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)

We conducted a multi-institutional (11 facilities), early phase II study of BMS-181339 (paclitaxel), a novel anti-cancer drug, for non-small cell lung cancer (NSCLC). The 150 mg/m2 dose of paclitaxel was given by intravenous infusion over 24 hours every three weeks. When fifteen patients were accumulated, the interim review revealed that three of 15 eligible patients had a partial response for a response rate of 20%. The most common toxic effects were grade 3 or 4 leukopenia seen in 73.3% (11/15), and grade 4 neutropenia in 93.3% (14/15). One patient with neutropenia had suspected septic shock, which could be managed by G-CSF and antibiotics. No serious hypersensitivity reaction was seen with premedication of anti-allergic drugs, although mild allergic reactions such as skin rash and flush, were observed in 20.0% (3/15). Other adverse reactions, including alopecia, fever, arthralgia, myalgia and peripheral neuropathy, were mild in most cases. We conclude that it is relevant to proceed to a late phase II study for NSCLC.
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PMID:[Early phase II study of BMS-181339 (paclitaxel) in patients with non-small cell lung cancer. BMS-181339 Non-Small Cell Lung Cancer Study Group]. 864 20

Vinorelbine tartrate (Navelbine, Burroughs Wellcome Company, Research Park, NC) is a semisynthetic analog of vinblastine that has been approved by the Food and Drug Administration for use in the treatment of advanced, unresectable non-small cell lung cancer. It has a favorable safety profile and can safely and easily be administered in the outpatient setting on a weekly basis. The major toxicity is severe, granulocytopenia (absolute neutrophil count < 500 cells/mm3), that occurs in approximately 40% of treated patients. This granulocytopenia is rapidly reversible, and does not increase in severity with subsequent cycles. Despite the high incidence of granulocytopenia, only about 8% of patients require hospitalization for the treatment of febrile neutropenia. This article also reviews information concerning the incidence and management of the other major side effects including constipation, paresthesias, decreased deep tendon reflexes, myalgia, and injection site reactions. Guidelines for the safe administration of this agent along with suggestions for patient education are also presented. The potential significance of the impact that this new agent may have in the treatment of advanced, unresectable non-small cell lung cancer and advanced breast cancer is stressed.
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PMID:Vinorelbine tartrate: a promising new chemotherapeutic agent. 870 38

A phase II study of Paclitaxel in patients with ovarian cancer by 3-hour intravenous infusion was undertaken by a cooperative study group of 30 institutes. Of 66 cases enrolled, 57 cases were evaluable for efficacy, and 63 cases were evaluable for safety. In spite of the fact that all cases for efficacy evaluation were previously treated with chemotherapy including platinum-based drugs, 2 cases of complete response (CR) and 15 cases of partial response (PR) were observed, with a response rate of 29.8% (The 95% confidence interval of response rate was 18.4-43.4%). Paclitaxel also showed 28.2% (11/39) response rate in patients refractory to treatment by platinum-based drugs. Histologically, the response rates were 28.9% (11/38) in serous adenocarcinoma, 40.0% (2/5) in clear cell adenocarcinoma and 25.0% (1/4) in mucinous adenocarcinoma. As the major laboratory abnormalities, leukopenia, neutropenia and decrease in hemoglobin were observed with incidence rates of 98.4% (62/63), 95.2% (59/62) and 85.7% (54/63), respectively. However, these abnormalities were clinically manageable by either withdrawal of medication, administration of antibiotics, G-CSF or metachysis etc. In addition, thrombocytopenia, elevation in GOT and GPT were seen with moderate incidence. Peripheral neuropathy was a major adverse symptom with an incidence of 79.4% (50/63), followed by alopecia, myalgia, arthralgia and fever. However, the majority of these adverse reactions were less than grade 3. From these findings, we confirmed that 3-hour intravenous infusion of Paclitaxel was a clinically useful chemotherapeutic agent in patients with ovarian cancer.
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PMID:[Phase II study of paclitaxel (BMS-181339) in patients with ovarian cancer by 3-hour intravenous infusion]. 871 25

