共查询到20条相似文献,搜索用时 15 毫秒
1.
A Fajac J Gligorov K Rezai P Lévy E Lévy F Selle K Beerblock D Avenin P Saintigny S Hugonin J-F Bernaudin F Lokiec 《British journal of cancer》2010,103(4):560-566
Background:
It can be hypothesised that inherited polymorphisms in the drug-transporter ABCB1 gene may interfere with interindividual variations in drug response in breast cancer patients. Docetaxel is a substrate for ABCB1 whose function has been shown to be modulated by oestrogen and progesterone.Methods:
Whether ABCB1 polymorphisms including T-129C, A61G, C1236T, G2677T/A and C3435T polymorphisms could account for variations in the disposition of docetaxel and whether menopausal status at the time of diagnosis might interact with this effect were analysed in women receiving neoadjuvant chemotherapy for breast cancer (n=86).Results:
A highly significant association was observed, but restricted to premenopausal women (n=53), between the pharmacokinetics of docetaxel and C3435T polymorphism, as patients with CC genotype had lower mean values of the area under the plasma concentration-time curve (AUC) of docetaxel than patients with CT and TT genotypes (P<0.0001). Comparison between pre- and postmenopausal women with the same C3435T genotype yielded a significant difference in docetaxel AUC only for CC genotype (P<0.0001).Conclusion:
These results suggest that C3435T polymorphism genotyping and menopausal status at the time of diagnosis might be useful when considering chemotherapy regimens including docetaxel in breast cancer patients. 相似文献2.
Uchiyama T Kanno H Ishitani K Fujii H Ohta H Matsui H Kamatani N Saito K 《Cancer chemotherapy and pharmacology》2012,69(6):1617-1624
Purpose
Docetaxel is one of the most widely used chemotherapy drugs for gynecological cancers. A dose-limiting factor of docetaxel is severe neutropenia, and previous reports showed that grade 4 neutropenia was observed in approximately 70 % of Japanese patients treated with docetaxel. In order to elucidate a valid biomarker for docetaxel-induced neutropenia, we analyzed 42 Japanese patients with gynecological cancers such as ovarian cancer and endometrial cancer of the uterus.Methods
As a first step, AUC of docetaxel was examined in 10 patients and 1,936 SNPs of 225 genes were genotyped using DMET Plus? genotyping systems.Results
The first screening revealed that 28 SNPs were associated with the AUC (P < 0.05), and we analyzed the associations between the 28 SNPs and neutrophil counts in the other 32 patients, with the result that CYP39A1 (rs7761731) was found to be the only SNP significantly associated (P = 0.049 OR = 9.0) with the incidence of grade 4 neutropenia among 28 SNPs.Conclusions
This SNP in CYP39A1 may be a useful biomarker for predicting the risk of docetaxel-induced neutropenia. 相似文献3.
Eric H. Kraut Christopher Rhoades Yilong Zhang Hao Cheng Josephine Aimiumu Ping Chen James Lang Donn C. Young Amit Agrawal Janet Dancey Kenneth K. Chan Michael R. Grever 《Cancer chemotherapy and pharmacology》2011,67(3):579-586
Purpose
This phase I study determined the maximal-tolerated dose, dose-limiting toxicities, pharmacokinetics, and recommended dose of erlotinib with docetaxel.Patients and methods
Twenty-eight patients with head and neck cancer were enrolled. Patients were orally given erlotinib (50?mg) daily plus 35?mg/m2 of docetaxel intravenously weekly?×?3 every 4?weeks. Dose escalation of erlotinib was in 50-mg increments until toxicity. Pharmacokinetics were studied with LC?CMS/MS, standard, and population pharmacokinetic methods.Results
Ninety-five courses were successfully given (median 3, range 1?C6). The most frequent side effects were diarrhea, fatigue, skin rash, anemia, and hypoalbuminemia. Dose de-escalation for both erlotinib and docetaxel was due to skin rash, neutropenia and/or severe infection with docetaxel to 25?mg/m2 and erlotinib to starting dose of 50?mg and re-escalation of docetaxel to 35?mg/m2. Responses were observed in 4/26 evaluable patients (100?mg erlotinib). In 24 patients, the mean Cmax and AUC erlotinib values increased with dose and following cumulative dosing (days 7 and 8 vs. day1, p?<?0.05). The CL/F (~7 L/h), V/F (~140?L), and t1/2 (~20?h) for erlotinib were similar to the reported. The mean AUC ratio of metabolite OSI-420 to erlotinib following repetitive dosing at 100?mg (+?or ?C?docetaxel) showed a ~50% increase (p?<?0.02), possibly suggesting self-enzyme induction. Population pharmacokinetic studies showed no significant covariate affecting erlotinib pharmacokinetics.Conclusions
The combination of erlotinib and docetaxel was associated with significant toxicity, which limited the amount of administered erlotinib. Dosing for phase II trials was docetaxel 35?mg/m2 and erlotinib 50?mg. The reason for excessive toxicity is not clear, but not due to change in pharmacokinetics. 相似文献4.
