Female patients >18 years old diagnosed with stage I-III or oligometastatic breast cancer receiving treatment at the University of Michigan Comprehensive Cancer Center (UMCCC) who were scheduled to receive 12 weekly doses of 80 mg/m2 paclitaxel infused over 1 hour, as per decision with their medical oncologist, were eligible for this observational clinical trial (NCT02338115). Patients were excluded if they received any prior treatment with a neurotoxic chemotherapeutic agent (i.e., taxanes, vinca alkoloids, bortezomib), had existing neuropathy that interfered with activities of daily living, had a known history of hereditary neuropathy including Charcot-Marie-Tooth disease, or were receiving treatment with duloxetine or enrolled in a clinical trial of an agent for neuropathy protection or treatment. Enrolled subjects who withdrew from the study or discontinued paclitaxel treatment for any reason prior to receiving five paclitaxel doses were excluded from analyses and replaced. All patients signed written informed consent and the study was approved by the University of Michigan IRBMed and conducted in accordance with recognized ethical guidelines including the Declaration of Helsinki and Belmont Report.
Eligible patients were enrolled into the observational clinical trial prior to their first dose of paclitaxel. The morning of their first infusion, prior to treatment, patients completed a baseline survey that collected demographic information (i.e. age, self-reported race) and neuropathy-relevant medical information such as diagnosis of diabetes mellitus (self-reported), current alcohol consumption (no or yes [and approximate number of drinks per week]), and pain medications taken regularly. Prior to treatment, blood samples were collected for future pharmacogenetic and pharmacometabolomic analyses and measurement of neuropathy-associated nutrients including hemoglobin A1c (HbA1c), vitamins B12 and D, homocysteine, and folate.
Paclitaxel doses and dates of dosing were prospectively entered into Michart, the medical record used within UMCCC, as standard clinical practice and then retrospectively abstracted by a study coordinator blinded to all other data. Actual dosing information was collected and used to quantify the relative dose intensity, defined by the amount of paclitaxel administered relative to the proportion of the planned cumulative dose. All instances of decreases in the weekly paclitaxel dose (≥10 % in mg/m2), delays between paclitaxel doses (≥ 13 days between doses), or discontinuations of paclitaxel treatment, collectively referred to as treatment disruptions, were documented in the study database. The cause of treatment disruption (neuropathy, other toxicity, scheduling, patient request, other/unknown) was determined by the blinded study coordinator based on manual review of MiChart relying primarily on the clinical notes written at each treatment visit (typically just prior to infusion on treatment weeks 4, 7, and 10). The study coordinator also reviewed all e-mail correspondence and summaries of telephonic communications between the patient and their care team or UMCCC nursing staff, all of which is documented within MiChart.
Eligible patients were enrolled into the observational clinical trial prior to their first dose of paclitaxel. The morning of their first infusion, prior to treatment, patients completed a baseline survey that collected demographic information (i.e. age, self-reported race) and neuropathy-relevant medical information such as diagnosis of diabetes mellitus (self-reported), current alcohol consumption (no or yes [and approximate number of drinks per week]), and pain medications taken regularly. Prior to treatment, blood samples were collected for future pharmacogenetic and pharmacometabolomic analyses and measurement of neuropathy-associated nutrients including hemoglobin A1c (HbA1c), vitamins B12 and D, homocysteine, and folate.
Paclitaxel doses and dates of dosing were prospectively entered into Michart, the medical record used within UMCCC, as standard clinical practice and then retrospectively abstracted by a study coordinator blinded to all other data. Actual dosing information was collected and used to quantify the relative dose intensity, defined by the amount of paclitaxel administered relative to the proportion of the planned cumulative dose. All instances of decreases in the weekly paclitaxel dose (≥10 % in mg/m2), delays between paclitaxel doses (≥ 13 days between doses), or discontinuations of paclitaxel treatment, collectively referred to as treatment disruptions, were documented in the study database. The cause of treatment disruption (neuropathy, other toxicity, scheduling, patient request, other/unknown) was determined by the blinded study coordinator based on manual review of MiChart relying primarily on the clinical notes written at each treatment visit (typically just prior to infusion on treatment weeks 4, 7, and 10). The study coordinator also reviewed all e-mail correspondence and summaries of telephonic communications between the patient and their care team or UMCCC nursing staff, all of which is documented within MiChart.
