Full Protocol (members only)   Consent Form   HIPAA   Spanish Consent Form

NSABP B-36 - "A Clinical Trial of Adjuvant Therapy Comparing Six Cycles of 5-Fluorouracil, Epirubicin, and Cyclophosphamide (FEC) to Four Cycles of Adriamycin and Cyclophosphamide (AC) in Patients With Node-Negative Breast Cancer"

Treatment Plan    (Supplied Drug:  Epirubicin)

RANDOMIZATION

Group 1* - (q 21 days, x 4 cycles)

Adriamycin:  60mg/m², IV over 15 mins

Cyclophosphamide:  600mg/m², IV over 30 mins

Group 2* - (q 21 days, x 6 cycles)

5-FU:  500mg/m², IV push

Epirubicin:  100mg/m², IV over 15 mins

Cyclophosphamide:  500mg/m², IV over 30 mins

*   1)  Pts w/ER+ &/or PgR+ tumors will receive hormonal therapy beginning >3 wks and <12 wks following last dose of chemo x minimum of 5 yrs.  See protocol for hormonal therapy requirements.

    2)  All women treated w/lumpectomy will receive whole breast RT, beginning as soon as possible after last chemo dose.  Regional nodal RT is prohibited.

Eligibility

• Age >18.

• Life expectancy >10 yrs, excluding breast cancer dx.

• <84 days between last surgery for breast cancer (lumpectomy, mastectomy, sentinel lymph node bx, axillary surgery, or re-excision of lumpectomy margins) and randomization.

• Tumor must be invasive adenocarcinoma on histol exam.  No pure tubular or mucinous adenocarcinomas.

• Prim tumor must be T1-3 by clin and path evaluation.

• Lymph nodes from all axillary staging must be pN0 (AJCC Cancer Staging Manual, 6th ed.).

• Must have ER analysis performed on prim tumor pre-randomiz.  If ER-, then PgR analysis must be performed.  If ER+, PgR analysis is desired, but not mandatory.  "Marginal" or "borderline" results will be considered positive regardless of methodology used.

• Must have had either lumpectomy or total mastectomy.

• Must have undergone axillary nodal staging procedures (SN bx alone, SN bx followed by axillary sampling or complete dissection, or axillary node dissection to obtain lymph nodes for path eval).  If pt has palpable nodes, axillary dissection is required.

• No clinical or radiologic evidence of mets disease.

• Pts w/skeletal pain are eligible if bone scan or roentgenological exam fail to disclose mets disease.  Suspicious findings must be confirmed benign by xray, MRI, or bx.

• Menopausal status must be determined pre-randomiz.  Pre- & post-menopausal women are eligible.  "Post-menopausal" defined as:

  • prior documented bilat oophorectomy, or

  • >12 mos w/o spontaneous menstrual bleeding, or

  • age >55 w/prior hysterectomy, or

  • age <54 w/prior hysterectomy, w/o oophorectomy (or status of ovaries unknown), w/documented FSH level demonstrating confirmatory elevation in lab's postmenopausal range.

• Within 3 mos pre-entry:   Baseline LVEF by MUGA or echo >LLN for facility.

• At randomiz (all post-op):   AGC >1500/mm3 (or >1200/mm3 if representing ethnic/racial variation - investigator's opinion); platelets >100,000/mm3 (exclude significant underlying hematologic disorders); total bili <ULN (unless chronic Grade 1 elevation [>ULN to 1.5x ULN] due to Gilbert's disease or similar syndrome due to slow conjugation); alk phos <2.5x ULN; SGOT <1.5x ULN; serum creat <ULN.

• Pts w/hx of non-breast malignancies are eligible if disease-free >5 yrs pre-randomiz and at low risk for recurrence (physician's opinion).  Following dxs are eligible if diagnosed and treated w/i past 5 yrs:  carcinoma in situ of cervix, melanomain situ,  and non-melanoma skin cancer.

• No male pts.

• No bilat malignancy (including DCIS) or mass or mammographic abnormality in opposite breast suspicious for malignancy unless bx-proven to be not malignant.