Islam R. Younis Daniel J. George Terence J. McManus Herbert Hurwitz Patricia Creel Andrew J. Armstrong Jing Jie Yu Kristina Bacon Gerald Hobbs Cody J. Peer William P. Petros 《Cancer chemotherapy and pharmacology》2014,73(5):991-997
Purpose
This study was conducted to evaluate potential pharmacokinetic interactions between docetaxel and atrasentan as part of a phase I/II clinical trial.Methods
Patients with prostate cancer were treated with intravenous docetaxel (60–75 mg/m2) every 3 weeks and oral atrasentan (10 mg) daily starting on day 3 of cycle 1 and then given continuously. The pharmacokinetics of both drugs were evaluated individually (cycle 1, day 1 for docetaxel; day 21 for atrasentan) and in combination (cycle 2, day 1 for both drugs). Pharmacogenomics of alpha-1-acid glycoprotein (AAG) were also explored.Results
Paired pharmacokinetic data sets for both drugs were evaluable in 21 patients. Atrasentan was rapidly absorbed and plasma concentrations varied over a fourfold range at steady state within a typical patient. The median apparent oral clearance of atrasentan was 17.4 L/h in cycle 1 and was not affected by docetaxel administration (p = 0.9). Median systemic clearance of docetaxel was 51.1 L/h on the first cycle and significantly slower (p = 0.01) compared with that obtained during co-administration of atrasentan, 61.6 L/h. Docetaxel systemic clearance in cycle 1 was 70.0 L/h in patients homozygous for a variant allele in AAG compared with 44.5 L/h in those with at least one wild-type allele (p = 0.03).Conclusion
Genetic polymorphism in AAG may explain some inter-patient variability in docetaxel pharmacokinetics. The systemic clearance of docetaxel is increased by approximately 21 % when given concomitantly with atrasentan; however, atrasentan pharmacokinetics does not appear to be influenced by docetaxel administration. 相似文献5.
Chikara Kunisaki Masazumi Takahashi Hirochika Makino Takashi Oshima Shoichi Fujii Ryo Takagawa Jun Kimura Takashi Kosaka Hidetaka A. Ono Hirotoshi Akiyama Kunio Kameda Fumihiko Kito Satoshi Morita Itaru Endo 《Cancer chemotherapy and pharmacology》2011,67(6):1363-1368
Purpose
We evaluated the efficacy and toxicity of biweekly S-1 and docetaxel combination therapy in patients with advanced gastric cancer.Methods
Patients with histologically proven, unresectable advanced or recurrent gastric cancer, a performance status (PS) of 0?C2 and no prior chemotherapy history were eligible for inclusion (n?=?45). Patients received a total of 215 treatment courses (median, 4; range, 2?C12) of S-1 oral administration twice daily for 1?week followed by a drug-free interval of 1?week. Docetaxel (40?mg/m2) was administered intravenously on days 1 and 15.Results
We observed 25 partial responses (55.6%) and one complete response (2.2%), resulting in an overall response rate of 57.8%. Twenty-four patients (53.3%) received second-line chemotherapy. Five patients (11.1%) underwent R0 gastrectomy during the course of the study. The median overall survival time was 15.3?months, the median time to progression was 6.9?months, and the median duration of response in 26 patients was 8.0?months. Neutropenia was the most frequently observed (40.4%) haematological toxicity at grades 3 and 4 and leucopenia was the second most common (29.8%). There were no treatment-related deaths.Conclusions
S-1 plus docetaxel combination therapy in an outpatient setting provided promising activity with acceptable adverse toxicities. 相似文献6.
