Defining an Exposure Target for Weekly Paclitaxel Infusion in Breast Cancer Patients

Paclitaxel is a chemotherapeutic agent commonly used in various tumor types. Paclitaxel
efficacy and toxicity are "dose-dependent" meaning that increasing the dose increases
treatment efficacy and occurrence of toxicity. When used in the weekly 1-hour infusion
regimen paclitaxel is commonly associated with treatment-limiting sensory peripheral
neuropathy. At the current standard dose of 80 mg/m2 approximately 20-25% of patients
experience treatment-limiting neuropathy.

Drug exposure, not dose, determines treatment efficacy and neuropathy development. When
treated with standard doses there is substantial variability in drug exposure meaning some
patients are receiving less efficacious treatment than optimal. At this time we do not
monitor a patient's exposure because the optimal exposure level has not been defined. The
purpose of this study is to prospectively enroll patients for systematic collection of
exposure and neuropathy data in order to characterize this relationship. Once the
relationship between cumulative exposure and neuropathy has been characterized, this model
will be used to define an exposure target in future prospective exposure-guided
dose-adjustment trials.

Inclusion Criteria:

- Diagnosis of invasive breast cancer

- Systemic treatment with paclitaxel for curative intent (neoadjuvant, adjuvant, or
oligometastatic disease per PI discretion)

- 80 mg/m2 1-hour infusions weekly for up to 12 weeks

- Female sex

->18 years old

- Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

- Any prior or concurrent treatment with neurotoxic chemotherapy including any taxane,
vinca alkaloid, platinum, bortezomib, or thalidomide. Note that concurrent biologic
treatment with trastuzumab/pertuzumab for HER2+ patients or prior treatment with
Adriamycin/cyclophosphamide are not reasons for exclusion.

- Distant metastatic disease

- Concurrent treatment with duloxetine or enrollment on clinical study of
neuroprotective agent

- History of allergic reaction to paclitaxel or cremophor EL

- Current signs or symptoms of severe peripheral neuropathy

- Known family history of hereditary peripheral neuropathy or Charcot-Marie-Tooth
disease

- Known current pregnancy