 mg x min/mL, has been combined with escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in a series of studies to establish the maximum tolerated dose of the combination. In patients who had received prior chemotherapy, the maximum tolerated paclitaxel dose was 135 mg/m2 (carboplatin target AUC 4.0); the dose-limiting toxicity was febrile neutropenia. Without granulocyte colony-stimulating factor support in chemotherapy-naive patients (carboplatin target AUC 4.5), and with granulocyte colony-stimulating factor in chemotherapy-pretreated patients, the current paclitaxel dose is 290 mg/m2. The maximum tolerated dose has not been defined. In a study in which paclitaxel was given by 1-hour infusion with carboplatin (target AUC 4.5), a 205 mg/m2 dose was poorly tolerated. No evidence of pharmacokinetic interactions between paclitaxel and carboplatin was found. Twenty-one evaluable patients with lung cancer have been treated to date. There have been two partial responses, one minor response, and 10 patients with stable disease at paclitaxel doses of 100 to 270 mg/m2.
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PMID:Early phase studies with paclitaxel/low-dose carboplatin in patients with solid tumors. 900 17

Few cytotoxic agents tested in adequate phase II trials involving patients with non-small cell lung cancer have produced single-agent response rates greater than 15%. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is one of them, with reported response rates ranging from 21% to 36%. Platinum-based regimens have been key to the development of the most effective combination therapies for NSCLC. We are currently investigating the efficacy and toxicity of combining paclitaxel (175 mg/m2) given by 3-hour infusion, followed by cisplatin (75 mg/m2) via 1-hour infusion, on a 21-day schedule for the treatment of 75 chemotherapy-naive patients with stage IIIB (17.3%) or stage IV (82.6%) non-small cell lung cancer. Patient characteristics include a median age of 58 years (age range, 28 to 75 years) and a median Eastern Cooperative Oncology Group performance status of 2; 19 patients (25.3%) are women and 56 (74.7%) are men. All patients received standard prophylactic premedication as well as adequate hydration. To date, 75 subjects and 328 courses are evaluable for toxicity. Hematologic toxicities have been moderate; grade 3 or 4 neutropenia occurred in 37% of cycles (50% of patients), and grade 3 or 4 thrombocytopenia was observed in only 2% of cycles (2% of patients). Other notable toxicities were World Health Organization grade 2 or 3 alopecia and nausea/vomiting. Grade 1 or 2 peripheral neuropathy occurred in 26% and grade 3 or 4 in only 1% of all courses. Of 67 patients evaluable for response, complete remission was noted in three (5%) patients, partial remission in 25 (37%) patients, stable disease in 22 (33%) patients, and progressive disease in 17 (25%) patients. These results suggest that combination paclitaxel/cisplatin is active and well tolerated in the treatment of non-small cell lung cancer.
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PMID:Phase II study of paclitaxel and cisplatin in patients with non-small cell lung cancer. 900 21

During previous phase I experience of weekly paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) used as a radiation sensitizer, decreased hematologic toxicity was noted. Therefore, an extended phase I/II trial of weekly paclitaxel in patients with chemotherapy-naive, metastatic non-small cell lung cancer was conducted to determine the maximum tolerated dose and activity of this alternative schedule. Twenty-six patients entered this study through six dose levels of paclitaxel (100, 125, 135, 150, 175, and 200 mg/m2/wk) administered weekly for 6 of 8 weeks. Doses were escalated if more than 80% of the intended dose was administered in the preceding cohort without evidence of grade 3 nonhematologic toxicity. All patients had a performance status of 0 to 2 and a median age of 63 years. Sites of disease included the lung, bone, liver, soft tissue, and brain. Twenty-four patients completed the first 8-week cycle and are evaluable for toxicity and response. Dose-limiting toxicity occurred at 200 mg/m2/wk and consisted primarily of neutropenia. Only one evaluable patient required hospitalization for febrile neutropenia. Other toxicities included rash, pulmonary infiltrate, myalgia, neuropathy, and alopecia. Nine of 24 patients (38%) demonstrated objective responses. We conclude that the maximum tolerated dose of weekly paclitaxel administered for 6 weeks in an 8-week cycle is 175 mg/m2/wk. The response rate is encouraging and this schedule merits further investigation.
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PMID:Phase I/II trial of weekly paclitaxel in patients with advanced lung cancer. 900 23

Based on the activity of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and the significant 1-year survival rates of patients with non-small cell lung cancer treated with carboplatin, the Hellenic Cooperative Oncology Group initiated a phase II trial using both agents in patients with inoperable stage III or IV disease to investigate the efficacy and toxicity of the combination. Since July 1995, 31 patients fulfilling all eligibility criteria entered this study. All patients received paclitaxel 175 mg/m2 as a 3-hour infusion and carboplatin dosed to an area under the concentration-time curve of 7, every 3 weeks. No granulocyte colony-stimulating factor was given. Among the 29 male and two female patients, the median age was 55 years (age range, 29 to 73 years) and the median Eastern Cooperative Oncology Group performance status was 1. Most of the patients had stage IV adenocarcinoma (19) with low differentiation (15). The median number of chemotherapy cycles was two, with a range of one to six. Among 21 patients evaluable, seven achieved a partial response, 10 had stable disease, and four had progressive disease. It is too early to evaluate nine patients. Grade 2/3 nonhematologic toxicity included alopecia (48%), neurotoxicity (3.7%), and myalgia/arthralgia (7.4%). Grade 2/3 neutropenia occurred in 11.1% of patients, whereas grade 2 thrombocytopenia was seen in only 3.7%. One patient died following complications of severe allergic reaction. In conclusion, although this study is ongoing, combination treatment using paclitaxel and carboplatin is both effective and well tolerated in patients with inoperable non-small cell lung cancer.
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PMID:Paclitaxel and carboplatin in inoperable non-small cell lung cancer. 900 26

