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Phase III Randomized Study of Sequential Chemotherapy Using Doxorubicin, Paclitaxel, and Cyclophosphamide or Concurrent Doxorubicin and Cyclophosphamide Followed By Paclitaxel at 14 and 21 Day Intervals in Women With Node Positive Stage II or IIIA Breast Cancer
Alternate Title Combination Chemotherapy in Treating Patients With Breast Cancer
Objectives I. Compare the sequential chemotherapy with doxorubicin, paclitaxel and cyclophosphamide to combined doxorubicin and cyclophosphamide followed by paclitaxel for disease free and overall survival in women with node positive stage II or IIIA breast cancer. II. Determine whether increasing the dose density of adjuvant chemotherapy will improve disease free and overall survival. III. Compare the toxicity in patients treated with these regimens. Entry Criteria Disease Characteristics: Histologically diagnosed operable, stage II or IIIA adenocarcinoma of the breast One or more positive lymph nodes (T0-3, N1-2, and M0) Metaplastic carcinoma allowed Bilateral breast cancer allowed No metastatic disease Not locally advanced and no tumors fixed to the chest wall, peau d'orange skin changes, skin ulcerations, or clinical inflammatory changes Hormone receptor status: Not specified Prior/Concurrent Therapy: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: No greater than 4 weeks of prior tamoxifen therapy for malignancy No concurrent tamoxifen therapy Radiotherapy: No prior radiation therapy for this malignancy Surgery: No greater than 84 days since prior mastectomy or axillary dissection Patient Characteristics: Age: 18 and over Sex: Female Menopausal status: Not specified Performance status: Not specified Life expectancy: Not specified Hematopoietic: Granulocyte count at least 1000/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin within upper limits of normal Renal: Not specified Cardiovascular: No uncontrolled or severe cardiovascular disease No myocardial infarction within 6 months No congestive heart failure Other: No other serious medical illness No psychoses No active uncontrolled bacterial, viral, or fungal infection HIV negative Not pregnant Expected Enrollment 2000A total of 2,000 patients will be accrued for this study within 22 months. Outline This is a randomized study. Patients are randomized into one of four arms (sequential chemotherapy every 2 weeks vs every 3 weeks vs concurrent chemotherapy followed by paclitaxel every 2 weeks vs every 3 weeks). All tumor should be removed by either a modified radical mastectomy or a segmental mastectomy plus axillary node dissection. Adjuvant chemotherapy is started within 84 days following the last surgical procedure. Arm I: Patients receive sequential chemotherapy every 3 weeks. Doxorubicin IV is administered once every 3 weeks for 4 doses. Paclitaxel IV is then administered over 3 hours once every 3 weeks for 4 doses. Cyclophosphamide IV is administered once every 3 weeks for 4 doses following paclitaxel. Arm II: Patients receive sequential chemotherapy every 2 weeks. Doxorubicin IV is administered once every 2 weeks for 4 doses. Paclitaxel IV is then administered over 3 hours once every 2 weeks for 4 doses. Cyclophosphamide IV is administered once every 2 weeks for 4 doses following paclitaxel. Filgrastim (G-CSF) is administered by subcutaneous injection on days 3-10 after each dose of doxorubicin, paclitaxel, and cyclophosphamide. Arm III: Patients receive combination chemotherapy every 3 weeks. Combination doxorubicin IV and cyclophosphamide IV is administered once every 3 weeks for 4 doses. Paclitaxel IV is administered over 3 hours once every 3 weeks for 4 doses following combination chemotherapy. Arm IV: Patients receive combination chemotherapy every 2 weeks. Combination doxorubicin IV and cyclophosphamide IV is administered once every 2 weeks for 4 doses. Paclitaxel IV is administered over 3 hours once every 2 weeks for 4 doses following combination chemotherapy. G-CSF is administered by subcutaneous injection on days 3-10 after each dose of doxorubicin/cyclophophamide and after each dose of paclitaxel. After completion of all chemotherapy, patients receive tamoxifen orally for 5 years. Patients undergo radiotherapy 4-6 weeks after the completion of chemotherapy. Patients are followed every 6 months for 5 years, then annually until death.Published Results Citron ML, Berry DA, Cirrincione C, et al.: Dose-dense (DD) AC followed by paclitaxel is associated with moderate, frequent anemia compared to sequential (S) and/or less DD treatment: update by CALGB on Breast Cancer Intergroup Trial C9741 with ECOG, SWOG, & NCCTG. [Abstract] J Clin Oncol 23 (Suppl 16): A-620, 33s, 2005. Fornier M, Norton L: Dose-dense adjuvant chemotherapy for primary breast cancer. Breast Cancer Res 7 (2): 64-9, 2005.[PUBMED Abstract] Hudis C, Citron M, Berry D, et al.: Five year follow-up of INT C9741: dose-dense (DD) chemotherapy (CRx) is safe and effective. [Abstract] Breast Cancer Research and Treatment 94 (Suppl 1): A-41, 2005. Schwartz J, Domchek SM, Hwang WT, et al.: Evaluation of anemia, neutropenia and skin toxicities in standard or dose-dense doxorubicin/cyclophosphamide (AC)-paclitaxel or docetaxel adjuvant chemotherapy in breast cancer. Ann Oncol 16 (2): 247-52, 2005.[PUBMED Abstract] Citron ML, Berry DA, Cirrincione C, et al.: Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol 21 (8): 1431-9, 2003.[PUBMED Abstract] Citron M, Berry D, Cirrincione C, et al.: Superiority of dose-dense (DD) over conventional scheduling (CS) and equivalence of sequential (SC) vs. combination adjuvant chemotherapy (CC) for node-positive breast cancer (CALGB 9741, INT C9741). [Abstract] Breast Cancer Res Treat 76 (Suppl 1): A-15, 2002. Related PublicationsMuss 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] 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] Orzano JA, Swain SM: Concepts and clinical trials of dose-dense chemotherapy for breast cancer . Clin Breast Cancer 6 (5): 402-11, 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. Trial Lead Organizations Cancer and Leukemia Group B
North Central Cancer Treatment Group
Eastern Cooperative Oncology Group
Southwest Oncology 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. |
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