Paclitaxel 

Neutropenia and neuropathy can be serious side-effects associated with paclitaxel chemotherapy.  While hematological toxicities can be addressed, there is no good solution for chemotherapy induced peripheral neuropathy, which is frequent, may be debilitating and can persist or appear after treatment. 

  • One of the largest randomized TDM studies ever demonstrated the  potential of paclitaxel dose optimization to:
    • Reduce neuropathy, 
    • Reduce neutropenia,
    • Without impacting survival
 
 

Publications of Interest

 
Ann Oncol. 2016 Oct 27(10):1895-1902 

Ann Oncol. 2016 Oct 27(10):1895-1902 

Open-label, randomized study of individualized, pharmacokinetically (PK)-guided dosing of paclitaxel combined with carboplatin in advanced Non-Small Cell Lung Cancer (NSCLC) patients.

This study was one of the largest studies (n=304) ever done for therapeutic dose management compared to dosing by BSA.   In the PK-guided arm patient’s doses were adjusted according to their drug level (pharmacokinetic parameter was time above threshold concentration Tc>0.05) from the previous cycle.  PK guided dosing significantly reduced grade 4 neutropenia (29%), and grades of neutropenia ≥2 (48%) and ≥3 (88%).  Survival was similar in both arms.  Patients whose doses were adjusted with TDM had an improved risk-benefit profile.

https://www.ncbi.nlm.nih.gov/pubmed/27502710

 
Clin Cancer Res. 2007 Nov 1;13(21):6410-8

Clin Cancer Res. 2007 Nov 1;13(21):6410-8

Population pharmacokinetics and pharmacodynamics of paclitaxel and carboplatin in ovarian cancer patients: a study by the European organization for research and treatment of cancer-pharmacology and molecular mechanisms group and new drug development group

This study demonstrated concentration-effect relationships of paclitaxel for both toxicity and outcome in 103 ovarian cancer patients.   The relevant pharmacokinetic parameter was time above threshold Tc>0.05. Patients with severe neutropenia (grade 3 – 4) had higher paclitaxel exposure than patients with mild or absent neutropenia (p=0.02). Remission and stable disease compared to progressive disease were both associated with paclitaxel levels (p=0.02 and p=0.05).  Patients with higher paclitaxel also had longer time to progression (p=0.03).
http://clincancerres.aacrjournals.org/content/13/21/6410.long

 

Anticancer Res. 2005 Nov-Dec; 25(6C): 4423-7

Anticancer Res. 2005 Nov-Dec; 25(6C): 4423-7

Paclitaxel pharmacokinetics and response to chemotherapy in patients with advanced cancer treated with a weekly regimen

This studied followed others in observing that paclitaxel pharmacokinetics (time above a threshold concentration Tc>0.05) was associated with pharmacodynamic effect. In patients with heterogeneous tumor types (n=29) these investigators found paclitaxel exposure influenced both toxicity and outcome. In addition, patients with partial responses or stable disease had higher paclitaxel exposure than patients with progressive disease (p=0.039).  In a separate publication from the same study, patients who developed peripheral neuropathy also had significantly higher paclitaxel levels (Tc>0.05, p=0.22).

http://ar.iiarjournals.org/content/25/6C/4423.long

 
 
 
Current Chemo Dosing Practices

Current Chemo Dosing Practices