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排序方式: 共有334条查询结果,搜索用时 15 毫秒
1.
F Elferink W J van der Vijgh W W ten Bokkel Huinink J B Vermorken I Klein B Winograd M K Knobf G Simonetti H E Gall J G McVie 《British journal of cancer》1987,56(4):479-483
Pharmacokinetics of the cis-platin analog ethylenediaminemalonatoplatinum(II) (JM-410) was studied in 28 cycles of 19 patients during the phase I study of this drug. The drug was administered intravenously by short-term (10-60 min) infusion. Doses ranged from 20 to 1,200mg m-2. JM-40 was determined in plasma ultrafiltrate and urine by HPLC. Platinum (Pt) concentrations were determined in plasma, plasma ultrafiltrate, urine and red blood cells by atomic absorption spectrometry up to 5 days after administration of the drug. Ultrafilterable Pt could be determined up to 45 days after the infusion in one patient sampled over such a long period. Pharmacokinetics of JM-40 showed a linear behaviour. The final half-life of total Pt in plasma was 4.1 +/- 0.9 days. The disposition of JM-40 was similar to that of ultrafilterable Pt in respect to t1/2 alpha (10 and 13 min), t1/2 beta (44 and 57 min), volumes of distribution Vc (11 and 121) and Vss (17 and 201), systemic clearance (256 and 223 ml min-1), renal clearance (69 and 73 ml min-1) and metabolic clearance (183 and 154 ml min-1). During the first 6 h 27 +/- 9% of the administered dose was excreted as JM-40. Cumulative platinum excretion in the urine amounted to 29 +/- 13% and 60 +/- 13% over the first 6 h, 24 h and 5 days, respectively. The uptake of platinum in red blood cells was limited, comprising only 0.24 +/- 0.12% of the administered dose. Although JM-40 and carboplatin are structurally closely related, pharmocokinetics and toxicity of JM-40 were more similar to cis-platin than to carboplatin. 相似文献
2.
R. de Wit G. Stoter D. T. Sleijfer S. B. Kaye P. H. de Mulder W. W. ten Bokkel Huinink P. J. Spaander M. de Pauw R. Sylvester 《British journal of cancer》1995,71(6):1311-1314
We have investigated whether an alternating induction chemotherapy regimen of PVB/BEP is superior to BEP in patients with poor-prognosis testicular non-seminoma. A total of 234 eligible patients were randomised to receive an alternating schedule of PVB/BEP for a total of four cycles or four cycles of BEP. Poor prognosis was defined as any of the following: lymph node metastases larger than 5 cm, lung metastases more than four in number or larger than 2 cm, haematogenic spread outside the lungs, such as in liver and bone, human chorionic gonadotrophin > 10,000 IU l-1 or alphafetoprotein > 1000 IU l-1. The complete response (CR) rates to PVB/BEP and BEP were similar, 76% and 72% respectively (P = 0.58). In addition, there was no significant difference in relapse rate, disease-free and overall survival at an average follow-up of 6 years. The 5-year progression-free and survival rates in both treatment groups were approximately 80%. The PVB/BEP regime was more toxic with regard to bone marrow function; the frequencies of leucocytes below 1000 microliters-1, leucocytopenic fever and platelets below 25,000 microliters-1, throughout four cycles were 28% vs 5% (P < 0.001), 16% vs 5% (P = 0.006), and 10% vs 1% (P = 0.001) respectively. Neuropathy also occurred more often in the PVB/BEP arm: 47% vs 25% (P = 0.001). This study shows that an alternating regimen of PVB/BEP is not superior to BEP and that it is more myelo- and neurotoxic. 相似文献
3.