Narita S Tsuchiya N Yuasa T Maita S Obara T Numakura K Tsuruta H Saito M Inoue T Horikawa Y Satoh S Habuchi T 《International journal of clinical oncology / Japan Society of Clinical Oncology》2012,17(3):204-211
Objectives
Docetaxel-based chemotherapy is effective in patients with castration-resistant prostate cancer (CRPC). This phase II study assessed the outcome and predictive factors for prognosis and toxicity following intermittent chemotherapy with docetaxel, estramustine phosphate, and carboplatin (DEC) in patients with CRPC.Methods
Thirty-five patients were treated with a DEC regimen that consisted of a 28-day cycle of drugs as follows: docetaxel (60?mg/m2 on day 1), carboplatin (AUC 5 on day 1) and estramustine phosphate (560?mg daily). Treatment was continued intermittently. The end point was to test the effect of DEC on the response rate and overall survival (OS). Statistical correlations between the outcomes and predictive factors, including clinical parameters and 8 single-nucleotide polymorphisms (SNPs) related to drug metabolism, were assessed.Results
Prostate-specific antigen levels decreased by more than 30% in 65.7% of the patients. The median OS following DEC was 17.8?months, and the median total time of chemotherapy holiday was 7.7?months (range 1.7?C35.8). On multivariate analysis, serum lactate dehydrogenase (LDH) was an independent prognostic factor for OS (p?=?0.007). On SNP analysis, patients carrying the TT genotype of the ABCB1 C3435T polymorphism showed a significantly more severe leukocytopenia during the first cycle of DEC therapy compared to patients with the CC?+?CT genotype (p?=?0.036).Conclusion
Combination chemotherapy with DEC has a potential effect on CRPC with acceptable toxicity. Serum LDH may be a promising predictor of prognosis, and the ABCB1 C3435T polymorphism may be a genetic predictor of the severity of leukocytopenia in patients with CRPC treated with DEC. 相似文献7.
Hosonaga M Ito Y Tokudome N Takahashi S Iwase T Hatake K 《Breast cancer (Tokyo, Japan)》2012,19(4):329-334
Background
Docetaxel is a key drug for metastatic breast cancer (MBC). In patients with MBC, the treatment objective is durable response with minimum toxicity. In Japan, the approved dose of docetaxel is 60?C70?mg/m2 every 3?weeks, whereas 75?C100?mg/m2 docetaxel is common in the West.Methods
We retrospectively examined the prevalence of edema in patients with MBC who were treated with docetaxel. Seventy-seven patients received docetaxel at a dose of 60?mg/m2 every 3?weeks with prophylactic premedication of dexamethasone, 8?mg daily for 3?days.Results
Median follow-up time was 28?months (range 4.3?C98). Overall response was 25% (95% CI 15?C34). Median time to progression and median survival time from the beginning of any systemic therapy for metastatic disease were 10 and 66?months, respectively. Neutropenia was the most common toxicity, with grade 3?C4 observed in 66%. Fifty-one percent of the patients experienced peripheral edema that could be controlled with oral diuretics. Grade 3 edema was observed in 4 patients only, and discontinuation because of edema was 9%. Other grade 3 or 4 toxicity was <5%. Median cumulative dose of docetaxel to onset of peripheral edema was 480?mg/m2 (range 60?C780), and median cumulative given dose was 600?mg/m2 (range 84?C2,928).Conclusions
These results suggest that treatment with docetaxel at 60?mg/m2 could be continued longer than the higher dose with manageable peripheral edema in patients with MBC. Further investigation is required to determine the superiority of low-dose docetaxel. 相似文献8.
