Reduced Toxicity By Controlling Exposure

Docetaxel is predominantly used to treat breast cancer, but is also an important component in non-small cell lung, digestive tract, prostate and head & neck cancer treatment regimens. Just as with paclitaxel, many patients suffer severe dose-limiting toxicities on docetaxel.¹ As you can see below, many patients suffer neutropenia or febrile neutropenia, a susceptibility to bacterial infections. Leukopenia, also associated with reduced white blood cell count, can cause serious symptoms such as anemia, fatigue, headaches, disturbed emotional balance, inflammation of the mucous lining of the mouth and pneumonia. Severe infections can be life threatening and a significant percentage of docetaxel patients are at risk.

The interpatient plasma level variability of docetaxel is high when the drug is administered based on BSA. Patients receiving BSA-based docetaxel can show greater than 7-fold variability in clearance rates. This was demonstrated in six different treatment regimens that incorporate docetaxel.²

Overexposure of docetaxel has been demonstrated to correlate with a reduced neutrophil count, which can cause the serious side effects discussed above.³

Incidence and higher degree of neutropenia are associated with higher docetaxel systemic exposure.⁴

In a study of 640 patients, docetaxel clearance was found to be a strong predictor of grade
4 (the most severe) and febrile neutropenia. A 50% reduction in docetaxel clearance led to a 4-fold increase in grade 4 neutropenia and a 3-fold increase in febrile neutropenia.⁵

MyDocetaxel enables oncologists to identify docetaxel-treated patients at high risk of developing severe toxicity by measuring their systemic drug exposure. Armed with this information, physicians can reduce their patient’s docetaxel dose or prophylactically administer granulocyte colony-stimulating factor (GCSF).

Docetaxel dose management with MyDocetaxel is simple. Two blood samples are drawn – the first five minutes before the end of drug infusion and the second one hour after the end of infusion⁶. Upon analysis by a clinical laboratory, an individualized report is generated and returned to your doctor in time to make therapeutic adjustments for the next cycle of treatment. The critical pharmacokinetic parameter for docetaxel is Area Under the Curve (AUC), the overall amount of drug in the bloodstream after a dose. The MyDocetaxel test result, together with the professional clinical experience and medical knowledge of your doctor, will be the basis for the decision on dose adjustment. Monitoring patients’ systemic docetaxel levels helps control toxicity throughout the course of treatment, preventing premature treatment discontinuation due to dose-limiting toxicities.

REFERENCES

1. TAXOTERE® package insert.
2. Rudek, MA, et al., Eur J Cancer, 40:1170-1178, 2004.
3. Extra, et al., Cancer Res, 53:1037-1042, 1993.
4. Ten Tije, et al., J Clin Oncol, 23:1070-1077, 2005.
5. Bruno, et al., J Clin Oncol, 16:187-196, 1998.