Evaluation of Differing Taxanes/Taxane Combinations on the Outcome of Patients With Operable Breast Cancer
Evaluation of Differing Taxanes/Taxane Combinations on the Outcome of Patients With Operable Breast Cancer
Primary Objectives:

 -  Determine the impact of each regimen on the disease free and overall survival of
 patients with operable breast cancer.

 -  Determine the ability of docetaxel/capecitabine to downstage primary breast cancer when
 administered in the neoadjuvant setting when compared with weekly paclitaxel.

 -  Determine the ability of each regimen to enhance breast conservation therapy when
 administered in the neoadjuvant setting. (See protocol text for additional objectives
 and details).
Before the study, participants will have a complete physical exam, including blood tests and
 a chest x-ray. A mammogram and a sonogram of the breast and armpit will be done to record
 tumor size (for patients who have not had surgery). Sonography of the liver or a CT scan of
 the abdomen will also be done. In some patients who have not had surgery, 3-4 samples of the
 breast tumor will be taken to help confirm the diagnosis of breast cancer. A biopsy needle
 will be used to collect the samples.

 During the study, participants will have blood tests done before each dose of chemotherapy.
 For participants who have not had surgery, a mammogram and sonogram will be done of the
 breast and armpit after completion of paclitaxel or docetaxel/capecitabine and after
 completion of fluorouracil, cyclophosphamide, and epirubicin (FEC). These studies will help
 doctors to keep track of the tumor size and help with the final decision whether to remove
 all or part of the breast and nearby lymph nodes after completion of chemotherapy.

 Participants in this study will be randomly assigned (as in the toss of a coin) to one of two
 treatment groups. There is an equal chance of being in either group.

 Participants in Group I will receive paclitaxel once a week. The drug will be given through a
 plastic tube in a vein over 1 hour for a total of 12 treatments. Before each treatment,
 patients will receive the drug Decadron (dexamethasone) through the vein and may receive
 Zofran (ondansetron), Benadryl (diphenhydramine hydrochloride) and/or cimetidine to help
 decrease the risk of side effects from paclitaxel.

 Participants in Group II will receive docetaxel and capecitabine. Docetaxel will be given
 once every 3 weeks. Docetaxel will be given through a plastic tube in the vein over 1 hour.
 Capecitabine will be started the same day docetaxel is given. This medicine is given in a
 pill form. The doctor will prescribe a dose of these pills based upon body weight and height.
 Participants will take several pills two times a day for 14 days. Participants will then not
 take any capecitabine pills for one week, until the next dose of docetaxel is given. This
 combination of docetaxel and capecitabine will be given four times (over a period of 12
 weeks). Before each treatment, patients will receive the drug Decadron (dexamethasone) by
 mouth.

 After treatment with either paclitaxel or docetaxel/capecitabine, all participants will
 receive the drugs FEC through a plastic tube into a vein. All of these drugs will be given
 once every three weeks for a total of 4 treatments (12 weeks total). Decadron
 (dexamethasone), Zofran (ondansetron) and Benadryl (diphenhydramine hydrochloride) will be
 given before the chemotherapy to help decrease the risk of side effects.

 Participants who have a Her-2/neu positive cancer will potentially be eligible to receive
 trastuzumab therapy for 1 year. This medicine is given through a vein either once a week
 (over 30 minutes) or once every 3 weeks (over 30 minutes). Your doctor will discuss whether
 this medicine is appropriate for you.

 After all treatment is done, participants whose tumors are sensitive to hormones (estrogen)
 will take a pill to help decrease the amount of hormone (estrogen) that can reach any tumor
 cells. This pill will be taken once a day for 5 years.

 Participants who have not completed surgery for their cancer before receiving the
 chemotherapy described above will have surgery to remove all or part of the breast that has
 cancer. If there are signs that the lymph nodes in the armpit (axilla) contain cancer, these
 lymph nodes will also be removed.

 After chemotherapy and surgery, or after completion of chemotherapy (patients who had surgery
 done first), participants may then receive radiation treatment to the breast area and armpit
 once a day (Monday through Friday) for 5-6 weeks.

 After the study, participants will return for checkups every 3-4 months during Years 1 and 2,
 every 6 months during years 3 and 4 and yearly after that. During the check-ups participants
 will talk with and be examined by their physician. Once a year, patients will have yearly
 mammograms (as needed), chest-x rays, and blood tests.