George Simon 《American Journal of Cancer》2003,2(5):349-356
? Docetaxel and cisplatin are well established antineoplastic agents with activity against NSCLC. The combination exhibited additive cytotoxic activity against human NSCLC cell lines in vitro. ? In a large phase III trial in chemotherapy-naive patients with advanced NSCLC, survival with docetaxel plus cisplatin was statistically noninferior to that with the control regimen of vinorelbine plus cisplatin. Overall response rate with docetaxelplus cisplatin was significantly higher than with the control. ? Median survival times, tumor response rates, and median time to progression for patients receiving docetaxel plus cisplatin were similar to those for patients receiving paclitaxel plus cisplatin in another large phase III trial. ? Neutropenia was the most common grade 3/4 adverse event in docetaxel/cisplatin recipients (≥69% of patients in the two large phase III trials); these proportions were not significantly different from those for patients receiving controls. Grade 3/4 vomiting, nausea, or anemia were significantly less common than with vinorelbine plus cisplatin, whereas hypersensitivity reactions were significantly more common than with paclitaxel plus cisplatin. Table
Table. Features and properties of docetaxel (Taxotere®) plus cisplatin (Platinol®) 相似文献
9.
Michelle A. Rudek Cathy Y. Chang Kenneth Steadman Michael D. Johnson Naveen Desai John F. Deeken 《Cancer chemotherapy and pharmacology》2014,73(4):729-736
Purpose
Non-AIDS-defining cancers (NADCs) now exceed rates of AIDS-defining cancers in HIV-positive patients. Treatment of NADCs may be complicated by drug–drug interactions between antiretrovirals and chemotherapy. Docetaxel is a widely used anticancer agent that is primarily metabolized by CYP3A4 enzymes and used to treat NADCs. A preclinical in vivo assessment was performed to gain a better understanding of CYP3-mediated drug–drug interactions between antiretrovirals and docetaxel, as well as to assess any alterations in gene expression with these combinations.Methods
Docetaxel (20 mg/kg i.v.) was administered to male FVB mice in the presence and absence of dexamethasone (10 mg/kg p.o. ×4d), efavirenz (25 mg/kg p.o. ×4d), ketoconazole (50 mg/kg p.o.), or ritonavir (12.5 mg/kg p.o.). At various time points, plasma and liver tissue were harvested. Docetaxel concentrations were determined by LC/MS/MS. Pharmacokinetic parameters were calculated. Liver tissue RNA was used to evaluate alterations in Cyp3a11 and Abcb1a gene expression.Results
Docetaxel exposure was altered by CYP3A4 inhibitors but not by inducers. The CYP3A4 inducers efavirenz and dexamethasone did not have a significant effect on docetaxel exposure (AUC). However, the CYP3A4 inhibitors ritonavir and ketoconazole resulted in a 6.9- and 3.1-fold increase in AUC, respectively. Alterations in gene expression did not account for the altered docetaxel exposure.Conclusions
Docetaxel exposure was significantly altered by CYP3A4 inhibitors. Until a definitive clinical trial is performed, docetaxel should be used with caution in patients on a ritonavir-containing antiretroviral regimen or an alternative antineoplastic therapy or antiretroviral regimen should be considered. 相似文献10.
Barrie R. Cassileth Naiyer Rizvi Gary Deng K. Simon Yeung Andrew Vickers Stacey Guillen Derek Woo Marci Coleton Mark G. Kris 《Cancer chemotherapy and pharmacology》2009,65(1):67-71
Purpose
To study a commonly used Astragalus-based herbal formula previously found effective in non-small cell lung cancer (NSCLC) on the pharmacokinetics of docetaxel in patients with NSCLC.Methods
Patients with advanced NSCLC who progressed after prior platinum-containing chemotherapy were accrued and received docetaxel at 35 mg/m2 for 3 weeks followed by 1 week of rest. At 4 days prior to the second dosing, Jinfukang was given orally. Pharmacokinetic studies of initial-dose docetaxel (in the absence of Jinfukang) and the third dose (in the presence of Jinfukang) were compared.Results
Of the 24 patients enrolled, 21 started Jinfukang and docetaxel. Jinfukang had no significant impact on the pharmacokinetics of docetaxel. Median time to progression or withdrawal from treatment was 7 weeks. Twelve patients were removed from study for progression of disease; nine patients withdrew.Conclusions
Jinfukang did not alter the pharmacokinetics of docetaxel nor appear to affect survival in this study. 相似文献11.
