Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Paclitaxel is a plant product isolated from the bark of the Western yew (Taxus brevifolia) that promotes the formation and stabilization of microtubules. This leads to growth arrest in the G2/M phase of the cell cycle. Paclitaxel has demonstrated significant antineoplastic activity in different tumor types, most notably in ovarian and breast carcinoma. In two Phase II trials (Eastern Cooperative Oncology Group [ECOG]/M.D. Anderson) in patients with previously untreated Stage IIIB-IV non-small cell lung cancer (NSCLC), response rates of 21% and 24% were reported. We are performing a Phase II trial investigating the efficacy of paclitaxel in patients with inoperable Stage IIIB-IV NSCLC. Forty-three patients were treated, 31 males and 12 females, with a median age of 59 years (range, 29-75), ECOG performance status 0-2, Stage IIIB 30%, Stage IV 70%. Patients were treated every 3 weeks with 225 mg/m2 as a 3-h infusion with standard premedication. Preliminary efficacy results from 37 patients include partial remissions in eight (21.6%) patients, no change in 22 (59.5%) and disease progression in seven (19%) patients. Eight patients are still receiving therapy. The hematologic toxicities (n = 43) were mild, and no World Health Organization (WHO) Grade 4 neutropenia was observed. Nonhematologic toxicities were Grade 1/2 polyneuropathy in 97.6%, Grade 1-3 myalgia/arthralgia in 76%, and Grade 1-3 nausea/vomiting in 18.6% of the patients. In conclusion, paclitaxel is an active single agent in this patient population. Mild hematologic toxicities were observed in the 3-h infusion setting (compared with 24-h infusion) and therapy was well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Phase II study with paclitaxel for the treatment of advanced inoperable non-small cell lung cancer. 755 41

We conducted a phase I trial in advanced NSCLC to determine the optimal dosage of the new active drug paclitaxel (Taxol), in combination with high-dose ciplastin (CDDP). Taxol was infused over 3 h, followed by CDDP given over 30 min with hyperhydration. Main criteria of selection were the presence of metastatic or locally relapsing pathologically proven NSCLC, stage IIIB or IV and no prior therapy. Out of 17 treated patients, eight objective responses (47%) were documented. Significant but transient neutropenia was observed in steps III and IV. In seven patients, who received more than three courses, treatment was discontinued for severe polyneuropathy in five, cancer progression in one and unrelated disease in one. In conclusion, paclitaxel plus cisplatin, although active, was associated with severe late neurological toxicity prohibiting the administration of multiples courses.
 ...
PMID:Dose-finding study of paclitaxel (Taxol) plus cisplatin in patients with non-small cell lung cancer. European Lung Cancer Working Party. 755 43

Although paclitaxel (TAXOL) appears to be one of the most promising antineoplastic agents of the last decade, with demonstrated activity in advanced and refractory ovarian, breast, lung, and head and neck cancers, most clinical oncologists have had little experience with the agent. This is largely the result of the initially limited supply of paclitaxel and other obstacles encountered during early clinical development that restricted the drug's availability to a few investigational centers. Although a high incidence of major hypersensitivity reactions due to the Cremophor EL vehicle used in formulation disrupted and almost terminated the clinical development of paclitaxel, hypersensitivity reactions are no longer a serious problem consequent to the advent of effective premedication regimens and longer administration schemes. Instead, neutropenia is the principal toxicity of paclitaxel. At clinically relevant doses, absolute neutrophil count nadirs are severely depressed in most patients. The duration of severe neutropenia, however, is usually brief; treatment delays for unresolved hematologic toxicity are rare, and absolute neutrophil count nadirs are constant with repetitive dosing, suggesting that neutropenia is not cumulative. Asymptomatic sinus bradycardia has occurred in up to 29% of patients in phase II trials, and other cardiac disturbances, including atrioventricular conduction and bundle branch blocks, ventricular tachycardia, and possible ischemic manifestations, have been reported in approximately 3% of patients. Cardiac disturbances have primarily been noted in studies that used cardiac monitoring to more effectively detect and manage major hypersensitivity reactions. Although sinus bradycardia and conduction blocks appear to represent true toxicities, ventricular tachycardia and ischemic manifestations, which have largely been observed in patients with preexisting cardiac disease, may not be due to paclitaxel. In view of the lack of clinical significance of the cardiac effects and their infrequent occurrence, cardiac monitoring during paclitaxel is not recommended for patients without cardiac risk factors. However, until precise risk factors can be defined, patients with a significant antecedent cardiac history are generally not considered to be good candidates for paclitaxel therapy. Neurotoxicity, characterized principally by peripheral neurosensory manifestations, has generally been of mild to moderate severity, even in heavily pretreated patients at paclitaxel doses < or = 200 mg/m2. However, some patients have developed a severe sensory-motor polyneuropathy at higher doses of paclitaxel (given as a single agent or in combination with cisplatin). Patients with an antecedent peripheral neuropathy or coexisting medical illnesses associated with peripheral neuropathy (such as diabetes mellitus and substantial prior alcohol use) appear to be especially prone to developing peripheral neuropathy.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Clinical toxicities encountered with paclitaxel (Taxol). 810 12

