Docetaxel, Carboplatin, and Capecitabine as Treatment for Patients With Locally Advanced or Inflammatory Breast Cancer Before Surgery
Docetaxel, Carboplatin, and Capecitabine as Treatment for Patients With Locally Advanced or Inflammatory Breast Cancer Before Surgery
The purpose of this study is to determine if this combination is safe and effective in this
 situation especially to increase the rate of pathological complete response (PCR). Women with
 large tumors and or lymph node involvement at the time of initial diagnosis may benefit from
 receiving chemotherapy prior to surgery to shrink the tumor and to decrease the amount of
 tumor involvement before surgery. If chemotherapy given before breast surgery is effective in
 decreasing the size of the tumor, breast conserving surgery (lumpectomy) may be possible.
 This new combination may be better tolerated than other commonly used regimens and, to date,
 appears to be at least as effective.
Neoadjuvant (primary) chemotherapy is being used more frequently in locally advanced breast
 cancer in an effort to reduce the size of the primary tumor prior to surgery and to eliminate
 micrometastatic disease.Through previous studies, it has been shown that patients who receive
 neoadjuvant therapy demonstrate prolonged disease-free survival when compared to those who
 did not have a pCR at the time of surgery.

 It is proven that docetaxel is the single most active drug in metastatic breast cancer
 treatment and therefore has sparked interest in its use in the neoadjuvant setting. There
 have been studies conducted using docetaxel either alone or in combination in this setting
 and in one particular study showed that patients treated with docetaxel after an
 anthracycline -containing regimen achieved at 34% pCR compared to only 16% with the
 anthracycline-containing regimen alone. This drugs low incidence of neutropenia when
 administered on a weekly schedule, plus its possible synergistic effects with carboplatin and
 capecitabine lead to its inclusion in this neoadjuvant protocol.

 Carboplatin is an agent that has recently been integrated into the front line of breast
 cancer treatment due to its response rate and tolerability. This drug as well has warranted
 further investigation in the neoadjuvant setting and was combined with docetaxel in one trial
 for for locally advanced disease which showed a preliminary pCR of the breast and axilla of
 30% and 80% respectively. Due to its tolerability, minimal toxicities, and impressive results
 as a single agent and in combination with docetaxel made carboplatin a reasonable drug of
 choice in this study.

 The novel oral agent capecitabine is being used in this protocol because it has shown through
 study to significantly increase response rate, time to progression, and even overall survival
 when combined with docetaxel in the metastatic setting. As well, capecitabine behaves
 similarly to continuous 5-FU infusion which has shown success in several phase II neoadjuvant
 trials and essentially has led to its inclusion in this study. Capecitabine's anti-tumor
 activity, coupled with ease of administration, potential synergism with docetaxel and
 carboplatin, and non-overlapping toxicities justifies its inclusion in this investigational
 regimen.
Inclusion Criteria:

 -  Women or men > 18 years old with histologically confirmed, by needle core biopsy (not
 FNA), locally advanced or inflammatory breast cancer.

 -  All patients must have either T2 lesion which is felt to be initially resectable only
 through mastectomy by the surgeon, or with a T3 N0-N2; T4 any N; or any T with N2 or
 N3 clinical evidence of disease. Stage 2 patients where breast conservation surgery is
 desired but impractical at diagnosis because of anticipated poor cosmetic outcome are
 eligible. Patients with inflammatory breast carcinoma and women with ipsilateral
 supraclavicular node involvement are eligible. Patients must have measurable disease
 defined as a breast lesion > 2 cm or with fixed or marked ipsilateral axillary nodes
 and/or ipsilateral internal mammary nodes.

 -  Pre-and Post-menopausal female and male patients are eligible. Women of childbearing
 potential must have a negative pregnancy test and, men and women must be willing to
 consent to using effective dual methods of contraception while on treatment and for
 three months thereafter.

 -  Life expectancy of greater than 6 months.

 -  Bone scan and CAT scan of chest and abdomen negative for metastatic disease

 Exclusion Criteria:

 -  Patients with metastatic disease.

 -  Patients may not be receiving any other investigational agents.

 -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
 infection other than mild resolving cellulitis, symptomatic congestive heart failure
 (NYHA > Class 1), unstable angina pectoris, uncontrolled cardiac arrhythmia, known
 coronary artery disease, or psychiatric illness/social situations that would limit
 compliance with study requirements.

 -  Cancer other than breast primary within the last 5 years with the exception of
 surgically cured non-melanoma skin cancer or in situ carcinoma of the cervix.

 -  Women who are breast-feeding.