Saik Urien Fran?ois Doz Carole Giraud Elisabeth Rey Jean-Claude Gentet Pascal Chastagner Gilles Vassal Nad��ge Corradini Anne Auvrignon Pierre Leblond Herv�� Rubie Jean-Marc Treluyer 《Cancer chemotherapy and pharmacology》2011,67(3):597-603
Purpose
A randomized clinical trial examined whether dexamethasone administration prior to ondansetron followed by etoposide and carboplatin infusions, and single-nucleotide polymorphisms (SNPs) of CYP3A4, CYP3A5 and MDR1 genes could modify etoposide pharmacokinetics in pediatric patients.Methods
Patients, 67 children, aged 14?weeks to 16.7?years, were treated for various malignancies and received either 3- or 5-day courses of etoposide and carboplatin: these two drugs were always administered after ondansetron infusion but combined or not with dexamethasone 5?mg/m2/day 30?min prior to etoposide infusion. Population pharmacokinetics was modeled using a non-linear mixed effect model program (Monolix version 31?s).Results
Etoposide pharmacokinetics was ascribed to a 2-compartment model. The most significant covariate effect was bodyweight (BW), so the parameters were standardized to a 70-kg BW using the allometric ? or 1 power model for clearance (CL, Q) or volume terms (V), respectively. The population means for clearance and central volume of distribution were 2.05?l/h/70?kg and 9.21?l/70?kg with the corresponding between-subject variabilities, 0.26 and 0.28. Dexamethasone treatment had no effect on CL, either at the first or at the last administration occasion. CYP3A and MDR1 examined SNPs had no significant effect.Conclusion
Pharmacokinetics of etoposide was influenced by BW on an allometric basis in this pediatric population. Dexamethasone did not influence etoposide pharmacokinetics during these 3?C5?days courses. These results should allow a better individualization of etoposide dosing in children. 相似文献12.
K L Mahon H-M Lin L Castillo B Y Lee M Lee-Ng M D Chatfield K Chiam S N Breit D A Brown M P Molloy G M Marx N Pavlakis M J Boyer M R Stockler R J Daly S M Henshall L G Horvath 《British journal of cancer》2015,112(8):1340-1348
Background:
Docetaxel improves symptoms and survival in metastatic castration-resistant prostate cancer (CRPC). However, ∼50% of patients are chemoresistant. This study examined whether changes in cytokine levels predict for docetaxel resistance in vitro and in a clinical cohort.Methods:
PC3 cells or their docetaxel-resistant subline (PC3Rx) were co-cultured with U937 monocytes, with and without docetaxel treatment, and cytokine levels were measured. The circulating levels of 28 cytokines were measured pre-/post cycle 1 of docetaxel from 55 men with CRPC, and compared with prostate-specific antigen (PSA) response.Results:
PC3Rx-U937 co-culture expressed more cytokines, chiefly markers of alternative macrophage differentiation, compared with PC3-U937 co-culture. Docetaxel treatment enhanced cytokine production by PC3Rx-U937 co-culture, while reducing cytokine levels in PC3-U937. In patients, changes in the levels of seven circulating cytokines (macrophage inhibitory cytokine 1 (MIC1), interleukin (IL)-1ra, IL-1β, IL-4, IL-6, IL-12 and IFNγ) after cycle 1 of docetaxel were associated with progressive disease (all P<0.05). The combination of changes in MIC1, IL-4 and IL-6 most strongly predicted PSA response (P=0.002).Conclusions:
In vitro studies suggest docetaxel resistance is mediated, at least in part, by cytokines induced by the interaction between the docetaxel-resistant tumour cells and macrophages. Early changes in circulating cytokine levels were associated with docetaxel resistance in CRPC patients. When considered together, these data suggest a significant role for the inflammatory response and macrophages in the development of docetaxel resistance in CRPC. 相似文献13.