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has demonstrated significant antineoplastic activity against different tumor types, notably ovarian and breast carcinoma. Two phase II trials of 24-hour paclitaxel infusions in chemotherapy-naive patients with stage IIIB or IV non-small cell lung cancer (NSCLC) reported response rates of 21% and 24%. Leukopenia was dose limiting: as many as 62.5% of patients experienced grade 4 leukopenia. We investigated the efficacy and toxicity of a 3-hour paclitaxel infusion in a phase II trial in patients with inoperable stage IIIB or IV NSCLC. The 58 patients treated (41 men and 17 women) had a median age of 59 years (age range, 25 to 75) and a performance status of 0 through 2. Most patients (72.4%) had stage IV NSCLC. Paclitaxel 225 mg/m2 was infused over 3 hours every 3 weeks with standard prophylactic premedication. Of 50 patients evaluable for response, 12 (24%) had partial remission, 26 (52%) had no change, and 12 had disease progression (24%). Hematologic toxicities were mild: only one patient (2%) developed grade 3 or 4 neutropenia, while 29% had grade 1 or 2. Grade 1 or 2 polyneuropathy affected 56% of patients while only one (2%) experienced severe polyneuropathy. Similarly, grade 1 or 2 myalgia/arthralgia was observed in 63.2% of patients, but only 14.3% experienced grade 3 or 4. Nausea and vomiting were infrequent, with 14% of patients experiencing grade 1 or 2 and only 2% experiencing grade 3 or 4. Paclitaxel is thus an active single agent in this patient population, with a 3-hour infusion proving comparably effective to a 24-hour infusion and superior in terms of the incidence of hematologic and nonhematologic toxicity. Further phase II studies with paclitaxel combined with other drugs active against NSCLC are indicated, and phase III studies comparing paclitaxel with standard chemotherapy remain to be completed.
 ...
PMID:Chemotherapy of advanced inoperable non-small cell lung cancer with paclitaxel: a phase II trial. 864 66

We performed a clinical phase II trial of the combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and cisplatin in patients with locally advanced (stage IIIB) or metastatic non-small cell lung cancer (NSCLC), using a 3-hour infusion of paclitaxel followed by a 1-hour infusion of cisplatin. Treatment was repeated every 21 days, for a maximum of six cycles. The patients received paclitaxel 175 mg/m2 followed by cisplatin 75 mg/m2. At present, 52 chemotherapy-naive patients with stage IIIB (17.3%) or stage IV (82.7%) NSCLC have been entered into this ongoing trial. Ten (19%) of the patients are women and 42 (81%) are men. With 197 courses of chemotherapy given, all 52 patients are evaluable for toxicity. Hematologic toxicities were moderate: World Health Organization (WHO) grade 3 or 4 neutropenia occurred in 38.7% of the cycles (47.7% of patients), and WHO grade 3 or 4 thrombocytopenia was observed in 1.5% of cycles (3.8% of patients). Other toxicities consisted mainly of WHO grade 2 or 3 alopecia and nausea/vomiting. World Health Organization grade 1 or 2 polyneuropathy occurred in 30.4% and grade 3 or 4 only in 1% of all courses. Of 40 patients evaluable for response, a complete remission was noted in one patient, a partial remission occurred in 13 patients (32.5%), stable disease was seen in 14 patients (35%), and disease progressed in 12 patients (30%). These results suggest that the combination of paclitaxel and cisplatin is active and tolerable in the treatment of NSCLC. The efficacy of the combination seems high in this poor-prognosis population.
 ...
PMID:Paclitaxel and cisplatin in patients with non-small cell lung cancer: results of a phase II trial. 894 3