Based on preclinical data, we designed a phase I/II clinical trial to determine the efficacy and toxicity of doxorubicin followed by paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the treatment of patients with advanced breast cancer (either untreated or relapsed after adjuvant therapy). In the phase I study, 19 enrolled patients received bolus doxorubicin (50 mg/m2) and, after a 16-hour interval, escalating doses of paclitaxel (from 130 to 250 mg/m2 in 30-mg/ m2 increments) by 3-hour infusion every 3 weeks for a maximum of eight cycles. Paclitaxel doses were increased if the maximum tolerated dose (MTD; defined by dose-limiting toxicities) had not been reached. Analysis of the 128 cycles assessable for toxicity demonstrated neutropenia (< 500/microL) in 20% of cycles with no significant clinical events. No relevant clinical cardiotoxicity was observed. Other toxicities included mild peripheral neuropathy and mild myalgia/arthralgia (In 37.5% and 30.4% of cycles, respectively). The maximum tolerated paclitaxel dose was not reached at the 250 mg/m2 dose level. In the second phase, 13 patients were treated with fixed doses of both drugs (doxorubicin 50 mg/m2 and paclitaxel 220 mg/m2, the dose level immediately preceding the highest paclitaxel dose used in phase I). Grade 4 neutropenia occurred in 36 of the 87 cycles but was complicated by fever in only eight cycles (9%); three patients needed granulocyte colony-stimulating factor. Peripheral neuropathy (grades 1 and 2 in 41.3% and 5.7% of cycles, respectively) and a myalgic syndrome (grades 1 and 2 in 24.1% and 17.2% of cycles, respectively) were observed. No significant clinical cardiotoxicity was observed in 12 of the 13 patients. One patient experienced a decrease in left ventricular ejection fraction (from 60% to 43%) at a cumulative doxorubicin dose of 400 mg/m2. Antitumor efficacy was evaluated in both phase I and phase II. Overall clinical responses included 10 complete (31.3%) and 15 partial (46.9%) responses, for an objective response rate of 78.1%. Six patients (18.8%) had stable disease. The median durations of objective and complete response were 9 and 7 months, respectively. The 78.9% objective response rate in the phase I trial (31.6% complete and 47.3% partial responses) suggests a dose response relationship: at paclitaxel dose > or = 190 mg/m2, all patients had an objective response (six complete and nine partial responses). These results confirm that doxorubicin followed by paclitaxel is active and should be tested as adjuvant treatment and in patients treated previously with anthracyclines.
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PMID:A phase I/II study of sequential doxorubicin and paclitaxel in the treatment of advanced breast cancer. 889 94

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is active against advanced breast cancer and anthracycline-resistant breast cancer. We assessed the efficacy and toxicity of doxorubicin followed by a 3-hour infusion of paclitaxel in women with advanced breast cancer. Participants could have received at most one prior adjuvant chemotherapy regimen, but no previous exposure to anthracyclines or taxanes was permitted. The patients were treated every 3 weeks with doxorubicin (50 or 60 mg/m2) followed 30 minutes later by paclitaxel (155, 175, or 200 mg/m2). After reaching the maximum cumulative doxorubicin dose, treatment could be continued with paclitaxel alone. Thirty women were included, of whom 29 were evaluable for response. The overall response rate was 83% (95% confidence interval, 64% to 94%), with 24% of patients attaining complete remission. Median response duration for complete responders was 8+ months (range, 4 to 13 months) and median time to progression was 9 months (range, 2 to 18 months). Main toxicities were neutropenia, paresthesia, nausea/vomiting, alopecia, myalgia, and cardiotoxicity. In 15 patients (50%), the left ventricular ejection fraction decreased to below normal levels; six patients (20%) developed congestive heart failure. In conclusion, the combination of doxorubicin and paclitaxel is highly active; dose-limiting toxicities are neutropenia, neuropathy, and cumulative cardiotoxicity.
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PMID:Doxorubicin and paclitaxel, a highly active combination in the treatment of metastatic breast cancer. 889 95

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has a broad spectrum of activity, but the optimal schedule has not yet been determined. As a phase-specific agent, more frequent administration theoretically may be more effective. We have previously demonstrated that a weekly schedule of paclitaxel used as a radiation sensitizer is well tolerated by outpatients. We therefore conducted a phase I study of weekly paclitaxel in patients with chemotherapy-naive metastatic non-small cell lung cancer to determine the maximum tolerated dose of this alternative schedule. In all, 26 patients were entered into this study through six paclitaxel dose levels (100, 125, 135, 150, 175, and 200 mg/m2/wk) administered weekly for 6 of 8 weeks. All patients had a performance status of 0 through 2, with a median age of 65 years (age range, 37 to 80 years). Sites of disease included lung, bone, liver, soft tissue, and brain. Of the 26 entered, 24 patients completed the first 8-week cycle and are evaluable for toxicity. Dose-limiting toxicity, which consisted of neutropenia, occurred in four of six patients at 200 mg/m2/wk and in two of six at 175 mg/m2/wk. Only one evaluable patient required admission for febrile neutropenia. Other toxicities included rash, pulmonary infiltrate, myalgia, neuropathy, and alopecia. Nine (38%) of the 24 patients demonstrated objective responses. One patient with stable disease completed 48 weeks of therapy. Others remain in active treatment. We conclude that the maximum tolerated dose of paclitaxel administered for 6 consecutive weeks of an 8-week cycle is 175 mg/m2/wk and is limited principally by neutropenia. The response rate with this schedule is encouraging and merits further investigation.
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PMID:Preliminary results of a phase I study of weekly paclitaxel infusion in patients with non-small cell lung cancer. 894 5

