Phase III Adjuvant Chemotherapy with Intensive CEF (CTX/EPI/5-FU) vs Standard CMF (CTX/MTX/5-FU) in Premenopausal Patients with Carcinoma of the Breast with Positive Axillary Nodes
Last Modified: 1/16/2007
Basic Trial Information Objectives Entry Criteria Expected Enrollment Outline Published Results Related Publications Trial Contact Information
Basic Trial Information
Phase | Type | Status | Age | Protocol IDs |
---|
Phase III | Treatment | Closed | pre/perimenopausal | CAN-NCIC-MA5 NCI-V90-0027, MA5 |
Objectives
I. Compare, in a Phase III setting, the relapse-free survival and overall
survival of premenopausal women with node-positive breast cancer who have
undergone complete surgical resection of all known disease and are
subsequently randomized to adjuvant chemotherapy consisting of intensive CEF
(cyclophosphamide/epirubicin/fluorouracil) vs. standard CMF
(cyclophosphamide/methotrexate/fluorouracil).
II. Compare the toxicities of these two regimens when administered as
adjuvant therapy in this patient population.
III. Compare the quality of life among patients receiving these adjuvant
chemotherapy regimens.
Entry Criteria Disease Characteristics:
Breast adenocarcinoma with at least one histologically positive
axillary node that has been completely resected
Total or partial mastectomy with axillary node dissection
required
If less than total mastectomy, breast irradiation on protocol
following completion of adjuvant chemotherapy required
Complete resection of bilateral breast cancer required but
contralateral axillary dissection optional if axilla
clinically negative at surgery
No evidence of microscopic residual disease in axilla
following either procedure or in resection margins following
total mastectomy
Further excision recommended for residual microscopic margins
following partial mastectomy
If further excision not undertaken, boost irradiation to
tumor bed in addition to breast irradiation required
following chemotherapy on protocol
Preoperative clinical Stage T1-3a, N0-2, M0 required
Clinical Stage T4 excludes (chest wall extension; edema,
including peau d'orange; skin ulceration; satellite skin
nodules confined to homolateral breast; and inflammatory
carcinoma)
Postoperative pathologic Stage T0-4, N1-2, M0 (only T4 with
dermal involvement on pathologic exam allowed)
No evidence of metastatic disease on appropriate studies (e.g.,
chest x-ray, bone scan/x-ray, abdominal ultrasound if LFTs
abnormal)
Randomization within 10 weeks of initial surgical histologic
diagnosis required
Hormone receptor status:
Not specified
Prior/Concurrent Therapy:
No prior therapy for breast cancer
Biologic therapy:
Not specified
Chemotherapy:
No planned other cytotoxic chemotherapy
Endocrine therapy:
No planned tamoxifen, long-term prednisone, or other hormones
Radiotherapy:
No planned regional nodal or chest wall irradiation
Surgery:
Prior partial or total mastectomy required (see Disease
Characteristics)
Patient Characteristics:
Age:
Not specified
Sex:
Females only
Menopausal status:
Pre- or perimenopausal, i.e., one of the following:
Normal menstruation
Biochemical evidence of ovarian function
Amenorrheic for less than 1 year
Amenorrheic for 1-3 years and under age 52
Hysterectomized but with at least 1 ovary intact and under
age 56
Performance status:
Not specified
Hematopoietic:
WBC at least 3,000
ANC at least 1,500
Platelets at least 100,000
Hepatic:
Bilirubin within normal limits
Alkaline phosphatase within normal limits
SGOT/SGPT within normal limits
If LFTs are elevated, metastasis must be ruled out by
abdominal ultrasound
Renal:
Creatinine no greater than 1.5 x normal
Cardiovascular:
LVEF at least 45% by MUGA
No history of angina
No current CHF
No documented MI
Other:
No serious underlying medical illness or psychiatric or
addictive disorder that might interfere with adequate drug
delivery and follow-up
No history of second malignancy except:
Treated nonmelanomatous skin cancer
Curatively treated cancer of the cervix, endometrium,
colon, or thyroid with no evidence of active disease
for at least 5 years
Expected Enrollment
600 patients will be enrolled over about 4 years. Outline
Randomized study. Patients who have undergone less than total mastectomy
receive radiotherapy on Regimen A upon completion of adjuvant chemotherapy.