Agust�� Barnadas Ricard Mes��a Margarita Majem Ram��n Galiana Antonio L��pez-Pousa Jos�� M. de Vega Mireia Margel�� Vicente Valent�� Llu��s Anglada Ariadna Lloans�� Antonio Arellano 《Clinical & translational oncology》2011,13(4):254-260
Introduction
Concurrent chemotherapy and radiotherapy is recommended for the treatment of locally advanced unresectable head and neck (H&N) cancer.Objective
The primary purpose of the Phase I part of the study was to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended dose (RD) of docetaxel with hyperfractionation radiotherapy. The primary objective of the Phase II part was to determine the response rate to the RD of treatment and, secondarily, to assess the toxicity of the schedule, time to progression, duration of response and overall survival (OS).Materials and methods
Patients (n=9 in Phase I; n=19 in Phase II) had unresectable H&N cancer. The starting docetaxel dose was 20 mg/m2 plus hyperfractionated radiotherapy. Ramping of docetaxel was 5 mg/m2 if MTD was not reached.Results
MTD of docetaxel was 20 mg/m2. Limiting toxicities were grade 4 pneumonia and grade 4 mucositis. The RD was 15 mg/m2. Phase II initial response was 76% (CR=18%; PR=9%); updated response was 89% (CR=59%; PR=29%). The median progression-free survival was 7.8 months (95%CI: 0?C22.3) and the median OS was 15.1 months (95%CI: 0?C35.9). Grade 3?C4 toxicities included mucositis (91%), pneumonia (27%) and fatigue (27%). There were 5 toxic deaths (2 from intestinal perforation, 3 from pneumonia).Conclusions
Weekly docetaxel+hyperfractionation radiotherapy is active but with high toxicity rates and, hence, this treatment regimen would be difficult to justify. 相似文献14.
Eun Kyung Cho Ji-Young Park Kyung Hee Lee Hong Suk Song Young Joo Min Yeul Hong Kim Jin-Hyoung Kang 《Cancer chemotherapy and pharmacology》2014,73(1):9-16
Purpose
The aim of this study was to compare CKD-810 (test docetaxel) with Taxotere® (reference docetaxel) in terms of pharmacokinetics and safety for patients with advanced or metastatic carcinoma.Methods
A randomized, open-label, two-way crossover study was conducted in eligible patients. Patients received with reference or test drugs of 75 mg/m2 docetaxel by intravenous infusion for 60 min in the first period and the alternative drug in the second period with a washout of 3 weeks. Plasma concentrations of docetaxel were determined by validated high-performance liquid chromatography coupled to tandem mass spectrometry detection. Pharmacokinetic parameters, including the maximum plasma concentration (C max) and the area under the concentration–time curve (AUC), were determined by non-compartmental analysis.Results
A total of 44 patients were included in the study, 21 patients received test drug and 23 received reference drug for the first cycle. The C max of docetaxel was 2,658.77 ng/mL for test drug and 2,827.60 ng/mL for reference drug, and two drugs showed no difference with a statistical significance. Time to reach C max (T max) of CKD-810 (0.94 h) versus reference docetaxel (0.97 h) was also not significantly different. Other pharmacokinetic parameters including the plasma AUC, elimination half-life, and total body clearance exhibited similar values without a significant difference. The most common grade 3 or 4 toxicity was neutropenia (CKD-810 19.5 or 29.3 %; reference docetaxel 14.6 or 41.5 %). Febrile neutropenia was experienced by only one patient in each group. Two patients died of progression of disease during the study.Conclusion
Docetaxel anhydrous CKD-810 use with patients suffering advanced or metastatic solid malignancies was equivalent to reference docetaxel in terms of pharmacokinetic parameters and safety profile. Additionally, the test and reference drug met the regulatory criteria for pharmacokinetic equivalence. 相似文献15.
