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)

Docetaxel (Taxotere) is a new cytotoxic compound with a broad spectrum of activity in preclinical studies. This paper reports a phase II trial in patients with previously-treated small cell carcinoma of the lung. 34 patients received 100 mg/m2 of docetaxel in an intravenous infusion given over 1 h every 21 days. Seven partial responses were reported (25% of 28 evaluable patients). Duration of response was 3.5-12.6 months. Toxicities were predominantly neutropenia, alopecia and asthenia. Docetaxel is a new compound with activity in previously-treated patients with small cell lung cancer, and is suitable for evaluation in combination with other cytotoxic drugs active in this disease.
 ...
PMID:Activity of docetaxel (Taxotere) in small cell lung cancer. The Early Clinical Trials Group of the EORTC. 765 28

The aim of this study was to determine the usefulness of recombinant human granulocyte colony stimulating factor (r-metHuG-CSF) following conventional chemotherapy for small cell lung cancer. 130 previously untreated patients were randomised to receive either r-metHuG-CSF (230 micrograms/m2) or placebo on days 4-17 following CDE (cyclophosphamide, doxorubicin and etoposide) chemotherapy. Over all cycles, 53% of 64 patients on placebo and only 26% of 65 patients on r-metHuG-CSF had at least one experience of neutropenia with fever defined as a neutrophil count less than 1.0 x 10(9)/l and a temperature > or = 38.2 degrees C (P < 0.002). It resulted in a reduction in the requirement for parenteral antibiotics from 58% in placebo patients compared with 37% in the r-metHuG-CSF group (P < 0.02), and a significant reduction in the incidence of infection-related hospitalisation. Chemotherapy doses were reduced by 15% or more at least once in 61% of the placebo group compared with 29% in the r-metHuG-CSF group (P < 0.001). 47% of the patients treated with placebo and 29% of the patients treated with r-metHuG-CSF experienced at least one cycle with a delay of 2 days or more in the administration of chemotherapy (P < 0.04). r-metHuG-CSF was well tolerated. There were no significant differences between the two groups in terms of response or survival.
 ...
PMID:Recombinant granulocyte colony stimulating factor reduces the infectious complications of cytotoxic chemotherapy. 769 Nov 19

The aim of this study was to assess the efficacy and toxicity of intensive chemotherapy, administered without dose reduction, with cranial and thoracic radiotherapy given when possible as a single fraction in small cell lung cancer. 87 patients were eligible on the basis of good performance status, normal or near normal biochemistry and clinical staging, 73 limited and 14 extensive stage, computed tomography scanning was not mandatory. Six cycles of carboplatin, ifosfamide and etoposide with vincristine on day 15 at 4 weekly intervals were planned. Dosages were not reduced in response to myelosuppression. Prophylactic cranial irradiation (PCI) as a single fraction after the first cycle and thoracic irradiation (when possible as a single fraction) following the third cycle were delivered. Seventy-two per cent of patients completed the protocol. Complete response rate was 55% and 26% of patients had a partial response. The median nadirs of neutropenia were 0.5 x 10(9)/l and thrombocytopenia 14 x 10(9)/l, with 6% probable treatment-related deaths. Performance status and dyspnoea improved markedly to normal or near normal levels following the second course. Brain metastases occurred in 13% of patients. The median survival was 16.2 months with a 2-year survival of 31% (95% confidence interval, 24-41%) for a minimum follow-up of 26 months. These results compare favourably with other combined modality studies, using multiple radiotherapy fractions with cisplatin-based combinations and dosage reduction for patients staged in more anatomical detail. The toxicity spectrum and efficacy data could lead to the use of this chemotherapy regimen with haematopoietic growth factors and, in the future, peripheral blood progenitor cell rescue.
 ...
PMID:Therapy for small cell lung cancer using carboplatin, ifosfamide, etoposide (without dose reduction), mid-cycle vincristine with thoracic and cranial irradiation. 785 8

Taxol, a diterpene alkaloid isolated from the bark of Taxus brevifolia, has a unique mechanism of action. The drug promotes the formation of microtubule polymers in a cell, by reversibly and specifically binding the beta-subunit of tubulin. Taxol is administered intravenously by a 3-24-hour infusion at 3-week intervals. Myelosuppression, especially neutropenia, appears to be the dose limiting toxicity in solid tumours at 200-250 mg/m2. Furthermore, side effects such as sensory neurotoxicity (with typical numbness, tingling and painful paraesthesiae in the extremities), diarrhoea and alopecia appear frequently. Mucositis appears to be the non-haematological dose limiting side effect at 390 mg/m2 that has been determined in patients with leukaemia. Hypersensitivity reactions, which have been fatal in individual cases, might be schedule dependent. Furthermore, antiallergic prophylaxis must be given, although this precaution might not be considered to be fully protective. Phase I studies performed with combinations of taxol and cisplatin, doxorubicin or cyclophosphamide have indicated the feasibility of these regimens and show promise for future investigations. Addition of granulocyte-colony stimulating factor (G-CSF), aimed at modulating myelosuppressive toxicity, showed in Phase I studies that the taxol dose could be increased to 250 mg/m2, with peripheral neuropathy as the dose limiting toxicity. In Phase II studies, taxol has been shown to be effective, including producing complete tumour remission, in advanced drug refractory ovarian carcinoma (19%-36% response rate), previously treated patients with metastatic breast carcinoma (27%-62% response rate), advanced non-small lung cancer (21%-24% response rate), advanced small cell lung cancer (37% response rate) and advanced head and neck cancer (34% response rate).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Clinical, toxicological and pharmaceutical aspects of the antineoplastic drug taxol: a review. 790 88