S B Kaye J Wanders M Clavel J Verweij M J Piccart J F Smyth W W Ten Bokkel Huinink D J Wagener I R Judson F Cavalli 《Annals of oncology》1992,3(5):406-408
A total of 91 eligible patients with metastatic cancer have been treated in a series of phase II trials of the novel pentacyclic pyrroloquinone, fosquidone. Tumour types were breast (24), ovary (25), head and neck (21) and melanoma (21). All patients, except those with melanoma had received prior chemotherapy. The drug was given intravenously as a 20 min infusion, at the dose of 120 mg/m2 on days 1 to 5 of a 3 week cycle. Treatment was well tolerated; the only significant side-effects being mild headaches and generalised musculo-skeletal pains. Response was assessed after 2 cycles of therapy. Only one patient (with head and neck cancer) achieved an objective partial response, lasting 6 weeks. A total of 12 patients demonstrated stable disease for a median duration of 15 to 20 weeks. Using this schedule of administration, fosquidone has no significant antitumour activity in this group of tumours. 相似文献
4.
J H Beijnen L T Vlasveld J Wanders W W ten Bokkel Huinink S Rodenhuis 《The Annals of pharmacotherapy》1992,26(4):488-490
OBJECTIVE: A case in which a possible cisplatin interference with lithium pharmacokinetics is evaluated. DATA SYNTHESIS: A 36-year-old woman with disseminated cervical cancer and multiple metastatic lesions in both kidneys was being treated with five courses of bleomycin, vindesine, mitomycin C, and cisplatin. The patient had also been taking lithium carbonate for the management of a manic-depressive disorder. Serum and urinary lithium concentrations were measured daily during the first course of chemotherapy and on a periodic basis during and between the consecutive courses. Lithium concentrations remained within the therapeutic range during the first course and increased later in association with deterioration of the patient's renal function secondary to progressive disease in both kidneys. This required dose adjustments of lithium. CONCLUSIONS: Lithium therapy should be guided by serial serum concentrations in such patients. 相似文献
5.
R A Valdés Olmos W W ten Bokkel Huinink J C Greve C A Hoefnagel 《Clinical nuclear medicine》1992,17(3):163-167
In six patients with doxorubicin-related cardiotoxicity, the severity of decrease in left ventricle ejection fraction (LVEF) was associated with faster myocardial I-123 MIBG washout rates. In four patients with severely decreased LVEF (range 19% to 28%), the 4-hour washout rate varied from 43% to 56%. In two patients with moderate cardiotoxicity (LVEF 42% and 43%), the washout rates were 37% and 35%, respectively. In contrast, in another patient thought to have initial left ventricular dysfunction (LVEF dropped from 66% to 54%), the myocardial I-123 MIBG retention rate was not reduced (6% washout). Subsequent continuation of chemotherapy in this patient was without complication. Reduced I-123 MIBG uptake in the left ventricle generally correlated with areas with abnormal Fourier amplitude values, but in one of the patients with moderate cardiotoxicity, the I-123 MIBG uptake was not reduced in a region with loss of amplitude, indicating dysfunction but probably no myocardial denervation. Analysis of the regional myocardial retention in patients with cardiotoxicity showed no significant difference in the I-123 MIBG washout rates of both segments with or without loss of amplitude. These data suggest that in spite of a localized loss of ventricular function demonstrated by radionuclide angiocardiography, doxorubicin-related cardiotoxicity appears to be based on a global process of myocardial adrenergic derangement. 相似文献
6.
S Rodenhuis L T Vlasveld R Dubbelman R Roodbergen J H Schornagel J Wanders S P Israels E Bais W W Ten Bokkel Huinink D J Richel 《Annals of oncology》1992,3(6):463-467
Eleven patients with testicular cancer, either relapsing after or refractory to cisplatin-based chemotherapy, underwent salvage chemotherapy with high-dose carboplatin (800 mg/m2 on day 1) and high-dose etoposide (500 mg/m2 on days 1, 3 and 5). A total of 21 courses were administered. The major toxicity consisted of profound myelosuppression. There were two toxic deaths, both caused by infection during neutropenia. Bone marrow recovery was usually complete around day 26 (range 19-129). Other toxicities included mild mucositis, nausea and vomiting, and alopecia. No significant neurotoxicity or hearing loss were observed and only one patient had a moderate decrease in renal function. Nine of ten evaluable patients responded, with one complete remission, 6 partial remissions with normalization of tumor markers, and two partial remissions with over one log decrease of tumor markers. The duration of these remissions was not evaluable, since only three evaluable and responding patients did not receive additional therapy after HD-CE. All three relapsed after discontinuing chemotherapy. HD-CE has activity in relapsing or refractory testicular cancer and can be administered without bone marrow support. The regimen may thus be suitable to be used as a remission induction regimen prior to consolidation with intensive chemotherapy and autologous bone marrow transplantation. 相似文献
7.