This ongoing phase I study sought to establish the maximum tolerated dose of the combination of carboplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given without routine growth factor support to previously untreated patients with stage IIIB and IV non-small cell lung cancer. Paclitaxel was administered as a 3-hour intravenous infusion. The carboplatin infusion was administered over 30 minutes immediately afterward. Patients were assigned sequentially to one of eight treatment groups in which paclitaxel and carboplatin were administered in doses ranging from 130 to 185 mg/m2 and from 230 to 350 mg/m2, respectively. Twenty-four patients have been treated to date, and the maximum tolerated dose has been reached at paclitaxel 185 mg/m2 and carboplatin 350 mg/m2. The combination has an excellent safety profile, with only a few, short-lasting episodes of neutropenia observed and no evidence of infection. At the doses tested, thrombocytopenia has not occurred.
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PMID:Preliminary results of a dose-finding study of paclitaxel and carboplatin in patients with advanced non-small cell lung cancer. 900 29

This phase I dose-escalation study was undertaken to determine the maximum tolerated doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and ifosfamide that could be administered without growth factors to previously untreated patients with non-small cell lung cancer. Forty patients with advanced non-small cell lung cancer were treated with a 3-hour infusion of paclitaxel and a 1-hour infusion of ifosfamide, repeated every 3 weeks. Groups of three patients each entered at escalating dose levels in a traditional phase I design. Starting doses were paclitaxel 100 mg/m2 and ifosfamide 3 g/m2; all patients received premedication with dexamethasone and diphenhydramine, and some also received a 5-HT3 blocker. Dose escalation was permitted only after full toxicity assessment had been completed for two cycles for all patients at a dose level. Dose escalation of paclitaxel continued to 225 mg/m2 without dose-limiting toxicity, but further escalation was not attempted because of the known likelihood of neurotoxicity above this dosage. Instead, ifosfamide was increased to 4 g/m2 for the final dose level. At these doses, dose-limiting myelosuppression was not seen, and there was only one episode of febrile neutropenia in 162 treatment cycles. Drug-related ifosfamide toxicities included gross hematuria and confusion in one patient each; paclitaxel-related symptoms included flu-like syndrome in most patients, arthralgia and/or myalgia in eight and 25 patients, respectively, and paresthesia in 14 patients. Despite premedication, 15 patients experienced grade 1 hypersensitivity reactions. Partial response was seen in 21% of patients (confidence interval, 9.3% to 36.5%), and the median duration of response was 5.9+ months (range, 3 to 14 months). The median survival was 9.1 months (range, 1 to 12 months). In summary, outpatient paclitaxel given over 3 hours and single-dose ifosfamide given over 1 hour may be combined safely without hematopoietic growth factors for the treatment of patients with non-small cell lung cancer. The recommended doses for phase II study are paclitaxel 225 mg/m2 and ifosfamide 4 g/m2, every 3 weeks.
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PMID:Phase I dose-escalation trial of paclitaxel and ifosfamide in patients with advanced non-small cell lung cancer. 900 30

Based on superior results observed with combined-modality therapy over radiotherapy alone and on the authors' previous work with carboplatin and standard daily thoracic radiotherapy in patients with advanced, unresectable non-small cell lung cancer, a phase II study was designed to incorporate radiosensitizing doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) into the carboplatin/radiotherapy regimen, to improve the therapeutic index and define the toxicities. Thirty-two patients have been entered. Paclitaxel 45 mg/m2/wk was administered over 3 hours prior to carboplatin (100 mg/m2/wk) and thoracic radiotherapy (1.8 Gy/d 5 days a week; total dose, 60 to 65 Gy). No grade 4 toxicities occurred. Seven patients had chemotherapy doses delayed because of grade 3 neutropenia, and one patient had grade 3 mucositis/esophagitis that required hospitalization. Median survival has not yet been reached, and all patients are being followed. These preliminary data demonstrate the feasibility of combined concurrent chemoradiotherapy, with acceptable toxicities. Further investigation is needed to optimize carboplatin dosage with adaptive control using formulas based on pharmacokinetics and pharmacodynamics. Full-dose induction chemotherapy regimens to maximize the systemic effects of chemotherapy should precede concurrent chemoradiotherapy in future studies.
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PMID:Chemoradiotherapy in non-small cell lung cancer: paclitaxel/carboplatin/radiotherapy in regionally advanced disease. 900 36


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