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OBJECTIVETo investigate the potential benefit of reintroducing docetaxel chemotherapy in patients with progressive metastatic castration-resistant prostate cancer (mCRPC) who had initially responded to first-line docetaxel-based regimen.
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t Several methods for quantification of docetaxel have been described mainly using HPLC. We have developed a new : isocratic HPLC method that is as sensitive and simpler than previous methods, and applicable to use in clinical pl1...
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t Several methods for quantification of docetaxel have been described mainly using HPLC. We have developed a new : isocratic HPLC method that is as sensitive and simpler than previous methods, and applicable to use in clinical pl18m1acokinetic analysis. Plasma samples are spiked with paclitaxel as internal standard and extracted manually on activated cyanopropyl end-capped solid-phase extraction columns followed by isocratic r~versed.phase HPLC and UV detection at 227 nm. Using this system, the retention times for docetaxel and paclitaxel are 8.5 min and 10.5 min, respectively, with good resoh'tion and without any interference from endogenous plasma constituents or docetaxel metabolites at these retention times. The total run time needed is only 13 min. The lower limit of quantification is 5 ng/ml using 1 ml of plasma. The validated quantitation range of the method is 5-1000 ng/ml with RSDsS10%, but plasma concentrations up to 5000 ng/ml can be accurately measured using smaller aliquots. This method is also suitable for the determination of docetaxel in urine samples under the same conditions. The method has been used to assess the pharmacokinetics of docetaxel during a phase 1/11 study of docetaxel in combination with epirubicin and cyclophosphamide in patients with advanced cancer.
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Hormone-resistant prostate cancer (HRPCa) is a debilitating and lethal condition. In men with nonmetastatic HRPCa experiencing a rise in prostate-specific antigen (PSA) under andro gen-deprivation therapy, the median bone metastas...
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Hormone-resistant prostate cancer (HRPCa) is a debilitating and lethal condition. In men with nonmetastatic HRPCa experiencing a rise in prostate-specific antigen (PSA) under andro gen-deprivation therapy, the median bone metastasis-free survival is between 2 and 3 yr. In men with metastatic HRPCa, the average median time to the first skeletal-related event is 10 mo and the average survival is <2 yr . For many years, sequential hormonal manipulations, including estramustine phosphate, radiotherapy, and mitox-antrone were the only available options, aiming essentially at relieving pain and improving quality of life.
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Background: We evaluated the possible advantages of a docetaxel (DCT) rechallenge strategy in metastatic castration-resistant prostate cancer (mCRPC) patients, also given the possible earlier positioning of this treatment option i...
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Background: We evaluated the possible advantages of a docetaxel (DCT) rechallenge strategy in metastatic castration-resistant prostate cancer (mCRPC) patients, also given the possible earlier positioning of this treatment option in the modern scenario. Patients & methods: All mCRPC patients planned for DCT chemotherapy rechallenge in our institutions were evaluated. Results: Of 128 patients, 98 achieved disease control on the initial DCT round. After a treatment holiday of 8.3 months, the 98 responsive patients underwent a second DCT round, with 56 cases achieving again disease control. After a 5.7-month off-treatment period, 32 of these cases underwent a third DCT round, and 16 responded. Lastly, after a further 4.2-month treatment holiday, eight patients underwent a fourth DCT round and two responded. Median time to definitive disease progression for the whole population was 16.4 months. Conclusions: Rechallenge with DCT may be considered a suitable treatment option for mCRPC patients recurring after a successful DCT chemotherapy. The interest in this strategy may be increased because of the showed efficacy of early DCT chemotherapy in patients with bulky disease (CHAARTED study) and the potential lower efficacy of the new hormonal agents abiraterone acetate and enzalutamide when used in a immediate sequencing.
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The primary objective of this trial was to establish the maximum tolerated dose (MTD) of oxaliplatin 130 mg/m2 preceded by escalating doses of docetaxel 60 mg/m2 (75, 90, 100 mg/m2) administered every 3 weeks. A total of 11 patien...
