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)

Two phase II breast cancer studies have been completed with gemcitabine in patients with locally advanced or metastatic breast cancer. Gemcitabine was administered as a 30 minute intravenous infusion on days 1, 8, and 15 of a 28-day cycle. In a European study of 44 patients, 40 patients were evaluable for response, 26 having received chemotherapy (seven in the adjuvant setting). The mean number of completed cycles administered was 2.7 and 81% of doses were delivered as scheduled. There were three complete responses and seven partial responses, giving an overall response rate of 25.0% (95% confidence interval, 12.7% to 41.2%). Four patients were not evaluable for efficacy: one had insufficient therapy, two had no bidimensionally measurable disease, and one had insufficient therapy and no bidimensionally measurable disease. The median duration of survival was 11.5 months. Hematologic toxicity was generally mild, with World Health Organization grade 3 and 4 leukopenia occurring in 6.8% and 2.3% of patients and neutropenia in 23.0% and 7.0% of patients, respectively. Nonhematologic toxicity was minimal. Flu-like symptoms were mild and transient. Only one patient developed alopecia. In a US study, 18 of 21 heavily pretreated patients were evaluable, all of whom had stage IV disease. The median number of cycles administered was two, with 12% of injections omitted and 31% reduced by 50%. No responses were observed in this smaller study. The safety profile was similar to that in the European study, although myelosuppression was greater in the US study, in which patients were heavily pretreated. The differing results observed from single-agent studies of gemcitabine in advanced breast cancer may be explained in part by the amount of prior chemotherapy received and the lower mean dose of chemotherapy administered in the US study. Responses have been observed in both chemotherapy-naive and previously treated patients. The drug was extremely well tolerated in both studies, even in heavily pretreated patients. In view of its modest toxicity profile and its novel mechanism of action, gemcitabine deserves further evaluation in breast cancer patients and, in particular, because of its relative lack of myelotoxicity would be an ideal candidate for combination chemotherapy.
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PMID:Phase II activity of gemcitabine in advanced breast cancer. 889 87

No effective second-line therapy has been developed for patients with metastatic colorectal cancer progressive after than fluorouracil(FU)-containing chemotherapy. Encouraging results have been reported with weekly 24-hour FU infusion. The aim of this study was to test the activity of weekly FU infusion plus modulation with methotrexate and L-leucovorin in pretreated colorectal cancer patients. Seventeen patients with metastatic colorectal carcinoma were treated with methotrexate (40 mg/m2 on day 1), L-leucovorin (100 mg/m2 as a 4-hour infusion on day 2), and FU (2,600 mg/m2 as a 24-hour infusion on day 2). All patients had measurable disease and a performance status of ECOG O-2. Two of the 17 evaluable patients achieved partial remission (12%; 95% confidence interval 2-24%), 9 had stable disease, and 6 progressive disease. Median time to progression was 4 months (range, 2-8) and median survival was 7 months (range, 3-12+). Toxicity was generally mild or moderate and consisted of mucositis, diarrhea and neutropenia. Pretreated patients with metastatic colorectal, carcinoma benefit only marginally from this treatment schedule.
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PMID:Double modulation with methotrexate and L-leucovorin of weekly 24- hour fluorouracil infusion in fluorouracil-refractory colorectal cancer. 892 Jul 75

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

Tallimustine binds to the minor groove of DNA where it alkylates the N3 position of adenine and may interfere with gene transcription. We conducted a phase II trial of Tallimustine given at a dose of 750 micrograms/m2 intravenously every 4 weeks in patients with small cell lung cancer progressing or relapsing following cisplatin or carboplatin-based chemotherapy. We treated 14 eligible patients with a performance status 0, 1 or 2, bi-dimensionally measurable disease and adequate end-organ function. The main toxicity was neutropenia with a median granulocyte count of 0.1 x 10(9) per liter (range 0-3.9) and four patients (27%) developing febrile neutropenia. In addition, most patients (93%) experienced lethargy. No objective responses were seen. A mixed response was seen in one patient and three others had stable disease for a median of 3.7 months. We conclude that Tallimustine is an ineffective agent in previously treated small cell lung cancer.
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PMID:Tallimustine is inactive in patients with previously treated small cell lung cancer. A phase II trial of the National Cancer Institute of Canada Clinical Trials Group. 895 81

