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
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.
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).
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).