PREPARE trial: A randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel and CMF versus a standard-dosed epirubicin/cyclophosphamide followed by paclitaxel ± darbepoetin alfa in primary breast cancer-results at the time of surgery

Annals of Oncology

Volumn 22, Issue 9, 2011, Pages 1988-1998

  Untch, M ^a   Fasching, P A ^b   Konecny, G E ^c   von Koch, F ^d   Conrad, U ^e   Fett, W ^f   Kurzeder, C ^g   Luck H J ^h   Stickeler, E ⁱ   Urbaczyk, H ^j   Liedtke, B ^k   Salat, C ^l   Harbeck, N ^m   Muller V ⁿ   Schmidt, M ^o   Hasmuller S ^d   Lenhard, M ^d   Schuster, T ^p   Nekljudova, V ^q   Lebeau, A ⁿ   Loibl, S ^q   von Minckwitz, G ^q   more..

^a HELIOS KLINIKUM BERLIN BUCH   (Germany)

^b UNIVERSITY HOSPITAL ERLANGEN   (Germany)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^e St Barbara Hospital   (Germany)

^f Hematologic/Oncologic Clinic   (Germany)

^g UNIVERSITY HOSPITAL ULM   (Germany)

^h HANNOVER MEDICAL SCHOOL   (Germany)

ⁱ UNIVERSITY OF FREIBURG   (Germany)

^j KLINIKUM KASSEL   (Germany)

^k Department of Obstetrics and Gynecology   (Germany)

^l Center for Hematology and Oncology   (Germany)

^m TECHNICAL UNIVERSITY OF MUNICH   (Germany)

ⁿ UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

^o UNIVERSITY MEDICAL CENTER MAINZ   (Germany)

^p TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^q German Breast Group   (Germany)

more..

Author keywords

Darbepoetin alfa; Dose dense chemotherapy; Dose intensified chemotherapy; Neoadjuvant chemotherapy; Pathological complete response; Primary breast cancer

Indexed keywords

CYCLOPHOSPHAMIDE; EPIRUBICIN; FLUOROURACIL; HEMOGLOBIN; HORMONE RECEPTOR; METHOTREXATE; NOVEL ERYTHROPOIESIS STIMULATING PROTEIN; PACLITAXEL; RECOMBINANT GRANULOCYTE COLONY STIMULATING FACTOR;

ADULT; AGED; ANEMIA; ARTICLE; BREAST CANCER; CANCER ADJUVANT THERAPY; CANCER GRADING; CHEMOTHERAPY INDUCED EMESIS; CONGESTIVE HEART FAILURE; CONTROLLED STUDY; DERMATITIS; DIARRHEA; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG FATALITY; DRUG FEVER; DRUG WITHDRAWAL; HUMAN; LEUKOPENIA; MAJOR CLINICAL STUDY; MUCOSA INFLAMMATION; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUROLOGIC DISEASE; NEUTROPENIA; PARTIAL MASTECTOMY; PATIENT COMPLIANCE; PHASE 3 CLINICAL TRIAL; PREOPERATIVE CARE; PRIORITY JOURNAL; PROCTITIS; PROSPECTIVE STUDY; RANDOMIZED CONTROLLED TRIAL; SENSORY NEUROPATHY; STOMATITIS; THROMBOCYTOPENIA; THROMBOEMBOLISM; TREATMENT RESPONSE;

EID: 80052414508     PISSN: 09237534     EISSN: 15698041     Source Type: Journal    
DOI: 10.1093/annonc/mdq709     Document Type: Article

References (36)