Our phase II study results demonstrating high efficacy and low toxicity for a weekly schedule of high-dose, 24-hour infusional 5-fluorouracil(5-FU)/folinic acid (HD5-FU/FA) in intensively pretreated patients with metastatic breast cancer prompted addition of paclitaxel (Taxol) to the regimen, for a phase I/II study of outpatient second-line treatment of metastatic breast cancer. That study further prompted the addition of cisplatin (Platinol) to the regimen for first-line treatment. So far, 28 patients with metastatic breast cancer have been evaluated. Pretreatment comprised adjuvant chemotherapy in 24 of 28 patients, but no prior chemotherapy for metastatic disease. Patients were treated with HD5-FU 2 g/m2 (24-hour infusion) plus FA 500 mg/m2 (2-hour infusion prior to FU) weekly for 6 weeks (days 1, 8, 15, 22, 29, and 36); in addition, paclitaxel 175 mg/m2 (3-hour infusion) was administered on days 0 and 21 and cisplatin 50 mg/m2 (1-hour infusion) on days 1 and 22 prior to HD5-FU/FA, repeated every 50 days. Patients were treated as outpatients using Port-a-Cath systems and portable pumps. Neutropenia was common (67% World Health Organization grade 3) but mild to moderate in most patients and was of short duration. No hospitalizations were required because of febrile neutropenia, and no granulocyte colony-stimulating factor support was used. Aside from common total alopecia, nonhematologic toxicities consisted mainly of moderate myalgia, diarrhea, mucositis, and nausea and vomiting. Hand-foot syndrome and peripheral neuropathy were cumulative and occurred most commonly during the third treatment cycle, with mild-to-moderate expression. In 28 patients with bidimensionally measurable disease, 25% (7/28) attained a complete response, 57% (16/28) achieved partial response, 11% (3/28) had stable disease, and 7% (2/28) had disease progression. Overall response was 82% (95% confidence interval, 66% to 100%). Eight of 28 patients are still receiving treatment. It is concluded that the combination of paclitaxel/cisplatin with weekly HD5-FU/FA appears to be effective in the first-line treatment of metastatic breast cancer. Preliminary results must be confirmed by the final analysis of response duration, time to progression, and survival.
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PMID:Infusional 5-FU, folinic acid, paclitaxel, and cisplatin for metastatic breast cancer. 914 90

An extended phase II study was performed to evaluate single-agent paclitaxel as salvage chemotherapy for ovarian cancer. The aim of this study was to evaluate the 3-h infusion schedule of paclitaxel in terms of toxicity and antitumour efficacy. Furthermore, we analysed the impact on response and survival of the extent of prior chemotherapy and status of resistance against platinum. This study was an open, non-randomised, multicentre trial. The dose of paclitaxel used was 175 mg/m2 in patients who had received one or two prior therapies, and 135 mg/m2 in patients who had received three prior therapies. Paclitaxel was given as a 3-h infusion. Courses were repeated every 3 weeks. 114 patients with platinum-pretreated epithelial ovarian cancer were recruited of whom 112 were found eligible and evaluable for toxicity. 104 patients with bidimensionally measurable disease who received more than one course of chemotherapy were evaluable for response, progression-free (PFS) and survival. Toxicity was generally manageable. Main toxicities were non-cumulative neutropenia with 22.3% of courses with WHO grade 3/4 and peripheral neuropathy which occurred in more than half of the courses and was of WHO grade 2 and 3 in 20.1 and 1.3% of the courses, respectively. Neuropathy was associated with the higher dose per course and with cumulative paclitaxel dose. Objective responses were reported in 20% (21/104) of the patients (95% CI 13-29%) with a median response duration of 36.7 weeks. Survival and PFS for the whole group were 45.9 and 15.1 weeks, respectively. Performance status, number of tumour lesions and extent of prior chemotherapy were found to be prognostic factors for survival. Extent of prior chemotherapy was the only prognostic factor for PFS. Platinum resistance did not predict response to treatment. Paclitaxel 175 mg/m2 given as a 3-h infusion is an appropriate treatment for patients with platinum-resistant ovarian cancer who have not previously received more than two chemotherapy regimens. Paclitaxel did not show results superior to historical data for platinum retreatment in patients with platinum-sensitive, recurrent ovarian cancer.
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PMID:Extended phase II study of paclitaxel as a 3-h infusion in patients with ovarian cancer previously treated with plantinum. 915 20