Carboplatin/etoposide is an active regimen in the treatment of small cell lung cancer. This phase II trial evaluated whether adding paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to this two-drug combination might increase its efficacy. Since April 1996, 55 patients were entered into the ongoing protocol. To date, 35 patients are evaluable for efficacy and toxicity. Most of the evaluable patients are male (28). The patients' median age is 60 years (range, 36 to 74 years); 32 patients have Eastern Cooperative Oncology Group performance status ratings of 1, and the balance are Eastern Cooperative Oncology Group performance status 0. All patients had limited-stage disease. Patients received paclitaxel 175 mg/m2 via 1-hour intravenous infusion on day 1, carboplatin dosed to an area under the concentration-time curve of 5, also on day 1, and oral etoposide 100 mg on days 2 through 8. Overall, 31 patients responded to paclitaxel/carboplatin/etoposide therapy, including complete response in 13 patients (37.1%) and partial response in 18 patients (51.4%). Disease was stable in three patients (8.6%) and disease progressed in one (2.0%). Hematologic toxicity included neutropenia (World Health Organization grade 3 in 24.1% of patients, grade 4 in 31.3%), anemia (4% grade 3, no grade 4), and thrombocytopenia (3.2% grade 3, 2.1% grade 4). Nonhematologic adverse events included minor nausea/vomiting (1.5% grade 3, 9.2% grade 2), polyneuropathy (2.3% grade 2, 17.5% grade 1), and myalgia/arthralgia (8.2% grade 2, 16.4% grade 1). Paclitaxel/carboplatin/etoposide is active in small cell lung cancer with moderate toxicity and good subjective tolerance. There were no life-threatening hematologic or nonhematologic complications in this phase II trial.
 ...
PMID:Paclitaxel, carboplatin, and oral etoposide: a phase II trial in limited-stage small cell lung cancer. 933 Nov 41

A 74-year-old man with diabetes mellitus type II, retinopathy and polyneuropathy suffered from exophthalmus, ptosis and diplopia. Magnetic resonance imaging and computer tomography showed a space-occupying process in the right orbital apex. An extranasal ethmoidectomy accompanied by an orbitotomia revealed the presence of septated hyphae. Aspergillus fumigatus was grown from the tissue. After surgical removal of the fungal masses, therapy with amphotericin B (1 mg kg(-1) body weight) plus itraconazole (Sempera, 200 mg per day) over 6 weeks was initiated. Five months later the patient's condition deteriorated again, with vomiting, nausea and pain behind the right eye plus increasing exophthalmus. Antifungal therapy was started again with amphotericin B and 5-fluorocytosine. Neutropenia did not occur. The patient became somnolent and deteriorated, a meningitis was suggested. Aspergillus antigen (titre 1:2, Pastorex) was detected in liquor. Anti-Aspergillus antibodies were not detectable. Both the right eye and retrobulbar fungal masses were eradicated by means of an exenteratio bulbi et orbitae. However, renal insufficiency and an apallic syndrome developed and the patient died. At autopsy, a mycotic aneurysm of the arteria carotis interna dextra was detected. The mycotic vasculitis of this aneurysm had caused a rupture of the blood vessel followed by a massive subarachnoidal haemorrhage. In addition, severe mycotic sphenoidal sinusitis and aspergillosis of the right orbit were seen, which had led to a bifrontal meningitis.
 ...
PMID:Case report. Mycotic arteritis due to Aspergillus fumigatus in a diabetic with retrobulbar aspergillosis and mycotic meningitis. 1176 8

We describe the case of a 58-year-old woman with autoimmune enteropathy associated with thyroiditis, gastritis, transitory neutropenia, sicca syndrome and severe axonal polyneuropathy of autoimmune origin. Enterocyte autoantibodies were not detected. However, predisposition to autoimmune disease was indicated by the presence of high titres of anti-gastric parietal cell, anti-thyroglobulin, anti-thyroid peroxidase and anti-neutrophil antibodies. CD4+ and CD8+ lymphocytes were equally distributed in the lamina propria of the small intestine, but CD8+ cells were highly represented among intraepithelial lymphocytes.
 ...
PMID:Autoimmune enteropathy in an adult with autoimmune multisystemic involvement. 1237 24

