Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III, Phase II Treatment Closed 18 to 69 WCCC-CO-8111 NCI-D81-048-515

Objectives

I.  Define the relative roles of systemic and local treatments in the care of 
resectable locally advanced primary breast cancer.
II.  Assess the relative effectiveness of intensive chemotherapy versus 
mastectomy as the initial method for debulking Stage III breast cancer.
III.  Evaluate radiation therapy after mastectomy and radiation therapy and 
implants for controlling chemotherapeutically debulked Stage III disease.
IV.  Determine the toxicity of the various components of an intensive 
multimodality treatment plan.

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Patient Characteristics:

See General Eligibility Criteria

General Eligibility Criteria:

Female patients 18 to 69 years of age 
with histologically proven Stage III, resectable, locally advanced, primary 
breast carcinoma.  Eligible TNM clinical stages are:  T3, T4, N0, N1, N2, M0; 
patients with T3 lesions (greater than 5 cm) who are node negative are 
eligible.  Patients must have a performance status of 3 or better and adequate 
hematologic, renal, and hepatic function, i.e., WBC and platelets at least 
4,000 and 100,000, respectively, creatinine no greater than 1.5 mg%, SGOT no 
greater than 60 iu/ml, and bilirubin no higher than 1.5 mg%.  A creatinine 
clearance above 80 is required only in patients to be treated on Regimen B.  
Chest x-ray and bone scan must be normal, or any abnormality must be due to 
nonmalignant causes as documented by skeletal x-rays and/or biopsy.  Patients 
with the breast already removed must have undergone at least a total 
mastectomy and axillary dissection with gross and microscopically free 
margins, leaving the patient clinically free of disease; the interval between 
surgery and study entry may be no more than 10 weeks.  Patients must be 
previously untreated (except for surgery).  There must be no prior or 
concurrent malignancy except for curatively treated basal cell or squamous 
cell skin cancer or carcinoma in situ of the cervix.  Patients who are 
pregnant, those who are poor medical or surgical risks, and those with 
psychiatric disorders are ineligible.  Patients entering this study should 
also be entered on protocol WCCC-CO-8434.

Expected Enrollment

30 patients will be required.

Outline

Nonrandomized study.  Patients with resectable tumors enter Regimen A and then 
Regimen B.  Patients entering this study following Surgery, patients whose 
tumors are not resectable, and patients who refuse mastectomy enter Regimen B 
and then Regimen C.  Patients with initially nonresectable tumors that are 
converted to resectable by Regimen B therapy may elect to be treated on 
Regimen A before proceeding to Regimen C.  Patients who do not undergo 
mastectomy will receive interstitial implant therapy on Regimen C.  Patients 
may be treated on Regimen B if they live within 2.5 hours of the UWCCC or are 
able to reside within that time frame when clinically indicated for patient 
safety, e.g., when total granulocytes are below 1,000/cumm; otherwise, they 
are treated on Regimen B-Alternate.  As of September 1988, Regimen B has been 
closed to patient entry; all patients otherwise to be treated on Regimen B are 
now treated on Regimen B-Alternate.
Regimen A:  Surgery.  Mastectomy and axillary dissection.
Regimen B (Regimen closed September 1988):  Sequential 2-Drug Combination 
Chemotherapy, Single-agent Chemotherapy, Single-agent Hormone Therapy, 2-Drug 
Hormone Therapy plus 2-Drug Combination Chemotherapy, followed by Single-agent 
Hormone Therapy.  Adriamycin, ADR, NSC-123127; Vincristine, VCR, NSC-67574; 
followed by Dibromodulcitol, DBD, NSC-104800; followed by Prednisone, PRED, 
NSC-10023; followed by Tamoxifen, TMX, NSC-180973; Fluoxymesterone, FLU, 
NSC-12165; plus Hexamethylmelamine, HMM, NSC-13875; Methotrexate, MTX, NSC-740 
with Citrovorum Factor, CF, NSC-3590; followed by PRED.
Regimen B-Alternate:  3-Drug Combination Chemotherapy plus 2-Drug Hormonal 
Therapy.  CAFTH:  Cyclophosphamide, CTX, NSC-26271 (or Melphalan, L-PAM, 
NSC-8806, if indicated); ADR; 5-Fluorouracil, 5-FU, NSC-19893; TMX; FLU.
Regimen C:  Radiotherapy.  Breast or chest wall irradiation by external beam 
(Co-60) or interstitial implant.  Co-60 or higher energy photons may be 
combined with electron beam therapy, or photons may be entirely substituted 
for electrons for some treatment portals, especially for the internal mammary 
lymph node region near the sternum.

Trial Contact Information

Trial Lead Organizations

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

William H. Wolberg, MD, Protocol chair(Contact information may not be current)		Ph: 608-263-2521; 800-622-8922