 This is an investigational study. All of the drugs in this study are approved by the FDA for
 treatment of breast cancer. A total of 930 patients will take part in this study. All will be
 enrolled at M. D. Anderson.
Inclusion Criteria:

 1. Patients with histologic confirmation of invasive, but non-inflammatory carcinoma of
 the breast.

 2. Stage I (T1N0) are not eligible for the neo-adjuvant portion of the protocol.

 3. High-risk patients (patients with any of the following: high proliferation rate - Ki67
 >35% or poorly differentiated tumors (black's modified grade 3); ER/PR negative;
 lymphovascular invasion) with stage I disease are eligible for adjuvant therapy.

 4. Patients with pure mucinous carcinomas, tubular carcinomas or pure medullary
 carcinomas are eligible if the patient's tumor is larger than 3 cm in size or if the
 patient has tumor involvement of the lymph nodes (>2mm).

 5. Patients with bilateral breast cancers are eligible.

 6. Patients with pN2a (metastasis in four to nine axillary lymph nodes) are eligible as
 are patients with pN3a (ten or more axillary lymph nodes). Patients with
 infraclavicular lymph node involvement are NOT eligible.

 7. Patients must have clinically measurable disease to be treated in the neoadjuvant
 setting. This includes patients with a non-palpable primary who have histologically
 proven lymph node (LN) involvement that is clinically palpable and measurable by
 ultrasound

 8. Histologic confirmation of invasive tumor will be done by core needle biopsy for
 patients with intact primary tumors. If patients have undergone adequate core biopsy
 prior to evaluation at MDACC, repeat core biopsy is optional.

 9. Patients must sign an informed consent indicating that they are aware of the
 investigational nature of the study, in keeping with institutional policy.

 10. Patients with a prior history of breast cancer are eligible if the current primary
 breast cancer is of a higher stage than the original breast cancer and the patient has
 not received any of the current study medications including past doxorubicin.

 11. Patients should have adequate bone marrow function, as defined by peripheral
 granulocyte count of > 1,500/mm3, and platelet count > 100,000/mm3. Patients must have
 adequate liver function with a bilirubin within normal laboratory values.
 Transaminases (SGPT) may be up to 2.5x upper limit of normal (ULN) if alkaline
 phosphatase is < ULN or alkaline phosphatase may be up to 4 x ULN if transaminases are
 < ULN.

 12. In addition, patients should have adequate renal function, defined as a serum
 creatinine < 2.5 mg% and/or creatinine clearance greater than 51 ml/min as calculated
 by Cockcroft and Gault Equation: Cockcroft and Gault Equation: Creatinine clearance
 for males = {(140 - age [yrs])(body weight [kg])}/{(72) (serum creatinine [mg/dL])}.
 Creatinine clearance for females = 0.85 x male value

 13. Patients who had surgical therapy prior to referral will be eligible for randomization
 to systemic chemotherapy administered in the adjuvant setting.

 14. Patients who have overexpression of the her-2/neu oncogene are eligible for the study.

 Exclusion Criteria:

 1. Patients with N2 (clinical staging) or N3 (clinical staging) nodal disease,
 inflammatory breast cancer, or metastatic disease are not eligible. This includes
 patients with infraclavicular and/or supraclavicular lymph node involvement. Patients
 with pN2a (metastasis in four to nine axillary lymph nodes) are eligible.

 2. Patients with pN2b (metastasis in clinically apparent internal mammary lymph nodes in
 the absence of axillary lymph node metastasis) are not eligible. Patients with T4
 lesions in the neoadjuvant setting are not eligible. Patients with limited T4 lesions
 in the adjuvant setting (for example, focal extension into the skin with negative
 margins) are eligible.

 3. Severe hypersensitivity reactions to agents formulated in either cremophor or
 polysorbate 80 must be excluded. Patients with hypersensitivity reactions to any of
 the study medications must be excluded.

 4. Those patients with history of other malignancies will be excluded, except
 non-melanoma skin cancer and non-invasive cervical cancer.

 5. Patients with uncompensated congestive heart failure are not eligible. Patients with
 myocardial infarction within the past 12 months are ineligible.

 6. Patients who are pregnant or lactating are not eligible. Women of childbearing
 potential must have a negative pregnancy test prior to initiation of chemotherapy.
 Women of childbearing potential who will not use a reliable and appropriate
 contraceptive method during the study are not eligible.

 7. Patients who have had an organ allograft are ineligible.

 8. Patients with serious concurrent infections are ineligible.

 9. Sexually active male patients unwilling to practice contraception during the study are
 ineligible.

 10. Patients with pre-existing peripheral neuropathy > grade 1.