Human leukocyte antigen matching and fetal loss: results of a 10 year prospective study 总被引:6,自引:0,他引:6
Ober C; Hyslop T; Elias S; Weitkamp LR; Hauck WW 《Human reproduction (Oxford, England)》1998,13(1):33-38
The role that maternal and fetal human leukocyte antigen (HLA) genes play
in pregnancy is unknown, but it has been suggested that fetuses whose HLA
alleles do not differ from maternal alleles (i.e. histocompatible fetuses)
are more likely to be aborted than fetuses with HLA alleles that differ
from maternal alleles (i.e. histoincompatible fetuses). To elucidate the
role of HLA compatibility in pregnancy, we tested the hypothesis that
couples who match for HLA alleles or haplotypes would have reduced
fertility because only these couples could produce histocompatible fetuses.
We conducted a 10 year prospective study of HLA matching and pregnancy
outcome in 111 Hutterite couples, providing information on 251 pregnancies.
A logistic regression analysis was performed to determine the effects of
HLA matching at HLA regions and loci on pregnancy outcome (fetal loss
versus delivery). Significantly increased fetal loss rates were observed
among couples matching for the entire 16-locus haplotype (P = 0.002). Among
the individual loci, loss rates were increased among couples matching for
HLA-B (P = 0.019), HLA-C (P = 0.033) and the complement component, C4 (P =
0.043). We interpret these results as evidence that matching for the entire
16-locus haplotype and/or alleles at an HLA-B-linked locus confers
significant risk for fetal loss.
相似文献
8.
James Cassidy Martin A. Graham Wim Ten Bokkel Huinink Cathy McDaniel Albert Setanoians Elaine M. Rankin David J. Kerr Stanley B. Kaye 《Cancer chemotherapy and pharmacology》1993,31(5):395-400
Summary LL-D491941 is a new cytotoxic antibiotic selected for clinical phase I study because of its impressive pre-clinical anti-tumour activity and its low toxicity profile in experimental animals. A total of 15 patients were treated in centres in Glasgow and Amsterdam at doses ranging from 0.25 to 4 mg/m2. One minor response was noted in a patient with colonic carcinoma. The study was suspended following the discovery of unexpected cardiotoxicity. As this toxicity was not consistent with the standard (EORTC) European Organisation for Research and Treatment of Cancer toxicology profile, we chose to investigate the pharmacokinetics of LL-D491941 in mice and humans in more detail to try to explain this phenomenon. A major difference in plasma protein binding was discovered between mice and patients, with a suggestion of non-linear kinetics being noted at higher doses in humans. It is likely that these differences in drug handling account for the unexpected and serious toxicity encountered in this trial. 相似文献
9.
