Open-label, randomized study of individualized, pharmacokinetically (PK)-guided dosing of paclitaxel combined with carboplatin or cisplatin in patients with advanced non-small-cell lung cancer (NSCLC).
Journal article

Open-label, randomized study of individualized, pharmacokinetically (PK)-guided dosing of paclitaxel combined with carboplatin or cisplatin in patients with advanced non-small-cell lung cancer (NSCLC).

  • Joerger M Department of Medical Oncology, Cantonal Hospital, St Gallen, Switzerland markus.joerger@kssg.ch.
  • von Pawel J Pneumology Clinic, Asklepios Fachkliniken, Gauting.
  • Kraff S Institute of Pharmacy, Clinical Pharmacy, University of Bonn, Bonn.
  • Fischer JR Department of Medical Oncology, Klinik Löwenstein, Löwenstein.
  • Eberhardt W Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen.
  • Gauler TC Department of Medical Oncology (Cancer Research), West German Cancer Center, University Hospital Essen of University Duisburg-Essen, Essen.
  • Mueller L Oncological Practice, Praxis Leer, Leer.
  • Reinmuth N Lung Clinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf.
  • Reck M Lung Clinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf.
  • Kimmich M Pulmonology and Oncology, Klinik Schillerhöhe, Gerlingen.
  • Mayer F Department of Oncology and Hematology, University Hospital, Medical Center II, Tübingen.
  • Kopp HG Department of Oncology and Hematology, Eberhard Karls University Medical Center, Tübingen.
  • Behringer DM Medical Oncology, Augusta-Kranken-Anstalt, Bochum.
  • Ko YD Medical Oncology, Johanniter-Krankenhaus Bonn, Bonn.
  • Hilger RA Cancer Research, University Hospital Essen, Essen, Germany.
  • Roessler M CESAR Central Office (CCO), Vienna CESAR Central European Society for Anticancer Drug Research-EWIV, Vienna, Austria.
  • Kloft C Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Free University Berlin, Berlin, Germany.
  • Henrich A Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Free University Berlin, Berlin, Germany.
  • Moritz B CESAR Central Office (CCO), Vienna CESAR Central European Society for Anticancer Drug Research-EWIV, Vienna, Austria.
  • Miller MC Saladax Biomedical, Inc., Bethlehem, USA.
  • Salamone SJ Saladax Biomedical, Inc., Bethlehem, USA.
  • Jaehde U Institute of Pharmacy, Clinical Pharmacy, University of Bonn, Bonn.
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  • 2016-08-10
Published in:
  • Annals of oncology : official journal of the European Society for Medical Oncology. - 2016
English BACKGROUND
Variable chemotherapy exposure may cause toxicity or lack of efficacy. This study was initiated to validate pharmacokinetically (PK)-guided paclitaxel dosing in patients with advanced non-small-cell lung cancer (NSCLC) to avoid supra- or subtherapeutic exposure.


PATIENTS AND METHODS
Patients with newly diagnosed, advanced NSCLC were randomly assigned to receive up to 6 cycles of 3-weekly carboplatin AUC 6 or cisplatin 80 mg/m(2) either with standard paclitaxel at 200 mg/m(2) (arm A) or PK-guided dosing of paclitaxel (arm B). In arm B, initial paclitaxel dose was adjusted to body surface area, age, sex, and subsequent doses were guided by neutropenia and previous-cycle paclitaxel exposure [time above a plasma concentration of 0.05 µM (Tc>0.05)] determined from a single blood sample on day 2. The primary end point was grade 4 neutropenia; secondary end points included neuropathy, radiological response, progression-free survival (PFS) and overall survival (OS).


RESULTS
Among 365 patients randomly assigned, grade 4 neutropenia was similar in both arms (19% versus 16%; P = 0.10). Neuropathy grade ≥2 (38% versus 23%, P < 0.001) and grade ≥3 (9% versus 2%, P < 0.001) was significantly lower in arm B, independent of the platinum drug used. The median final paclitaxel dose was significantly lower in arm B (199 versus 150 mg/m(2), P < 0.001). Response rate was similar in arms A and B (31% versus 27%, P = 0.405), as was adjusted median PFS [5.5 versus 4.9 months, hazard ratio (HR) 1.16, 95% confidence interval (CI) 0.91-1.49, P = 0.228] and OS (10.1 versus 9.5 months, HR 1.05, 95% CI 0.81-1.37, P = 0.682).


CONCLUSION
PK-guided dosing of paclitaxel does not improve severe neutropenia, but reduces paclitaxel-associated neuropathy and thereby improves the benefit-risk profile in patients with advanced NSCLC.


CLINICAL TRIAL INFORMATION
NCT01326767 (https://clinicaltrials.gov/ct2/show/NCT01326767).
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://sonar.ch/global/documents/159113
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