This study evaluated the efficacy and safety of topotecan, a topoisomerase I inhibitor, in patients with advanced squamous cell cancer of the head and neck. Topotecan was administered intravenously (over 30 min) daily for 5 days every 3 weeks at a starting dose of 1.5 mg/m2/day. Eligibility required no prior chemotherapy, measurable disease, and performance status of < or = 2. Quality of life (QOL) assessment was performed at specified time points using the Spitzer QOL index and the symptom distress scale. Of 26 patients entered into the study, 23 and 22 patients were assessable for toxicity and response, respectively. One complete and two partial responses were observed, with response durations of 9, 4, and 1.5 months, respectively. Six patients had stable disease, including one patient with a 45% tumor shrinkage. The median survival for all patients entered was 4 months. Neutropenia was the major dose-limiting side effect, with grade 4 toxicity observed in 42% of all cycles of treatment. Grade 3 anemia occurred in 16% of all cycles, and nine patients required blood transfusions. Nonhematologic toxicities were infrequent and mild to moderate. QOL assessment revealed no significant change of total scores between each assessment point. Topotecan is a well-tolerated new agent with similar single-agent activity to that of cisplatin, 5-fluorouracil, and methotrexate in advanced head and neck cancer. Further investigation of this agent with other chemotherapeutic drugs and with concurrent radiation therapy is appropriate.
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PMID:A phase II study of topotecan in patients with recurrent head and neck cancer. Identification of an active new agent. 916 58

Hormone-refractory prostate cancer is characterized by a low response rate following second-line therapy. Encouraging results have been reported in Phase II studies with estramustine associated with vinblastine or etoposide. Vinorelbine is a new semisynthetic vinca alkaloid that has demonstrated activity in prostate cancer. We therefore evaluated the activity of the following schedule: estramustine, 400 mg/m2 orally days 1-42; etoposide, 50 mg/m2 orally days 1-14; and 28-42; vinorelbine, 20 mg/m2 days 1, 8, 28, and 35; cycles being repeated every 8 weeks. Twenty-five patients have been included and are assessable for response and side effects. Patient characteristics were as follows: median age, 71 years (range 55-81); ECOG performance status 0-2; nonosseous disease, 3 cases; bone metastases, 23 cases. Sixty-two cycles have been delivered. Two patients with measurable disease and six patients with bone disease had a partial remission for an overall response rate of 32% (95% confidence interval 15-53%). Seven patients had stabilization of disease and 10 had progression of disease. Median duration of response was 3 months (range 2-5). Prostate-specific antigen in 14 patients (56%) decreased from baseline by at least 50%. Toxicity was manageable. Neutropenia was mild, with only three cases of grade III-IV toxicity. Two patients had severe anemia. The results of this study indicate that the schedule is active and well tolerated in hormone-refractory prostate cancer patients.
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PMID:Phase II study of estramustine, oral etoposide, and vinorelbine in hormone-refractory prostate cancer. 925 95

This study was performed to determine the activity and toxicity of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given by 1-hour infusion plus carboplatin in the treatment of patients with advanced non-small cell lung cancer when used in a multicenter, community-based setting. The study population included 100 chemotherapy-naive patientswith stage IIIB or IV non-small cell lung cancer, Karnofsky performance status 70 to 100, measurable disease, and adequate kidney, liver, and bone marrow function. All patients received paclitaxel 225 mg/m2 intravenously by 1-hour infusion followed immediately by carboplatin at a targeted area under the concentration-time curve of 6.0 (Calvert formula). Cycles were repeated every 21 days. Colony-stimulating factors were not used routinely. Thirty-eight (38%) of 100 patients had objective responses (38 [40%] of 94 evaluable patients) to treatment (three complete responses, 35 partial responses). Thirty-two other patients had stable disease at initial re-evaluation. Weight gain during treatment occurred in 47% of those patients with objective response or stable disease. The median survival among all 100 patients was 8 months, with a 1-year survival rate of 42%. Leukopenia was common, but hospitalization for treatment of neutropenia and fever occurred in only 3% of courses. Cumulative peripheral neuropathy occurred consistently, but usually after the third or fourth course; it was severe (grade 3) in only 15% of patients. Other grade 3 and 4 toxicity was uncommon. One patient died as a result of treatment due to sepsis. This large, multicenter, community-based phase II trial demonstrates the efficacy of paclitaxel/carboplatin combination chemotherapy in advanced non-small cell lung cancer. This regimen is relatively well tolerated and when paclitaxel is given by 1-hour infusion, this treatment is easily administered in the outpatient setting.
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PMID:Paclitaxel (1-hour infusion) plus carboplatin in the treatment of advanced non-small cell lung cancer: results of a multicenter phase II trial. 933 Nov 13

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


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