Arm I: 3-Drug Combination Chemotherapy. CEF: Cyclophosphamide, CTX,
NSC-26271; Epirubicin, EPI, NSC-256942; Fluorouracil, 5-FU, NSC-19893.
Arm II: 3-Drug Combination Chemotherapy. CMF: CTX; Methotrexate, MTX,
NSC-749; 5-FU.
Regimen A: Radiotherapy. Breast irradiation using Co60 equipment or a linear
accelerator with energies of 4 MeV or greater and (in selected cases) boost
irradiation of the tumor bed with Co60 or electrons.
Published ResultsO'Malley FP, Chia S, Tu D, et al.: Topoisomerase II alpha protein overexpression has predictive utility in a randomized trial comparing CMF to CEF in premenopausal women with node positive breast cancer (NCIC CTG MA.5). [Abstract] Breast Cancer Res Treat 100 (Suppl 1): A-38, S18, 2006. Pritchard KI, Shepherd LE, O'Malley FP, et al.: HER2 and responsiveness of breast cancer to adjuvant chemotherapy. N Engl J Med 354 (20): 2103-11, 2006.[PUBMED Abstract] Shepherd LE, Parulekar W, Pritchard KI, et al.: Left ventricular function following adjuvant chemotherapy for breast cancer: the NCIC CTG MA5 experience. [Abstract] J Clin Oncol 24 (Suppl 18): A-522, 2006. Levine MN, Pritchard KI, Bramwell VH, et al.: Randomized trial comparing cyclophosphamide, epirubicin, and fluorouracil with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer: update of National Cancer Institute of Canada Clinical Trials Group Trial MA5. J Clin Oncol 23 (22): 5166-70, 2005.[PUBMED Abstract] Parulekar WR, Day AG, Ottaway JA, et al.: Incidence and prognostic impact of amenorrhea during adjuvant therapy in high-risk premenopausal breast cancer: analysis of a National Cancer Institute of Canada Clinical Trials Group Study--NCIC CTG MA.5. J Clin Oncol 23 (25): 6002-8, 2005.[PUBMED Abstract] Radice D, Redaelli A: Q-TWiST analysis of cyclophosphamide, epirubicin, fluorouracil versus cyclophosphamide, methotrexate, fluorouracil treatment for premenopausal women with node-positive breast cancer. Pharmacoeconomics 23 (1): 69-75, 2005.[PUBMED Abstract] Pritchard KI, O'Malley FA, Andrulis I, et al.: Prognostic and predictive value of HER2/neu in a randomized trial comparing CMF to CEF in premenopausal women with axillary lymph node positive breast cancer (NCIC CTG MA.5). [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-165, 2002. Levine MN, Bramwell VH, Pritchard KI, et al.: Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 16 (8): 2651-8, 1998.[PUBMED Abstract] Levine M, Bramwell V, Bowman D, et al.: A clinical trial of intensive CEF versus CMF in premenopausal women with node positive breast cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 14: A-112, 103, 1995. Related PublicationsGennari A, Sormani MP, Puntoni M, et al.: A pooled analysis on the interaction between HER-2 expression and responsiveness of breast cancer to adjuvant chemotherapy. [Abstract] Breast Cancer Res Treat 100 (Suppl 1): A-41, S19, 2006. Findlay B, Myles J, Levine M, et al.: Using ideal vs. actual weights to calculate chemotherapy doses in premenopausal women with stage 2 breast cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 13: A-56, 63, 1994.
Trial Contact Information
Trial Lead Organizations NCIC-Clinical Trials Group ![](https://webarchive.library.unt.edu/eot2008/20090510112426im_/http://www.cancer.gov/images/spacer.gif) | ![](https://webarchive.library.unt.edu/eot2008/20090510112426im_/http://www.cancer.gov/images/spacer.gif) | ![](https://webarchive.library.unt.edu/eot2008/20090510112426im_/http://www.cancer.gov/images/spacer.gif) | Mark Levine, MD, Protocol chair(Contact information may not be current) | ![](https://webarchive.library.unt.edu/eot2008/20090510112426im_/http://www.cancer.gov/images/spacer.gif) | Ph: 905-527-4322 ext. 42176 |
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Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. |