1. Kaufmann M, von Minckwitz G, Bear HD et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives 2006. Ann Oncol 2007; 18: 1927-1934.
2. Kaufmann M, Hortobagyi GN, Goldhirsch A et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update. J Clin Oncol 2006; 24: 1940-1949.
3. von Minckwitz G, Raab G, Caputo A et al. Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group. J Clin Oncol 2005; 23: 2676-2685.
4. Gralow JR, Burstein HJ, Wood W et al. Preoperative therapy in invasive breast cancer: pathologic assessment and systemic therapy issues in operable disease. J Clin Oncol 2008; 26: 814-819.
5. Mauri D, Pavlidis N, Ioannidis JP. Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst 2005; 97: 188-194.
6. 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 2003; 21: 976-983.
7. Tusquets I, Estévez LG, Alvarez I et al. The use of taxanes in the neoadjuvant treatment of breast cancer: a review of randomized phase II/III trials. Clin Breast Cancer 2007; 7: 764-774.
8. Mazouni C, Kau SW, Frye D et al. Inclusion of taxanes, particularly weekly paclitaxel, in preoperative chemotherapy improves pathologic complete response rate in estrogen receptor-positive breast cancers. Ann Oncol 2007; 18: 874-880.
9. Untch M, Möbus V, Kuhn W et al. Intensive dose-dense compared with conventionally scheduled preoperative chemotherapy for high-risk primary breast cancer. J Clin Oncol 2009; 27: 2938-2945.
10. Ellis GK, Green SJ, Russell CA et al. SWOG 0012, a randomized phase III comparison of standard doxorubicin (A) and cyclophosphamide (C) followed by weekly paclitaxel (T) versus weekly doxorubicin and daily oral cyclophosphamide plus G-CSF (G) followed by weekly paclitaxel as neoadjuvant therapy for inflammatory and locally advanced breast cancer. J Clin Oncol 2006; 24: 18S (Abstr LBA537). ASCO Ann Meeting Proc Part I.
11. 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 2003; 21: 1431-1439.
12. Möbus VJ, Jackisch C, Lück HJ et al. Intense dose-dense sequential chemotherapy with epirubicin, paclitaxel, and cyclophosphamide compared with conventionally scheduled chemotherapy in high-risk primary breast cancer patients. Mature results of an AGO-phase III study. J Clin Oncol 2010; 28: 2876-2880.
13. Aapro MS, Cameron DA, Pettengell R et al. EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapyinduced febrile neutropenia in adult patients with lymphomas and solid tumours. Eur J Cancer 2006; 42: 2433-2453.
14. von Minckwitz G, Kümmel S, du Bois A et al. Pegfilgrastim 6 ciprofloxacin for primary prophylaxis with TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy for breast cancer. Results from the GEPARTRIO Study. Ann Oncol 2008; 19: 292-298.
15. Teicher BA, Holden SA, Menon K et al. Effect of hemoglobin solution on the response of intracranial and subcutaneous 9L tumors to antitumor alkylating agents. Cancer Chemother Pharmacol 1993; 33: 57-62.
16. Littlewood TJ, Bajetta E, Nortier JWR et al. Effects of epoetin alfa on hematologic parameters and quality of live in cancer patients receiving nonplatinum chemotherapy: results of a randomized, double-blind, placebo-controlled trial. J Clin Oncol 2001; 19: 2865-2874.
17. Loibl S, Kaufmann M, Maataoui V et al. Darbepoetin alfa as primary prophylaxis of anemia in patients with breast cancer treated preoperatively with docetaxel/doxorubicin/cyclophosphamide. Support Cancer Ther 2006; 3: 103-109.
18. Rizzo JD, Somerfield MR, Hagerty KL et al. Use of epoetin and darbepoetin in patients with cancer: 2007 American Society of Clinical Oncology/American Society of Hematology clinical practice guideline update. J Clin Oncol 2008; 26: 132-149.
19. Bonadonna G, Valagussa P, Moliterni A et al. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up. N Engl J Med 1995; 332: 901-906.