In patients with advanced breast cancer, treatment with paclitaxel and doxorubicin has been shown to produce impressive overall response rates (up to 94%) and to prolong overall survival significantly over a combination of fluorouracil (5-FU), doxorubicin, and cyclophosphamide (Cytoxan, Neosar) in one prospective phase III clinical study. These results have been challenged, however, by other data demonstrating no survival advantage for taxane-based therapies. In addition, the combination of paclitaxel and doxorubicin has repeatedly been shown to be complicated by the development of treatment-related congestive heart failure, when cumulative doxorubicin doses exceed 300-360 mg/m2. Consequently, attempts have been made to increase the complete remission rate and overall survival resulting from first-line treatment of metastatic breast cancer without compromising patient safety. Gemcitabine (Gemzar)--a relatively effective, well-tolerated and partially non-cross-resistant antitumor compound with limited toxicity--represents an attractive alternative to paclitaxel/anthracycline combinations. Initial studies of combination therapy with gemcitabine and paclitaxel have produced an average response rate of 52%, with time to progression ranging between 7.0 and 14.5 months. Three-drug regimens containing gemcitabine, an anthracycline, and paclitaxel have been tested in phase II studies and have produced impressive response rates of 82.9% with gemcitabine, doxorubicin, and paclitaxel and 92% with gemcitabine, epirubicin (Ellence), and paclitaxel (GET). The Central European Cooperative Oncology Group has evaluated the GET regimen vs a regimen containing 5-FU, epirubicin, and cyclophosphamide (FEC) in a randomized, prospective phase III study. Interim toxicity analysis showed that the GET regimen was well tolerated but produced more grade 4 neutropenia (64% vs 42%, P = .084) and significantly more grade 4 thrombocytopenia (12% vs 0%; P < .001) than FEC. Anaphylactic/allergic reactions, peripheral polyneuropathy, nausea, and cardiotoxicity constituted rare events and did not exceed grade 1 or 2 in severity. Although final data from this phase III trial are not yet available, preliminary analysis suggests the GET regimen represents an attractive option for patients with advanced breast cancer.
 ...
PMID:Gemcitabine, anthracycline, and taxane combinations for advanced breast cancer. 1476 4

In order to downstage locally advanced breast cancer, neoadjuvant chemotherapy consisting of intravenous vinorelbine 25 mg/m plus epirubicin 75 mg/m given on day 1 and oral vinorelbine 60 mg/m on day 8 was administered every 3 weeks for four courses. On day 2, all patients received a single subcutaneous injection of pegfilgrastim (6 mg). From March 2004 to June 2005, 22 patients were enrolled. Patients characteristics were: median age, 53 years (range: 39-70 years); postmenopausal, 7/22; clinical TNM stage, T2 (n=14), T3 (n=8), N0 (n=17) and N1 (n=5). The median number of courses was four (range: two to six courses) with full dose intensity. National Cancer Institute grade 3 haematological toxicities observed were neutropenia in 9% of patients, anaemia in 13% of patients and thrombocytopenia in 9% of patients; no toxicity grade 4 occurred. Two patients (9%) registered grade 2 polyneuropathy; no cardiac failure was observed. Conservative surgery was performed in 14 patients (63%). All patients were evaluable for response: complete pathological response was documented in three patients (13.6%); three patients (13.6%) obtained more than 75% of tumour size reduction; 11 other patients (50%) had 50% of tumour size reduction; stable disease was observed in five patients (22.7%). The present findings indicate that vinorelbine in combination with epirubicin is an effective and safe treatment in locally advanced breast cancer: this regimen obtained more than 50% of tumour size reduction in 77% of patients; the use of pegfilgrastim allowed full dose intensity. Oral vinorelbine on day 8 offers greater convenience to the patient by reducing the need for intravenous injection and the time spent in hospital.
 ...
PMID:Alternating intravenous and oral vinorelbine plus epirubicin with pegfilgrastim as neoadjuvant treatment of locally advanced breast cancer. 1700 Nov 82


1 2 Next >>