Koizumi W Nakayama N Tanabe S Sasaki T Higuchi K Nishimura K Takagi S Azuma M Ae T Ishido K Nakatani K Naruke A Katada C 《Cancer chemotherapy and pharmacology》2012,69(2):407-413
Purpose
We conducted a phase II study to evaluate the efficacy and safety of a triplet regimen of docetaxel, cisplatin, and S-1 in patients with unresectable or recurrent gastric cancer.Methods
Docetaxel (40?mg/m2) and cisplatin (70 or 60?mg/m2) were given on day 1 of a 28-day cycle. S-1 (40?mg/m2) was given twice daily on days 1?C14. Treatment with this regimen was continued for a maximum of 6 cycles. Subsequently, patients with no disease progression received a combination of docetaxel and S-1.Results
Fifty-nine patients were enrolled. The median number of administered cycles was 8 (range, 1?C25). Because some patients had serious myelosuppression and renal dysfunction with 70?mg/m2 of cisplatin, dose of cisplatin was reduced to 60?mg/m2 after 19 patients had been treated. Common severe toxic effects of grade 3 or 4 were leukocytopenia (44%), neutropenia (72%), anemia (15%), and febrile neutropenia (14%). The overall response rate of this group was 81% (95% confidence interval (CI), 71?C91%). The median overall survival and progression-free survival were 18.5 (95% CI, 15.6?C21.5) and 8.7 (95% CI, 6.7?C10.7) months, respectively.Conclusions
Triplet of docetaxel, cisplatin, and S-1 is a well-tolerated and highly active regimen for advanced or recurrent gastric cancer. A 60?mg/m2 of cisplatin is as effective as 70?mg/m2 of cisplatin. 相似文献16.
Toshikado Kaneta Ken-ichi Fujita Yuko Akiyama Kaori Kawara Yu Sunakawa Asuka Kawachi Ken Shimada Yasutsuna Sasaki 《Cancer chemotherapy and pharmacology》2014,74(3):539-547
Purpose
Aprepitant, a CYP3A4 substrate, effectively prevents chemotherapy-induced nausea and vomiting. Oral aprepitant 1 h before intravenous infusion of docetaxel does not change the pharmacokinetics of docetaxel. In practical combination chemotherapy, oral aprepitant is given 3 h before docetaxel infusion. We examined effects of this treatment schedule on the pharmacokinetics of docetaxel.Methods
Inhibition constant (K i) of aprepitant for CYP3A-mediated docetaxel hydroxylation was estimated with human liver microsomes. A prospective, open-label, triple-crossover study was performed in balanced groups of cancer patients who received three consecutive cycles of docetaxel, consisting of docetaxel alone (A), docetaxel plus aprepitant given 3 h before docetaxel (B1), and docetaxel plus aprepitant given 1 h before docetaxel (B2). Three treatment arms were studied: Arm I, B1 followed by A and B2, respectively; Arm II, B2 followed by A and B1, respectively; and Arm III, A followed by B2 and B1, respectively. Pharmacokinetics of docetaxel and aprepitant were evaluated on day 1.Results
The K i value was estimated to be 9.82 µM. Eligible patients (20) were allocated to Arm I (8), Arm II (7), or Arm III (5). On combined analysis of data from all patients assigned to Arms I–III, there were no significant differences among cycles A, B1, and B2 in the area under the plasma concentration–time curve (AUC) of docetaxel or the docetaxel AUC divided by actual dose. Pharmacokinetics of aprepitant showed large interindividual variability.Conclusion
Administration of aprepitant 3 h before docetaxel infusion did not alter the pharmacokinetics of docetaxel. 相似文献17.
Jin Young Kim Young Rok Do Keon Uk Park Min Kyung Kim Kyung Hee Lee Sung Hwa Bae Hun Mo Ryoo Jin Ho Baek Hong Suk Song 《Cancer chemotherapy and pharmacology》2010,66(1):31-36
Objective
The objective of this study was to evaluate the efficacy and toxicity of docetaxel and cisplatin combination chemotherapy in patients with metastatic esophageal cancer.Methods
Patients with untreated metastatic squamous cell esophageal cancer, which was histologically proven with at least one measurable lesion, were eligible for the study. Docetaxel 70 mg/m2 and cisplatin 70 mg/m2 were intravenously given on day 1 of 21 days schedule.Results
From December 2004 to December 2007, total of 39 patients (M/F = 39/0) were enrolled. The median age was 65 years. Thirty-four patients were evaluable for response. There were 3 (7.7%) complete remission, 10 (25.6%) partial remission, 11 (28.2%) stable disease, and 10 (25.6%) progression disease. The objective tumor response rate was 33.3% in intention-to-treat (ITT). Median PFS was 5.0 months and median survival was 8.3 months. Median number of cycles administered was 3. The relative dose intensity of docetaxel and cisplatin was 92 and 91%, respectively. This treatment was comparatively tolerated with grade 3/4 neutropenia in 20.5%/10.3%, grade 3 infection in 2.6% of patients.Conclusion
Docetaxel plus cisplatin combination chemotherapy showed promising antitumor activity with manageable toxicities in patients with metastatic squamous esophageal cancer. 相似文献18.