Taxoids (paclitaxel and docetaxel) are a new class of cytotoxic agents. Their mechanism of action (enhanced polymerization of tubulin and inhibition of its depolymerization) acts thereby as mitotic spindle inhibitors. Significant experimental antitumor activity, although more marked with docetaxel, has been observed with both agents. Their main side-effects are reversible non cumulative neutropenia and alopecia; significant hypersensitivity reactions using cortico-steroids antiHT1/2 premedication are seen in < 5% of patients receiving paclitaxel as a pulsed (3 h) infusion; neurotoxicity appears dose-related; docetaxel can induce a peculiar skin toxicity often associated with edema. Paclitaxel at the recommended dose of 175 mg/m2 achieves responses in 20-30% of patients with relapsed ovarian carcinoma; its activity in advanced breast cancer although significant is clearly dose-related with an optimal dose still debatable; responses are observed in approximately 30% of patients with non small cell lung cancer (NSCLC). Docetaxel (100 mg/2) is active in first line treatment of advanced breast cancer (50-72% RR) as well as 2nd line treatment (> 40% RR); an activity in the range of that observed with paclitaxel is reported in NSCLC.
 ...
PMID:Taxoids: a new class of cytotoxic agents. 790 41

An early phase II clinical study of RP56976 (Docetaxel), a new anticancer agent of plant origin, was conducted in patients with primary pulmonary cancer as a multicentered study involving 28 Japanese institutions. Docetaxel was administered at an intravenous dose of 60 mg/m2 based on the results of a phase I clinical study, and efficacy and safety were examined. Of the 65 patients enrolled, 57 patients were evaluated to have completed the scheduled course of treatment by the Evaluation Committee. The antitumor effect in patients with non-small cell lung cancer was 21.4% (9/42). In patients not previously treated, the antitumor effect was 30.0% (6/20), in patients previously treated the antitumor effect was 13.6% (3/22), and in 13.3% (2/15) of patients with small cell lung cancer. This shows that docetaxel had an efficacy for non-small cell lung cancer. Hematological adverse reactions included leukopenia and neutropenia of Grade III or more as specified in the Adverse Event Reporting Form proposed by the Japan Society for Cancer Therapy in 53.3% (32/60) and 78.3% (47/60) patients, respectively. Other major adverse reactions included alopecia and anorexia. Neurological symptoms developed at a low frequency and were mild in severity.
 ...
PMID:[Early phase II clinical study of RP56976 (docetaxel) in patients with primary pulmonary cancer. Docetaxel Cooperative Study Group for Lung Cancer]. 797 21

Eight evaluable patients with cisplatin-resistant non-small cell lung cancer (6 patients), small cell lung cancer (1 patient), or both breast and ovarian cancer (1 patient) were entered on a study to determine whether the addition of nifedipine plus pentoxifylline to cisplatin-based chemotherapy would result in increased chemotherapy efficacy. No patient responded to treatment. Myelosuppression may have been augmented by the nifedipine and pentoxifylline (median granulocyte nadir, 0.3 x 10(9)/L). Two patients developed febrile neutropenia. Nifedipine and pentoxifylline had to be stopped in two evaluable patients due to hypotension, and three additional inevaluable patients withdrew from the study due to nifedipine-pentoxifylline toxicity before receiving their chemotherapy. There was no indication that other types of chemotherapy toxicity were increased by the addition of nifedipine and pentoxifylline. A major problem with the strategy followed in this protocol was that patients whose tumors had failed to respond to cisplatin-based regimens were often too ill to tolerate additional cisplatin, particularly when accompanied by nifedipine-associated hypotension.
 ...
PMID:Addition of pentoxifylline plus nifedipine to chemotherapy in patients with cisplatin-resistant cancers of the lung and other sites. 804 93

