Phase III Randomized Study of Adjuvant CA (Cyclophosphamide/Doxorubicin) Comparing Standard- vs Intermediate- vs High-Dose Doxorubicin, with vs without Subsequent Paclitaxel, in Women with Node-Positive Breast Cancer
Adjuvant Combination Chemotherapy in Node-Positive Breast Cancer
Basic Trial Information
|Phase III||Treatment||Closed||over 18||NCI||CLB-9344|
E-C9344, NCCTG-943051, SWOG-9410, INT-0148
I. Determine whether higher doses of doxorubicin (DOX) used in an adjuvant regimen with cyclophosphamide (CTX) increase disease-free and overall survival in patients with early stage breast cancer. II. Determine whether paclitaxel (TAX) following 4 courses of CTX/DOX (CA) further improves disease-free and overall survival compared to CA alone. III. Determine whether TAX improves disease-free and overall survival at 3 different doses of DOX in the CA regimen, especially whether TAX following standard-dose DOX/CTX is more effective than high-dose DOX/CTX without TAX. IV. Assess the incidence of life-threatening and lethal toxicity with different doses of DOX in the CA regimen, with and without subsequent TAX. V. Determine whether the longer duration of chemotherapy for patients receiving TAX is associated with a reduction in local recurrence in patients whose definitive treatment was lumpectomy plus radiotherapy. VI. Assess the differences among the treatments in actual chemotherapy delivered, percentage of patients who experience delays in treatment delivery because of neutropenia and other treatment-related toxicity, number of hospital days required for recovery from febrile neutropenia on each course, and the incidence of platelet and erythrocyte transfusions on each course.
Histologically confirmed adenocarcinoma of the breast with one or more positive lymph nodes (T1-3, N1, M0) that is considered operable (clinical stage N1 eligible) No locally advanced disease in the judgment of the investigator, e.g.: No fixed tumors No peau d'orange skin change No skin ulcerations No inflammatory disease Patients with 10 or more histologically involved axillary nodes eligible only if treatment on protocol CLB-9082 or EST-2190 (bone marrow transplantation) is refused Definitive resection required: Modified radical mastectomy or segmental mastectomy with axillary node dissection within 84 days prior to entry No evidence of gross or microscopic disease in the resection margins Standard radiotherapy for segmental mastectomy patients administered after completion of all chemotherapy Hormone receptor status: Any ER or PgR status
Biologic therapy: Not specified Chemotherapy: No prior chemotherapy for current malignancy No prior chemotherapy that has compromised bone marrow reserves or other organ function Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy for current malignancy No prior radiotherapy that has compromised bone marrow reserves or other organ function Surgery: Definitive resection required (see Disease Characteristics)
Age: Over 18 Sex: Women only Menopausal status: Pre- and postmenopausal Performance status: Zubrod 0-1 Life expectancy: At least 2 years Hematopoietic: WBC at least 3,000/mm3 Platelet count at least 100,000/mm3 Hemoglobin at least 9 g/dL Hepatic: Bilirubin less than 1.5 times normal Renal: Creatinine less than 1.5 times normal Cardiovascular: Left ventricular ejection fraction normal No myocardial infarction within 6 months No congestive heart failure No other uncontrolled or severe cardiovascular disease Arrhythmia requiring treatment allowed at the discretion of the physician Other: No active bacterial, viral, or fungal infection No clinically defined AIDS No serious medical illness that would limit survival to less than 2 years No psychiatric condition that would prevent informed consent No concurrent metastatic disease from a second cancer that would interfere with interpretation of results No morbid obesity that would preclude full-dose treatment Not pregnant or lactating Effective contraception required during and for at least 2 months following therapy Blood/body fluid analyses to determine eligibility and physical exams completed within 14 days prior to registration EKG, x-rays, and bone scans obtained within 80 days prior to registration
About 3,000 patients will be entered over 3 years. If accrual is insufficient after either 1 or 2 years, Arm II will be closed.
This is a randomized study. Patients are stratified by participating institution. Patients are randomized to one of three doses of doxorubicin and then randomized within each group to receive paclitaxel or not. The first group receives cyclophosphamide and standard-dose doxorubicin. The second group receives cyclophosphamide and medium-dose doxorubicin. The third group receives cyclophosphamide and high-dose doxorubicin. All groups receive 4 courses of therapy at 3-week intervals. Within each group, one half of the patients receive paclitaxel every 3 weeks for 4 weeks. All receptor-positive patients receive oral tamoxifen daily for 5 years. No other chemotherapy or hormonal therapy is permitted except steroids as antiemetics or for adrenal failure. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and yearly thereafter.
Lara JF, Thor AD, Dressler LG, et al.: p53 Expression in node-positive breast cancer patients: results from the Cancer and Leukemia Group B 9344 Trial (159905). Clin Cancer Res 17 (15): 5170-8, 2011.[PUBMED Abstract]
Berry DA, Thor AD, Jewell SD, et al.: Benefits of adding paclitaxel to adjuvant doxorubicin/cyclophosphamide depending on HER2 & ER status: analysis of tumor tissue microarrays and immunohistochemistry in CALGB 9344 (Intergroup 0148). [Abstract] 32nd Annual San Antonio Breast Cancer Symposium, December 9-13, 2009, San Antonio, Texas. A-606, 2009.