20. Bonadonna G, Valagussa P, Brambilla C et al. Primary chemotherapy in operable breast cancer: eight- experience at the Milan Cancer Institute. J Clin Oncol 1998; 16: 93-100.
21. Bear HD, Anderson S, Smith RE et al. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer. National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 2006; 24: 2019-2027.
22. Steger GG, Galid A, Gnant M et al. Pathologic complete response with six compared with three cycles of neoadjuvant epirubicin plus docetaxel and granulocyte colony-stimulating factor in operable breast cancer: results of ABCSG-14. J Clin Oncol 2007; 25: 2012-2018.
23. Untch M, von Minckwitz G, Konecny G et al. PREPARE trial. A randomized phase III trial comparing preoperative, dose-dense, dose intensified chemotherapy with epirubicin, paclitaxel and CMF versus a standard dosed epirubicin / cyclophosphamide followed by paclitaxel 6 darbepoetin alfa in primary breast cancer-long term results. Ann Oncol 2011; 22: 1999-2006.
24. Sinn HP, Schmid H, Junkermann H et al. Histologic regression of breast cancer after primary (neoadjuvant) chemotherapy. Geburtshilfe Frauenheilkd 1994; 54: 552-558.
25. von Minckwitz G, Kümmel S, Vogel P et al. Intensified neoadjuvant chemotherapy in early-responding breast cancer: phase III randomized GeparTrio study. J Natl Cancer Inst 2008; 100: 552-562.
26. von Minckwitz G, Untch M, Nüsch E et al. Impact of treatment characteristics on response of different breast cancer subtypes: pooled multilayer analysis of the German neoadjuvant chemotherapy trials. J Clin Oncol 2010; 28 (Suppl): 15s (Abstr 501).
27. Loibl S, von Minckwitz G, Raab G et al. Surgical procedures after neoadjuvant chemotherapy in operable breast cancer: results of the GEPARDUO trial. Ann Surg Oncol 2006; 13: 1434-1442.
28. Yardley DA, Burris HA 3rd, Farley CP et al. A phase II feasibility trial of dose-dense docetaxel followed by doxorubicin/cyclophosphamide as adjuvant or neoadjuvant treatment for women with node-positive or high-risk node-negative breast cancer. Clin Breast Cancer 2008; 8: 242-248.
29. Burdette-Radoux S, Wood ME, Olin JJ et al. Phase I/II trial of adjuvant dose-dense docetaxel/epirubicin/cyclophosphamide (TEC) in stage II and III breast cancer. Breast J 2007; 13: 274-280.
30. Leyland-Jones B, Semiglazov V, Pawlicki M et al. Maintaining normal hemoglobin levels with epoetin alfa in mainly nonanemic patients with metastatic breast cancer receiving first-line chemotherapy: a survival study. J Clin Oncol 2005; 23: 5960-5972.
31. Möbus V, Lück H, Thomssen C et al. The impact of epoetin-alpha on anemia, red blood cell (RBC) transfusions, and survival in breast cancer patients (pts) treated with dose-dense sequential chemotherapy: mature results of an AGO phase III study (ETC trial) ASCO Annual Meeting, 2007. J Clin Oncol 2007; 25 (Suppl): 18S (Abstr 569).
32. Bennett CL, Silver SM, Djulbegovic B et al. Venous thromboembolism and mortality associated with recombinant erythropoietin and darbepoetin administration for the treatment of cancer-associated anemia. JAMA 2008; 299: 914-924.
33. Sparano JA, Wang M, Martino S et al. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med 2008; 358(16): 1663-1671.
34. von Minckwitz G, Kümmel S, Vogel P et al. Neoadjuvant vinorelbine-capecitabine versus docetaxel-doxorubicin-cyclophosphamide in early nonresponsive breast cancer: phase III randomized GeparTrio trial. J Natl Cancer Inst 2008; 100: 542-551.
35. Hennessy BT, Hortobagyi GN, Rouzier R et al. Outcome after pathologic complete eradication of cytologically proven breast cancer axillary node metastases following primary chemotherapy. J Clin Oncol 2005; 23: 9304-9311.
36. Mazouni C, Peintinger F, Wan-Kau S et al. Residual ductal carcinoma in situ in patients with complete eradication of invasive breast cancer after neoadjuvant chemotherapy does not adversely affect patient outcome. J Clin Oncol 2007; 25: 2650-2655.