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The primary objective of this trial was to establish the maximum tolerated dose (MTD) of oxaliplatin 130 mg/m2 preceded by escalating doses of docetaxel 60 mg/m2 (75, 90, 100 mg/m2) administered every 3 weeks. A total of 11 patients were entered; 10 evaluable for response: 4 stable disease (liver, ovary and esophagus) and 1 partial remission (esophagus). At dose level 1, there was 1 dose-limiting toxicity (DLT) (grade 3 allergic reaction). At dose level 2, there were 3 DLTs (3 grade 4 neutropenia, grade 3 gastritis, diarrhea, hypophosphatemia, neuro-mood). The MTD is docetaxel 60 mg/m2 with oxaliplatin 130 mg/m2.
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BACKGROUND: In a phase III trial, 3-weekly capecitabine (1250 mg/m(2) twice daily days 1-14) plus docetaxel (75 mg/m(2) day 1) demonstrated significantly superior overall survival to 3-weekly docetaxel (100 mg/m(2) day 1). We repo...
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BACKGROUND: In a phase III trial, 3-weekly capecitabine (1250 mg/m(2) twice daily days 1-14) plus docetaxel (75 mg/m(2) day 1) demonstrated significantly superior overall survival to 3-weekly docetaxel (100 mg/m(2) day 1). We report a retrospective analysis of the impact of capecitabine/docetaxel dose reduction on safety and efficacy. PATIENTS AND METHODS: Safety and efficacy data were analyzed retrospectively according to the actual doses of capecitabine and docetaxel administered. RESULTS: More patients receiving capecitabine/docetaxel (65%) had dose reductions for adverse events than docetaxel alone (35%). In most patients requiring dose reduction with the combination (80%), capecitabine and docetaxel were simultaneously reduced to 950 mg/m(2) and 55 mg/m(2), respectively. Subsequently, there were fewer cycles (17%) with grade 3/4 adverse events than with the full doses (34%). Time to progression and overall survival appeared to be similar in patients starting the second cycle with reduced doses of capecitabine/docetaxel and those who continued to receive full doses of capecitabine/docetaxel for at least the first four cycles. CONCLUSIONS: Capecitabine/docetaxel dosing flexibility allows management of side-effects without compromising efficacy. This retrospective analysis, as well as multiple phase II studies of taxanes with reduced-dose capecitabine, shows that reducing the starting dose of capecitabine with docetaxel is a reasonable strategy for the treatment of patients with metastatic breast cancer. In addition, reducing the dose of both agents may be appropriate.
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"Letter to the Editor: "Docetaxel and its nanoformulations: how delivery strategies could impact the therapeutic outcome?”." Therapeutic Delivery, 12(5), pp. 343–344.
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Introduction: Two solid dispersions of docetaxel (denoted ModraDoc001 capsule and ModraDoc006 tablet (both 10 mg)) were co-administered with 100 mg ritonavir (/r) and investigated in a bi-daily once weekly (BIDW) schedule. Safety,...
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Introduction: Two solid dispersions of docetaxel (denoted ModraDoc001 capsule and ModraDoc006 tablet (both 10 mg)) were co-administered with 100 mg ritonavir (/r) and investigated in a bi-daily once weekly (BIDW) schedule. Safety, maximum tolerated dose (MTD), pharmacokinetics (PK) and preliminary activity were explored.
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A new HPLC method has been developed for the quantitative determination of methotrexate (MTX) and its 7-hydroxyl metabolite in human plasma. Samples were purified by protein precipitation with acetone and methanol, and a sample cl...
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A new HPLC method has been developed for the quantitative determination of methotrexate (MTX) and its 7-hydroxyl metabolite in human plasma. Samples were purified by protein precipitation with acetone and methanol, and a sample clean-up with a mixture of n-butanol and diethyl ether. The analytes were separated on an RP Inertsil ODS-80A column and eluted in a solvent system containing 5% (v/v) tetrahydrofuran in water (pH 2.0).UV absorption measurement was performed at 313 nm,and the detector response was linear in a concentration range of 10-10 000 ng/ml. The lower limit of quantitation of MTX was 10 ng/ml using 1 ml sample aliquots. Values for accuracy and (within-run and between-run) precision were between 95.5-11% and 3.69-11.0%,respectively,at four concentrations analyzed in quintuplicate on four separate occasions. The assay was applied to study the effects of docetaxel co-administration on the pharmacokinetics and metabolism of MTX in cancer parients.
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