• No suspicious palpable nodes in ipsilateral or contralateral axilla or palpable supraclavicular or infraclavicular nodes (unless bx-proven not involved w/tumor).

• No prior hx of breast cancer, including DCIS (hx of LCIS is allowed).

• No tx including RT, chemo, biotherapy, &/or hormonal therapy administered for currently diagnosed breast cancer pre-randomiz.  Only exceptions:  1) hormonal therapy, which may be given up to total of 28 days anytime after dx & b/f study entry.  Hormonal therapy must stop at or b/f randomiz and re-start (if indicated), following chemo; 2) if pt is enrolled on NSABP B-39 and randomized to Group 2, PBI may be completed prior to starting tx on NSABP B-36.

• No prior anthracycline for any malignancy.

• No sex hormonal therapy (unless discontinued pre-randomiz).

• No therapy w/hormonal agents such as Raloxifene, Tamoxifen, or other SERMs, either for osteoporosis or breast cancer prevention, unless discontinued pre-randomiz.  Except for Tamoxifen, these are not permitted while on study.

• No cardiac disease to preclude use of anthracyclines.

• No non-malignant systemic disease to preclude any tx option or prolonged follow-up.

• No pregnancy or lactation at randomiz.  Women of reproductive potential must use effective, non-hormonal contraception.

• No concurrent tx w/investigational agents.

• No psychiatric, addictive disorders, or other conditions precluding pt from meeting study requirements (investigator's opinion).

• PRESTUDY REQUIREMENTS:

  • H&P*

  • Pelvic exam (women w/uterus who will receive Tamoxifen) - (within 1 yr pre-randomiz)

  • CBC/diff/platelets**

  • Serum creat**

  • Bili**

  • SGOT**

  • Alk phos**

  • CXR (PA & Lat) or Chest CT*

  • Bone imaging (only if symptoms present; bone scan &/or roentgenological exam)

  • Bilat mammogram (w/i 6 mos pre-randomiz; unilateral for pts w/mastectomy)

  • EKG*

  • MUGA or Echo*

  • QOL asmt

  • Menstrual hx

  • Menopausal status

  • FSH (if needed to determine menopausal status)

  • Serum collection (after randomiz, but b/f chemo begins - contact KCCOP for kit))#

  • Tumor block collection (submit index tumor blocks w/i 3 mos from randomiz)

  *     Within 3 mos pre-randomiz

  **    Post-op testing

  #     Three 10-ml red-top vacutainer tubes (no silica or polymer) & one 10-ml yellow-top ACD vacutainer tubes of blood.  Refrigerate yellow-top tube.  Process red-top tubes per protocol.  Ship same day as collected using a refrigerant pack.  Ship Mon-Thurs via NSABP's pre-arranged priority overnight carrier to:  Baylor College of Medicine Breast Center; NSABP Serum Bank; Houston, TX.

• Signed & dated informed consent.

ADDITIONAL ELIGIBILITY REQUIREMENTS FOR LUMPECTOMY PTS (lumpectomy followed by required breast RT)

• Pts treated w/lumpectomy for tumors >5cm are eligible if criteria for lumpectomy are met.

• Margins of resected specimen must be histol-free of invasive tumor and DCIS.  If path exam demonstrates tumor present at line of resection, additional oper procedures may be performed to obtain clear margins.  Permissible even if axillary dissection has been performed.  If tumor still present at resected margin after re-excision(s), pt must undergo total mastectomy to be eligible.

• This is a node negative study; RT of regional lymph nodes is prohibited in this study.

• Whole breast RT is required unless pt is assigned to the partial breast RT group on NSABP B-39.

• No diffuse tumors (demonstrated on mammogram) not surgically amenable to lumpectomy.  (Pt eligible if she undergoes mastectomy).

• No other clinically dominant mass or mammographically suspicious abnormality w/i ipsilateral breast remnant.  Mass must be biopsied and shown histol-benign pre-randomiz, or if malignant, must be surgically removed w/clear margins.

ADDITIONAL ELIGIBILITY REQUIREMENTS FOR MASTECTOMY PTS

• Postmastectomy chest wall RT at investigator's discretion is permitted.  RT of regional lymph nodes is prohibited in this study.