4. Neoadjuvant Systemic Therapy

4.1 Phase III Randomized Study of Preoperative Doxorubicin and Cyclophosphamide (AC) Versus Preoperative AC Followed by Docetaxel Versus Preoperative AC and Postoperative Docetaxel in Women with Operable Carcinoma of the Breast

Objectives

I. Compare overall and disease-free survival in patients with operable adenocarcinoma of the breast treated with 4 courses of preoperative doxorubicin and cyclophosphamide (AC) alone vs 4 courses of preoperative or postoperative docetaxel (TXT) following 4 courses of preoperative AC.

II. Evaluate whether the addition of preoperative TXT to preoperative AC results in improved rates of clinical and pathologic locoregional tumor response.

III. Assess whether the addition of preoperative TXT to preoperative AC results in improved rates of breast conservation.

IV. Assess whether postoperative TXT improves disease-free and overall survival in patients who receive preoperative AC, especially in certain subgroups of patients (e.g., those with pathologically positive nodes).

Participation Criteria

• Invasive adenocarcinoma of the breast.
  
  
• Tumor palpable on clinical exam and confined to the breast and ipsilateral axilla.
  
  
• If clinically negative axillary nodes (N0): primary tumor greater than 1 cm (T1c-T3).
  
  
• If clinically positive axillary nodes (N1): any size primary tumor (T1-3).
  
  
• No ulceration, erythema, skin infiltration (complete fixation), peau d'orange, or skin edema of any magnitude. Tethering or dimpling of skin or nipple inversion allowed.
  
  
• None of the following unless proven benign on biopsy:
  
  
  • Suspicious palpable nodes in contralateral axilla
    
    
  • Palpable supraclavicular or infraclavicular nodes

• Any ER/PR status

AC = Doxorubicin and Cyclophosphamide

Harry D. Bear, Chair
Ph: 804-828-9325 National Surgical Adjuvant Breast and Bowel Project

4.2 Phase III Randomized Neoadjuvant Study of ICI 182780 in Women with Stage I or II Primary Breast Cancer

Objectives

I. Determine the inhibitory effect of ICI 182780 on the development of metastasis, as measured by disease-free survival and overall survival, in women with operable stage I or II primary breast cancer.

II. Determine toxicity of this regimen in these patients.

Participation Criteria

• Histologically or cytologically confirmed stage I or II primary operable breast cancer
  
  
• Surgery planned within next 1-4 weeks?
  
  
• Hormone receptor status:
  
  
  • Estrogen receptor positive or unknown
    
    
  • No known estrogen receptor negative tumor
    
    
  • Unknown progesterone receptor status eligible

• Menopausal status: Premenopausal or postmenopausal

Protocol

This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to participating center and menopausal status (premenopausal vs postmenopausal). Patients are randomized to receive either ICI 182780 IM or placebo IM over 2 minutes on day 1. Patients undergo surgery between days 8 and 29.

Cornelis J.H. van de Velde, Principal Investigator
Ph: 31-71-5262309 Leiden University Medical Center Leiden, Netherlands EORTC Breast Cancer Group

Anthony Howell, Principal Investigator
Ph: 446-3746 ext 0161 Christie Hospital N.H.S. Trust Manchester, England, United Kingdom Breast International Group

4.3 Phase II Pilot Study of cDNA Microarray as a Measure of Tumor Response to Neoadjuvant Docetaxel and Capecitabine Followed by Surgery and Adjuvant Doxorubicin and Cyclophosphamide in Patients With Stage II or III Breast Cancer

Objectives

I. Evaluate the feasibility of using cDNA microarray as a measure of a tumor's biological response to neoadjuvant docetaxel and capecitabine followed by surgery and adjuvant doxorubicin and cyclophosphamide by characterizing the cDNA expression patterns before and after chemotherapy in patients with stage II or III breast cancer.

II. Determine the toxicities of this regimen in these patients.

III. Determine the clinical and pathologic response rate of patients treated with this regimen.

Participation Criteria

• Hormone receptor status: Receptor status known.
  
  
• Histologically confirmed stage II or III breast cancer.
  
  
• Tumor size greater than 2 cm.
  
  
• Prior biopsy allowed if adequate tumor tissue remains for second biopsy.

Protocol

Patients receive docetaxel IV over 1 hour on day 1 and oral capecitabine twice daily on days 2-15 every 21 days for 4 courses. Following surgery, patients receive doxorubicin IV and cyclophosphamide IV over 30 minutes on day 1 every 21 days for 4 courses. Patients who undergo lumpectomy and axillary lymph node dissection receive standard radiotherapy following the completion of chemotherapy. Patients who undergo a modified radical mastectomy may receive chest wall radiation. Patients with estrogen or progesterone receptor-positive disease receive oral tamoxifen daily for 5 years.

Tumor tissue is collected at baseline, day 2 of course 1 of neoadjuvant chemotherapy, prior to course 2 of neoadjuvant chemotherapy, and at surgery. These samples are subjected to reverse transcriptase polymerase chain reaction and cDNA microarray analysis, in order to evaluate gene expression ratios before and after chemotherapy.

JoAnne Zujewski, Chair
Division of Clinical Sciences Principal Investigator, Ph: 301-402-0985 Medicine Branch Bethesda, Maryland

4.4 Phase III Randomized Study of Neoadjuvant Fluorouracil/Doxorubicin/ Cyclophosphamide (FAC) vs Cyclophosphamide/Methotrexate/Fluorouracil (CMF) for Stage III Breast Cancer, with Quality of Life Assessed in Patients Converted to Conservative Surgery vs Those Who Are Not

Objectives

I. Compare the response to neoadjuvant therapy with fluorouracil, doxorubicin, and cyclophosphamide (FAC) vs. cyclophosphamide, methotrexate, and fluorouracil (CMF) in patients with stage III breast cancer.

II. Compare the rate of breast conservation and local-regional control with these two regimens.

III. Assess the disease-free and overall survival associated with each regimen.

IV. Assess the toxic effects, cosmetic results after conservative surgery, quality of life, and patient compliance associated with each treatment.

Participation Criteria

• Breast cancer histologically confirmed by tru-cut needle biopsy vs Measurable, stage III (UICC staging system) disease.
  
  
• No inflammatory breast cancer.

Randomization

Bernardo A. Leone, Chair
Ph: 54-299-4485247 Grupo Oncologico Cooperativo del Sur

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