Impact of Body Weight on Pharmacokinetic Analysis of Doxorubicin + Cyclophosphamide in Breast Cancer

The study will require a total of 11 participant contacts over 3 days (1 day outpatient
clinic visit for doxorubicin and cyclophosphamide infusions and blood draws, 2 follow up
outpatient clinic visits for blood draws) with no more than 100 mL of blood being drawn. All
blood draws will be collected for the purpose of research.

Screening and Informed Consent Procedures

1. The participant's height, weight, medical history, comorbid conditions, and current
medications will be obtained from the electronic medical record (EMR).

Update 1 : January 12, 2012

2. Study personnel will provide the participant with additional information about the study
and provide the participant with the opportunity to ask any questions. Each participant
will then be asked if she is willing to provide informed consent.

3. Information from the routine physical examination including vital signs
(temperature,respiratory rate, blood pressure, heart rate) will be collected from the
medical chart.

Procedures and Evaluation during the Research

1. Each participant will then have no more than10ml of blood drawn 8 times, at t=0h
(predose),at the end of the doxorubicin infusion, at the end cyclophosphamide infusion,
and 1.5, 2, 3, 4, 5, 12-24, and 24-72 h following the beginning of doxorubicin infusion.
All blood draws will be performed using the peripheral intravenous catheter being used
for standard medical care. Labels on blood samples will not contain participant name,
but a randomly generated participant identification number.

2. All blood samples will placed on ice and immediately transported to Dr. Richard Leff's
laboratory for sample preparation.9 Samples will be spun in a refrigerated centrifuge
and then placed in a -80oC freezer. As explained below, Dr. Leff or his laboratory will
not have access to any participant identifiers.

3. The participant is discharged from the cancer center (for research purposes) after the 4
hour blood draw, unless the participant is willing to stay for the 5 hour blood draw.

4. The participant will return to the cancer center at 12-24 and 24-72 hours for blood
draws.

5. The participant is discharged from the study after the 24-72h blood draw. Follow-up:
Participants will be asked to return to the cancer center for 12-24 and 24-72 hour blood
draws.

Inclusion Criteria:

- Females,

- age 18 years of age or older, of all racial and ethnic origins that are scheduled to
receive the first cycle of a single intravenous dose of doxorubicin (30 minute
infusion) and cyclophosphamide (30 minute infusion) as part of standard medical care
for breast cancer.

- English and/or Spanish speaking participants are eligible to participate.

Exclusion Criteria:

- Pregnant or nursing or unwilling to use a reliable contraception method during the
study. The effects of doxorubicin and cyclophosphamide on pregnancy are unknown. In
addition, the metabolic changes that accompany pregnancy may alter the
concentration-time profile of doxorubicin or cyclophosphamide, so that the pregnancy
and post-partum state would be a confounding variable.

- Participants unwilling to comply with study procedures.

- CrCl < 10 ml/min

- Participants requiring peritoneal or hemodialysis

- Serum bilirubin > 1.19 mg/dL

- Receipt of the following drugs that:

- Alter doxorubicin concentrations: carbamazepine, cyclosporine, fosphenytoin,
paclitaxel, phenytoin, sorafenib, valspodar, verapamil

- Alter cyclophosphamide concentrations: cyclosporine, nevirapine, ondansetron

- All other drugs will be reviewed during screening of the patient