Taxotere (N-debenzoyl-N-tert-butoxycarbonyl-10-deacetyl Taxol; RP 56976; NSC 628503) is a semisynthetic analogue of Taxol. It is twice as active in inhibiting tubuline depolymerization and has a better in vivo activity on B16 melanoma, with responses in advanced colon 38 and PO3 adenocarcinoma. Sixty-five patients (49 women, 16 men), with a median age of 57 years, received 248 courses of Taxotere given as a 1-2-h i.v. infusion every 2 or 3 weeks. Ten distinct dose levels from 5 to 115 mg/m2 were studied. Dose-dependent, reversible neutropenia was the limiting toxicity. Delayed and cumulative skin reactions occurred beyond 70 mg/m2. Alopecia was observed in the majority of patients beyond 70 mg/m2. Four partial responses were achieved in patients with ovarian carcinoma, breast carcinoma, small cell lung cancer, and carcinoma with unknown primary. The pharmacokinetics of Taxotere, determined in 23 patients receiving 20 to 115 mg/m2, was linear. At the highest doses, the Taxotere plasma profile was typically triphasic, with a terminal half-life of 13.5 +/- 7.5 (SD) h, a plasma clearance of 21.1 +/- 5.3 liters/h/m2, and a distribution volume of 72 +/- 40 liters/m2. AUC correlated with the percentage decrease of neutrophils in a sigmoid Emax model. The renal excretion of unchanged Taxotere was very low (< 5% of the dose). The recommended dose for phase II trials with this schedule is 100 mg/m2 every 3 weeks.
 ...
PMID:Phase I and pharmacokinetic study of Taxotere (RP 56976; NSC 628503) given as a short intravenous infusion. 809 96

In small cell lung cancer, combination chemotherapy including agents such etoposide, teniposide, cisplatin, doxorubicin, ifosfamide, vincristine and cyclophosphamide continues to be the cornerstone of therapy. The importance of dose scheduling of etoposide with continuous treatment of 5 days' duration or more is becoming more and more clear. Complete or partial responses secondary to combination chemotherapy occur in 80-90% of all patients with median durations of 9 to 11 months. Median survival in these studies is unchanged, at present 11-16 months depending on the initial tumour stage. The optimum duration of treatment is still uncertain, but generally a period of 6 to 9 months is used. The use of G-CSF with combination chemotherapy leads to reductions in the incidence of fever, duration and severity of grade 4 neutropenia, and in the total number of days of treatment with i.v. antibiotics and days of hospitalization. No differences have been observed in response rates, duration of response or survival. Therapeutic results for epidermoid, cancer, adeno carcinoma, large cell carcinoma and mesothelioma are essentially unchanged. The treatment of patients with these tumours should continue to be considered experimental since no standard chemotherapy has as yet been developed, neither when given as single modality nor in combination with surgery or radiotherapy. Two studies published in 1991 comparing induction chemotherapy before irradiation versus irradiation alone have resulted in improvement of median and 2-year survival, while a third study did not show such an improvement. The fact remains that three-fourths of patients with local disease die within 3 years, and further improvements in both systemic and local treatment are needed.
 ...
PMID:Lung cancer. 831 12

Information on the kinetics of bone marrow (BM) myeloid precursors (BMMP) is required for integrating cancer chemotherapy with granulocyte-macrophage colony-stimulating factor (rhGM-CSF), with the aim of reducing neutropenia. Using bivariate flow-cytometric analysis of the in vivo incorporation of bromode-oxyuridine (BUDR) vs DNA content we have studied the kinetics of BMMP in 21 patients with SCLC during the first of six chemotherapy courses (etoposide, epirubicin, and cis-platinum, days 1-3, every 21 days), given alone (eight patients) or followed by rhGM-CSF (10 micrograms/kg/day s.c., days 4-14) as BM rescue (eight patients) or both preceded (days -17 to -7, as BM priming) and followed by rhGM-CSF (five patients). At 11-14 days after the start of these therapies there was an increase in the baseline proliferative activity of proliferating BMMP and a shortening in the time needed by the metamyelocyte to mature and to leave the marrow. Both effects were greater and were maintained to a significantly greater degree a week later in patients who received chemotherapy plus rhGM-CSF rescue than in those who received chemotherapy alone or rhGM-CSF priming alone. At day 11-14 the pretreatment median cell production rate of pBMMP was increased by 340%, 150%, and 183% and the maturation time was reduced by 80%, 45%, and 57%, respectively, in the three groups. A week later, the corresponding figures were 206%, 111%, and 157% and 50%, 18%, and 45%. Hence, an identical rhGM-CSF schedule is more effective in increasing the neutrophil production by BMMP when given following chemotherapy as BM rescue than before it as BM priming. In both the rescue and the priming schedule, the increase in proliferative activity of BMMP just at the end of rhGM-CSF stimulation was linked to both an increase in the labeling index and a reduction in duration of S-phase (TS), while a week later it was linked solely to reduction in TS. This could actually reduce one of the two kinetic targets of subsequently administered cytostatics, i.e., a high LI and a long time spent in S phase. From this study, accurate kinetic data can be obtained with the in vivo BUDR technique that are useful in scheduling rhGM-CSF.
 ...
PMID:Bone marrow myeloid cell kinetics during treatment of small cell carcinoma of the lung with chemotherapy not associated and associated with granulocyte-macrophage colony-stimulating factor. 838 46


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>