Hidenori Tamegai Teruo Kaiga Mitsugu Kochi Masashi Fujii Noriaki Kanamori Yoshiaki Mihara Tomoya Funada Hiroko Shimizu Daijo Jinno Tadatoshi Takayama 《Cancer chemotherapy and pharmacology》2013,71(3):727-731
Purpose
The purpose of this study was to investigate whether intravenous (i.v.) administration allowed docetaxel to penetrate ascites in gastric cancer patients with peritoneal dissemination.Patients and methods
Twelve patients with disseminated gastric carcinoma were enrolled in the study. All patients received docetaxel-containing drug regimens: i.v. administration of 40 mg/m2 docetaxel in 6 patients, and 60 mg/m2 in the remainder. Docetaxel concentrations in the plasma and ascites were measured.Results
Docetaxel was detected in the ascites of 4 patients in the 40 mg/m2 group and 5 patients in the 60 mg/m2 group. The highest concentration of docetaxel in plasma was detected at immediately after administration (median: 1,660 ng/mL, 501–2,560 ng/mL), after which it gradually decreased. The highest concentration of docetaxel in ascites was observed at ~7 h after administration and varied among cases (median: 18 ng/mL, 11–52 ng/mL).Conclusion
Intravenous administration allows to penetrate ascites in gastric cancer patients with peritoneal dissemination. 相似文献19.
Keng Shen Beihua Kong Yunong Gao Lingying Wu Ziting Li Yile Chen Mengda Li Yongliang Gao Ding Ma Zhilan Peng 《临床肿瘤与癌症研究(英文版)》2009,6(6):387-393
OBJECTIVE Pegylated liposomal doxorubicin (PLD; CAELYX ), a novel formulation of doxorubicin with enhanced therapeutic efficacy and reduced toxicity, has demonstrated improved progression-free survival in recurrent or refractory ovarian cancer. The objective of this open-label, noncomparative, observational study was to determine the efficacy and safety of PLD monotherapy or combination therapy with carboplatin for patients with cancer. recurrent or refractory ovarian METHODS Sixty-two patients with recurrent or refractory ovarian cancer who completed a platinum-based chemotherapy regimen and demonstrated platinum sensitivity for first-line treatment at least 6 months prior to study entry were enrolled in 20 centers in China. PLD was given as monotherapy (50 mg/m2 infused over 60 minutes) or as combination therapy (30 mg/m2 1-hour infusion) with carboplatin (area under the curve 5 mg.min/mL 1-hour infusion) on day 1 every 28 days for 4 cycles. The primary endpoint was objective response (OR) rate or CA-125 level. Secondary endpoints included time to response, time-to-progression, health-related quality of life, and safety. RESULTS Overall, 48% of the 62 evaluable patients achieved a confirmed OR. More patients receiving PLD and carboplatin achieved an OR vs the PLD monotherapy group (63% vs. 37%). The median time to response and disease progression was 58.5 days and 56.0 days, respectively. Overall and drug-related adverse events were reported for 39% and 34%, respectively. The most commonly reported adverse events were stomatitis (22.6%) and palmar-plantar erythroderma (9.7%). Two deaths were reported. CONCLUSION PLD is an effective and well tolerated agent in women with recurrent or refractory epithelial ovarian cancer. 相似文献
20.
Eiran Warner Leonard Liebes Benjamin Levinson Andrea Downey Amy Tiersten Franco Muggia 《The oncologist》2014,19(3):250-250