This study was initiated to evaluate the safety and efficacy of 3-weekly paclitaxel given at 225 mg/m2 over 3 hours without colony stimulating factor support in patients at their first relapse following adjuvant therapy for breast cancer. Thirty patients were entered into the study; all were assessable for response and toxicity. All patients had received adjuvant/neo-adjuvant chemotherapy; 22 patients had had prior hormonal therapy and 26 previous adjuvant radiotherapy. The group was characterized by a short time to first relapse (median 7.5 months (range 2-43)) and widespread disease, with 22 patients having multiple disease sites including: nodes (43%), skin and soft tissue (43%), liver (40%), lung (37%) and bone (50%). A total of 219 cycles of paclitaxel were given, with a median of eight per patient. The major non-haematological toxicities were: grade 3 alopecia (82% cycles), grade 2/3 arthralgia/myalgia (26%), grade 2/3 fatigue (16%) and grade 2/3 peripheral nervous system toxicity (12%). Haematological toxicity was mainly neutropenia of short duration, with grade 4 counts documented in 16% of cycles. Thrombocytopenia was minimal and there were no significant hypersensitivity reactions. The objective response rate was 60% (95% CI 42.5-77.5) with one complete response and 17 partial responses. The median duration of overall response was 30 weeks (range 15-75+ (95% CI 25-33)) with a median survival time for all patients of 42 weeks (range 1-124+). This study demonstrates that paclitaxel 225 mg/m2 is well tolerated as a 3-hour infusion and can be given safely in an outpatient setting without routine use of granulocyte colony stimulating factor. The response rate is encouraging and shows that this regimen is effective in this poor prognosis patient population.
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PMID:A phase II study of single agent paclitaxel in patients at first relapse following initial chemotherapy for breast cancer. 897 50

Low-dose, subcutaneous recombinant human granulocyte colony-stimulating factor (rHuG-CSF, Lenograstim) was administered to 40 cancer patients (17 men, 23 women) enrolled from two medical centers to verify its clinical effectiveness and safety. The patients' mean age was 50.3 +/- 14.9 years. In this study, there were 20 patients with non-Hodgkin's lymphoma, 10 with breast cancer and 10 with various other solid tumors. The patients first received a course of chemotherapy without rHuG-CSF (control cycle). All patients had at least one episode of neutropenia or leukopenia during the control cycle. rHuG-CSF (2 micrograms/kg/day) was given subcutaneously for 10 days during the study cycle starting on the fourth day of chemotherapy. The nadirs of absolute neutrophil counts (ANC) were 1.8 +/- 0.25 x 10(9)/L and 0.27 +/- 0.05 x 10(9)/L for the rHuG-CSF cycle and pre-rHuG-CSF control cycle, respectively. The number of days of ANC < 1 x 10(9)/L were 1.03 +/- 0.29 and 7.38 +/- 0.58 for rHuG-CSF and control cycles, respectively. The duration from nadir to recovery of ANC (> or = 2 x 10(9)/L) was 9.68 +/- 1.15 days in the rHuG-CSF cycle, vs 22.53 +/- 1.03 days in the control cycle (p < 0.0001). No patient withdrew from the study. Adverse events were mild, with 12.5% to 40% of patients developing myalgia, general malaise, back pain, anorexia or fever. These side-effects were tolerable in all cases. The biochemical abnormalities were subtle and negligible. rHuG-CSF 2 micrograms/kg/day given subcutaneously for 10 days beginning on the fourth day of chemotherapy is very effective (90%), safe and convenient.
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PMID:Clinical trial of low-dose rHuG-CSF in neutropenic cancer patients following anti-cancer chemotherapy. 899 Jul 72

Based on the high activity of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in non-small cell lung cancer (NSCLC) and the superior 1-year survival rates of patients with NSCLC treated with carboplatin, the Hellenic Cooperative Oncology Group initiated a phase II trial to investigate the efficacy and toxicity of the combination of both agents in patients with nonoperable stage III and IV NSCLC. Since July 1995, 31 eligible patients have entered into this study. All patients received paclitaxel 175 mg/m2 as a 3-hour infusion plus 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 (range, 29 to 73 years) and the median performance status was I (range, 0 to 2). Most of the patients had stage IV adenocarcinoma (19 patients), with poor differentiation (15 patients). The median number of prior chemotherapy cycles was two, with a range of one to six. Among 21 evaluable patients, seven achieved a partial response, 10 had stable disease, and four had progressive disease. It is too early for evaluation in nine patients. Grade 2/3 nonhematologic toxicities included alopecia (46.4%), neurotoxicity (3.3%), and myalgia/arthralgia (7.1%). Grade 2/3 neutropenia was experienced by 10.7% of patients, whereas grade 2 thrombocytopenia was seen in only 3.3%. One patient died following complications of severe allergic reaction. In conclusion, although this study is ongoing, it is clear that the combination of paclitaxel and carboplatin is effective and well tolerated in patients with nonoperable NSCLC.
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PMID:Paclitaxel and carboplatin in nonoperable non-small cell lung cancer. 899 91

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


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