Hayes DF, Thor AD, Dressler LG, et al.: HER2 and response to paclitaxel in node-positive breast cancer. N Engl J Med 357 (15): 1496-506, 2007.[PUBMED Abstract]
Sartor CI, Peterson BL, Woolf S, et al.: Effect of addition of adjuvant paclitaxel on radiotherapy delivery and locoregional control of node-positive breast cancer: cancer and leukemia group B 9344. J Clin Oncol 23 (1): 30-40, 2005.[PUBMED Abstract]
Henderson IC, Berry DA, Demetri GD, et al.: Improved outcomes from adding sequential Paclitaxel but not from escalating Doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol 21 (6): 976-83, 2003.[PUBMED Abstract]
Sartor CI, Fitzgerald TJ, Laurie F, et al.: Effect of addition of adjuvant paclitaxel on radiotherapy delivery and locoregional control for node positive breast cancer in CALGB 9344. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-38, 10, 2003.
Henderson IC, Berry D, Demetri G, et al.: Improved disease-free (DFS) and overall survival (OS) from the additon of sequential paclitaxel (T) but not from the escalation of doxorubicin (A) dose level in the adjuvant chemotherapy of patients (PTS) with node-positive primary breast cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 17: A390A, 101a, 1998.
Lamont EB, Herndon JE 2nd, Weeks JC, et al.: Measuring clinically significant chemotherapy-related toxicities using Medicare claims from Cancer and Leukemia Group B (CALGB) trial participants. Med Care 46 (3): 303-8, 2008.[PUBMED Abstract]
Muss HB, Berry DA, Cirrincione C, et al.: Toxicity of older and younger patients treated with adjuvant chemotherapy for node-positive breast cancer: the Cancer and Leukemia Group B Experience. J Clin Oncol 25 (24): 3699-704, 2007.[PUBMED Abstract]
Berry DA, Cirrincione C, Henderson IC, et al.: Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA 295 (14): 1658-67, 2006.[PUBMED Abstract]
Giordano SH, Duan Z, Kuo YF, et al.: Impact of a scientific presentation on community treatment patterns for primary breast cancer. J Natl Cancer Inst 98 (6): 382-8, 2006.[PUBMED Abstract]
Lamont EB, Herndon JE 2nd, Weeks JC, et al.: Measuring disease-free survival and cancer relapse using Medicare claims from CALGB breast cancer trial participants (companion to 9344). J Natl Cancer Inst 98 (18): 1335-8, 2006.[PUBMED Abstract]
Muss H, Berry D, Cirrincione C, et al.: Toxicity of older and younger patients (pts) treated (Rx) with intensive adjuvant chemotherapy (Cx) for node-positive (N+) breast cancer (BC): the CALGB experience. [Abstract] J Clin Oncol 24 (Suppl 18): A-559, 2006.
Campone M, Fumoleau P, Bourbouloux E, et al.: Taxanes in adjuvant breast cancer setting: which standard in Europe? Crit Rev Oncol Hematol 55 (3): 167-75, 2005.[PUBMED Abstract]
Lamont EB, Herndon JE 2nd, Weeks JC, et al.: Criterion validity of Medicare chemotherapy claims in Cancer and Leukemia Group B breast and lung cancer trial participants. J Natl Cancer Inst 97 (14): 1080-3, 2005.[PUBMED Abstract]
Muss HB, Woolf S, Berry D, et al.: Adjuvant chemotherapy in older and younger women with lymph node-positive breast cancer. JAMA 293 (9): 1073-81, 2005.[PUBMED Abstract]
Berry DA, Cirrincione C, Henderson IC, et al.: Effects of improvements in chemotherapy on disease-free and overall survival of estrogen-receptor negative, node-positive breast cancer: 20-year experience of the CALGB U.S. Breast Intergroup. [Abstract] Breast Cancer Res Treat 88 (Suppl 1): A-29, 2004.
Dougherty MK, Schumaker LM, Jordan VC, et al.: Estrogen receptor expression and sensitivity to paclitaxel in breast cancer. Cancer Biol Ther 3 (5): 460-7, 2004.[PUBMED Abstract]
Piccart MJ, Lohrisch C, Duchateau L, et al.: Taxanes in the adjuvant treatment of breast cancer: why not yet? J Natl Cancer Inst Monogr (30): 88-95, 2001.[PUBMED Abstract]
Annemans L, Moeremans K, Henderson I, et al.: Cost-effectiveness of the sequential addition of taxol (T) to doxorubicin plus cyclophosphamide (AC) in the adjuvant chemotherapy of patients with node-positive breast cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 19: A-1752, 2000.
Trial Contact Information
Trial Lead Organizations
Cancer and Leukemia Group B
Ph: 415-353-7070; 800-888-8664
Eastern Cooperative Oncology Group
Ph: 215-728-2689; 888-369-2427
Southwest Oncology Group
North Central Cancer Treatment Group
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.