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Anne-Joy M de Graan Alex Sparreboom Peter de Bruijn Evert de Jonge Bronno van der Holt Erik A C Wiemer Jaap Verweij Ron H J Mathijssen Ron H N van Schaik 《British journal of clinical pharmacology》2015,80(3):560-568
Aim
Taxanes are anti-cancer agents used to treat several types of solid tumours. They are metabolized by cytochrome P450 (CYP) 3A, displaying a large pharmacokinetic (PK) variability. In this study, we evaluated the endogenous CYP3A4 marker 4β-hydroxycholesterol (4β-OHC) as a potential individual taxane PK predictor.Methods
Serum 4β-OHC and cholesterol concentrations were determined in 291 paclitaxel and 151 docetaxel-treated patients, and were subsequently correlated with taxane clearance.Results
In the patients treated with paclitaxel, no clinically relevant correlations between the 4β-OHC or 4β-OHC : cholesterol ratio and paclitaxel clearance were found. In the patients treated with docetaxel, 4β-OHC concentration was weakly correlated with docetaxel clearance in males (r = 0.35 P = 0.01, 95% CI 0.08, 0.58). Of the 10% patients with taxane outlier clearance values, 4β-OHC did correlate with docetaxel clearance in males (r = 0.76, P = 0.03, 95% CI 0.12, 0.95).Conclusion
There was no clinical correlation between paclitaxel clearance and the CYP3A4 activity markers 4β-OHC or the 4β-OHC : cholesterol ratio. A weak correlation was observed between 4β-OHC and docetaxel clearance, but only in males. This endogenous CYP3A4 marker has limited predictive value for taxane clearance in patients. 相似文献4.
Clinical benefits of non‐taxane chemotherapies in unselected patients with symptomatic metastatic castration‐resistant prostate cancer after docetaxel: the GETUG‐P02 study 下载免费PDF全文
Florence Joly Remy Delva Loïc Mourey Emmanuel Sevin Emmanuelle Bompas Lionel Vedrine Alain Ravaud Jean‐Christophe Eymard Nicole Tubiana‐Mathieu Claude Linassier Nadine Houede Aline Guillot François Ringensen Oana Cojocarasu Bruno Valenza Alexandra Leconte Stéphanie Lheureux Bénédicte Clarisse Stéphane Oudard 《BJU international》2015,115(1):65-73
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AbstractSeasonal variations in taxane concentrations in Taxus canadensis. Marsh. (Canada yew) were measured at 15 sampling dates from September 2004 to September 2005 by clipping 3-year-old shoots from the same 15 plants. Four age classes of needles and stems were separated and individually weighed and analyzed for the three major taxanes in T. canadensis.: 10-deacetylbaccatin III (10-DAB III), 9-dihydro-13-acetylbaccatin III (9-DHAB III), and paclitaxel (PAC). The dry weight fraction of each foliage age class decreased with increasing age; that is, proportionately more young than old foliage (current > current + 1 year > current + 2 year) was present in a 3-year-old stem. The ratio of needle:stem dry weight also decreased with increasing foliage age. Taxane concentrations varied widely, depending on the tissue, its age, and time of year. Peak concentrations were observed for a short period at the end of the growing season (August–September). The lowest taxane levels were found during the period of active growth: April through July. PAC and 9-DHAB III concentrations were higher in needles, but young stems contained the highest amounts of 10-DAB III. Levels of all three taxanes were higher in young than in old stems, likely due to increasing amounts of taxane-poor stem wood. Composite taxane concentrations were calculated for 3-year-old foliage from the component needle and stem weights and taxane analyses. It is suggested that summer harvesting between April and July (the low point in annual taxane levels) yields the poorest quality biomass, and harvesting from August onward is preferable. 相似文献
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R. Sánchez-Escribano Morcuende J. E. Alés-Martínez P. M. Aramburo González 《Clinical & translational oncology》2007,9(7):459-464
Purpose Cisplain-gemcitabine is a synergistic chemotherapy (CT) combination highly proven in a broad spectrum of epithelial neoplasms
and shows a non-cross-resistance profile with the most active drugs in metastatic breast cancer (MBC). We have conducted an
exploratory study to determine if treatment with low doses of a combination of fixed-rate gemcitabine infusion and cisplatin
was clinically meaningful in women relapsing after a minimum of 2 prior lines of CT for advanced disease (range 2–6), which
had to have necessarily included both anthracyclines and taxanes. Another goal was to find the optimal individual schedule
by adjusting frequency and dosage according to patient tolerability.
Patients and methods From May 2002 to November 2003, 22 patients with relapsed advanced BC and a minimum of two prior CT lines were offered treatment
with gemcitabine (G) (initial dose 750 mg/m2, or 600 mg/m2 if the patient had received more than two previous CT lines) plus cisplatin (P) (initial dose 30 mg/m2, or 20 mg/m2 in case of ≥3 prior CT lines) on days 1 and 8 of a 21-day cycle. Treatment was postponed to day 15 if it could not be given
on day 8, without dose reduction. If treatment could not be given on day 15, a 20% dose reduction was allowed and treatment
given the next week. Further dose reductions were allowed as needed up to a maximum of three. Treatment continued until disease
progression or intolerable toxicity. Median age was 54.5 years (35–75). Median Karnofsky was 90 (range 80–90). Median number
of prior CT lines was 3 (2–6). 90.9% of patients had received adjuvant CT. All had prior anthracyclines and taxanes. Other
agents used included 5-FU/eniluracil, MTA, RPR 109881A, trastuzumab, cisplatin, VP16, vinorelbine, capecitabine and irinotecan.
72.7% had received radio-therapy and 68.1% hormonal therapy (median 2 lines, range 1–4).
Results Partial responses (PR) were seen in 9.1% of patients and stable disease (SD) in 36.4%. Clinical Benefit Rate (PR+SD) was derived
in 45.5% of patients. Median time to progression was 4 months (95% CI, 3–5) in general and 6 months (95% CI, 4–8) in patients
with clinical benefit. Median survival for the entire group was 8 months (95% CI, 5–11) and 19 months when clinical benefit
was obtained (95% CI, 11–25). Patients received a median of 8.5 CT administrations (range, 2–45). Forty-three percent of doses
were delayed. Sixteen out of 22 patients needed a delay and/or reduction of initial dose. Cisplatin and gemcitabine doses
were reduced in 75% and 62% of all cycles, respectively. Sixteen out of 22 patients needed a delay and/or reduction of initial
dose. Toxicities grade >3 were neutropenia 35% and thrombocytopenia 15%. All other toxicities were grade 2 or less, including
sensorial neuropathy (30%), asthenia (34%), nausea/vomiting (20%) and oral mucositis (15%). There were no treatment-related
deaths. Reasons for discontinuation were progression (18 patients), death (3 patients) and patient decision (1 patient).
Conclusion Weekly cisplatin-gemcitabine with flexible downwards individual tailoring is a safe and effective salvage treatment in heavily
pretreated MBC patients with good PS. 相似文献
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