Article

Clinical and pharmacokinetics study of oxaliplatin in colon cancer patients.

Department of Immunology, University of Medicine and Pharmacy Iuliu Hatieganu, Romania.
Journal of gastrointestinal and liver diseases: JGLD (Impact Factor: 1.85). 04/2009; 18(1):39-43.
Source: PubMed

ABSTRACT to evaluate the therapeutic efficacy of oxaliplatin and to analyze the pharmacokinetics of both ultrafiltrable (free) and protein-bound platinum in patients with metastatic colon cancer.
60 patients with stage IV colon carcinoma received 4-6 (mean 4.5) cycles of oxaliplatin based combination chemotherapy. Response rate, progression-free survival (PFS) and toxicity were evaluated. The pharmacokinetics of oxaliplatin was evaluated in 8 patients who were given 85 mg/sqm or 130 mg/sqm using an infusion time of 2-4 h. Pharmacokinetic analysis was performed on blood, plasma and plasma ultrafiltrable by ICP-MS (Inductively Coupled Plasma Mass Spectrometry).
Overall response rate (complete and partial) occurred in 33 (55%) patients. The median time of progression was 9.3 months. Cumulative neurotoxicity, vomiting and diarrhea, myelosuppression appeared in 32.3%, 21.3%, and 39.4% patients, respectively. The mean Cmax and AUC 0-24 of oxaliplatin increased in a dose-related manner. The pharmacokinetics of platinum after oxaliplatin administration was triphasic characterized by a short initial distribution phase and a long terminal elimination phase.The clearance of ultrafiltrable platinum was relatively high and the clearance of platinum from plasma and blood cells was relatively low, which is probably a reflection of the covalent binding of platinum to these matrices.
Oxaliplatin is active and well tolerated in patients with advanced colon cancer. With a relatively low interpatient variability, it is eliminated triphasically and the mean Cmax and AUC 0-24 increases in a dose-related manner. These results provide a scientific basis for the safe and effective use of oxaliplatin in the clinic.

Full-text

Available from: Sorin Leucuta, Jun 10, 2015
0 Followers
 · 
187 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE: Vismodegib, a Hedgehog pathway inhibitor, has preclinical activity in colorectal cancer (CRC) models. This trial assessed the efficacy, safety, and pharmacokinetics of adding vismodegib to first-line treatment for metastatic CRC (mCRC). Experimental design: Patients were randomized to receive vismodegib (150 mg/day orally) or placebo, in combination with FOLFOX or FOLFIRI chemotherapy plus bevacizumab (5 mg/kg) every 2 weeks until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). Key secondary objectives included evaluation of predictive biomarkers and pharmacokinetic drug interactions. RESULTS: A total of 199 patients with mCRC were treated on protocol (124 FOLFOX, 75 FOLFIRI). The median PFS hazard ratio for vismodegib treatment compared with placebo was 1.25 (90% CI: 0.89-1.76; P = 0.28). The overall response rates for placebo-treated and vismodegib-treated patients were 51% (90% CI: 43-60) and 46% (90% CI: 37-55), respectively. No vismodegib-associated benefit was observed in combination with either FOLFOX or FOLFIRI. Increased tumor tissue Hedgehog expression did not predict clinical benefit. Grade 3-5 adverse events reported for >5% of patients that occurred more frequently in the vismodegib-treated group were fatigue, nausea, asthenia, mucositis, peripheral sensory neuropathy, weight loss, decreased appetite, and dehydration. Vismodegib did not alter the pharmacokinetics of FOLFOX, FOLFIRI, or bevacizumab. CONCLUSIONS: Vismodegib does not add to the efficacy of standard therapy for mCRC. Compared with placebo, treatment intensity was lower for all regimen components in vismodegib-treated patients, suggesting that combined toxicity may have contributed to lack of efficacy.
    Clinical Cancer Research 10/2012; 19(1). DOI:10.1158/1078-0432.CCR-12-1800 · 8.19 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Individual responses to oxaliplatin (L-OHP)-based chemotherapy remain unpredictable. Our recent proteomics studies have demonstrated that intracellular protein expression levels of S100A10 are significantly correlated with the sensitivity of colorectal cancer (CRC) cells to L-OHP, but not 5-FU, suggesting that S100A10 is a candidate predictive marker for the response to L-OHP. In this study, we investigated whether S100A10 is involved in L-OHP sensitivity or not.
    Proteome Science 05/2014; 12:26. DOI:10.1186/1477-5956-12-26 · 1.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This paper describes a model reference adaptive system (MRAS) for the speed estimation of induction motor from measured terminal voltages and currents. The estimated speed is used as feedback in a vector control system. The MRAS approach has the immediate advantage in that the model is simple, very easy to implement and has direct physical interpretation. This paper studies the influence of the stator resistance variation on MRAS speed estimation. It has been shown that when a motor is running at high speed, the effect of error in stator resistance is usually quite negligible. But as the frequency approaches zero, this becomes more serious because the voltage drop on stator resistance becomes relatively larger as the frequency decreases. In comparison with rotor resistance adaptation, the stator resistance adaptation has received less consideration. In this paper, a new reference scheme has been used for stator resistance estimation. Under this reference scheme, one component of flux can be decoupled from the corrupting effects of the stator resistance and the other quadrature component can provide a near-instantaneous estimate of the stator resistance. In the system, the output of the stator resistance identifier updates the value of the stator resistance used in the MRAS speed estimator. Simulation of rotor field oriented speed sensorless control of VSI-fed induction motor using stator circuit variables is performed incorporating the on-line stator resistance estimation technology.
    Power Electronic Drives and Energy Systems for Industrial Growth, 1998. Proceedings. 1998 International Conference on; 01/1999