Fumoleau P Seidman AD Trudeau ME Chevallier B Ten Bokkel Huinink WW 《Expert opinion on investigational drugs》1997,6(12):1853-1865
Breast cancer is the most common malignancy in women, accounting for about 18% of female cancers, and over half a million new cases are diagnosed worldwide each year. Its incidence increases with age and is currently rising. Although the increased availability of screening programs has allowed earlier detection and treatment of primary breast cancers, many patients relapse with metastases after apparently successful treatment of their primary tumor and over 15,000 women in the UK and about 50,000 in the USA die from advanced disease each year. The natural course of breast cancer is very variable even after the development of metastases, and depends on a variety of tumor characteristics and prognostic factors. This is reflected in the large number of treatments currently employed. However, despite this wide choice and considerable research over the years, treatment of metastatic breast cancer (MBC) prolongs average survival times only slightly. Current therapy is aimed at achieving a balance between producing maximal tumor shrinkage to produce the most effective possible palliation of symptoms, and minimizing adverse effects. Anticancer chemotherapy is the preferred option in patients who do not respond to hormones, those with hormone-independent tumors, those with aggressive breast cancer subtypes. A variety of anticancer chemotherapy regimens, using both single and combined agents, have been shown to be effective in achieving tumor regression in MBC. Anthracyclines (doxorubicin, epirubicin) are the most active of the established monotherapies, typically producing response rates of 50-60% during initial (first-line) treatment for metastatic disease, but being effective in fewer than 25% of patients requiring second-line therapy. The drawbacks of anthracyclines include dose-limiting cumulative cardiotoxicity and the development of resistant tumor clones after the use of anthracyclines for adjuvant or first-line therapy, especially if subsequent courses are required within a year. The success of these established chemotherapeutic agents depends greatly on the number and location of metastatic sites. Lymph node and soft tissue secondaries tend to respond well, while visceral metastases (especially in the liver) carry a particularly poor prognosis despite treatment. The outlook for patients with metastases involving more than two organ systems is also bleak. Although some patients can live for years with metastatic disease, the average survival time in patients with MBC is 18-24 months, while in those with liver metastases, life expectancy averages only 6 months. High-dose anticancer chemotherapy with granulocyte-colony stimulating factor (G-CSF) or autologous bone marrow transplantation has allowed the dose intensity of anthracyclines to be increased, and has improved the response rate to about 70% in selected patients with MBC. However, this approach has not been proven to improve survival, involves the risk of greater toxicity and drug-related mortality, and patients with reduced clearance of anthracyclines due to hepatic dysfunction from liver metastases may not be suitable candidates. A number of new anticancer agents have also recently been introduced in an attempt to improve on the performance and avoid the tolerability problems associated with anthracyclines. Among these, antitubulin agents (taxoids and vinorelbine) have shown highly promising activity in MBC. This paper reviews the preclinical, phase I and phase II data for one taxoid, docetaxel. Docetaxel (Taxotere) belongs to the taxoid class of cytotoxic agents, the development of which began more than 20 years ago. In 1971, paclitaxel (Taxol) was identified as the active compound of the crude extract of the bark of the Pacific Yew tree Taxus brevifolia. However, at that time the development of paclitaxel was hampered because of the limited source of the drug and difficulties with isolation, extraction and formulation. The second active taxoid, docetaxel, was isolated by Potier et al. in 1986. Docetaxel is prepared from a non-cytotoxic precursor, extracted from the needles of the European Yew tree Taxus baccata, that is condensed with a chemically-synthesized side-chain. As the docetaxel precursor is freely available because of the regenerating capacity of the needles the development of docetaxel has thus been rapid. 相似文献
10.
Verweij J.; Wanders J.; Nielsen A. L.; Pavlidis N.; Calabresi F.; Huinink W. ten Bokkel; Bruntsch U.; Piccart M.; Franklin H.; Kaye S. B.; On behalf of the EORTC Early Clinical Trials Group 《Annals of oncology》1994,5(4):375-376
PURPOSE:: To test the antitumor activity of Elsamitrucin in metastaticcancer of the breast, colon and rectum, non-small cell lungand ovary. PATIENTS AND METHODS:: Eligibility required histologically proven cancer. Patientswith colorectal or non-small cell lung cancer could not havereceived prior chemotherapy. Patients were entered if WHO PSwas 2 and organ functions were normal. Treatment consisted ofElsamitrucin 25 mg/m2/week given as a 510 min infusionfor at least 36 weekly doses. RESULTS:: One hundred and five patients entered the studies, 97 were eligible,94 are evaluable for toxicity and 75 for response. Toxicitymainly consisted of mild nausea/vomiting, and less frequentlyreversible hepatotoxicity and malaise. No objective responseswere seen. CONCLUSION:: Elsamitrucin at this dose and schedule is not an active drugin metastatic breast cancer, colorectal cancer, non-small celllung cancer or ovarian cancer. Elsamitrucin, phase II, breast, colorectum, nonsmall cell lung, ovary 相似文献