Low-Dose Oral Cyclophosphamide and Methotrexate Maintenance for Hormone Receptor-Negative Early Breast Cancer: International Breast Cancer Study Group Trial 22-00

被引：60

作者：

Colleoni, Marco ^{[1
]}

Gray, Kathryn P. ^{[7
,8
,9
]}

Gelber, Shari ^{[7
,8
]}

Lang, Istvan ^{[12
]}

Thurlimann, Beat ^{[13
,14
]}

Gianni, Lorenzo ^{[3
]}

Abdi, Ehtesham A. ^{[17
,18
,19
]}

Gomez, Henry L. ^{[25
]}

Linderholm, Barbro K. ^{[26
,27
]}

Puglisi, Fabio ^{[4
]}

Tondini, Carlo ^{[5
]}

Kralidis, Elena ^{[14
,15
]}

Eniu, Alexandru ^{[28
]}

Cagossi, Katia ^{[6
]}

Rauch, Daniel ^{[14
,16
]}

Chirgwin, Jacquie ^{[19
,20
,21
,22
]}

Gelber, Richard D. ^{[7
,8
,9
,10
,11
]}

Regan, Meredith M. ^{[7
,8
,10
]}

Coates, Alan S. ^{[23
,24
]}

Price, Karen N. ^{[7
,11
]}

Viale, Giuseppe ^{[1
,2
]}

Goldhirsch, Aron ^{[1
]}

机构：

[1] European Inst Oncol, Milan, Italy

[2] Univ Milan, Milan, Italy

[3] Osped Infermi, Rimini, Italy

[4] Univ Udine, Univ Hosp Udine, Udine, Italy

[5] Osp Papa Giovanni XXIII, Bergamo, Italy

[6] Osped Carpi, Carpi, Italy

[7] Int Breast Canc Study Grp, Stat Ctr, Boston, MA USA

[8] Dana Farber Canc Inst, Boston, MA USA

[9] Harvard TH Chan Sch Publ Hlth, Boston, MA USA

[10] Harvard Med Sch, Boston, MA USA

[11] Frontier Sci & Technol Fdn, Boston, MA USA

[12] Natl Inst Oncol, Budapest, Hungary

[13] Kantonsspital, St Gallen, Switzerland

[14] Swiss Grp Clin Canc Res, Bern, Switzerland

[15] Kantonsspital Aarau, Aarau, Switzerland

[16] Spital Thun, Thun, Switzerland

[17] Tweed Head Hosp, Tweed Heads, NSW, Australia

[18] Griffith Univ, Southport, Qld, Australia

[19] Australia & New Zealand Breast Canc Trials Grp, Newcastle, NSW, Australia

[20] Box Hill Hosp, Box Hill, Vic, Australia

[21] Maroondah Hosp, Ringwood, Vic, Australia

[22] Monash Univ, Melbourne, Vic, Australia

[23] Int Breast Canc Study Grp, Sydney, NSW, Australia

[24] Univ Sydney, Sch Publ Hlth, Sydney, NSW, Australia

[25] Inst Nacl Enfermedades Neoplas, Lima, Peru

[26] Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Gothenburg, Sweden

[27] Sahlgrens Univ Hosp, Gothenburg, Sweden

[28] Canc Inst Ion Chiricuta, Cluj Napoca, Romania

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2016年 / 34卷 / 28期

关键词：

ADJUVANT CHEMOTHERAPY; ANTITUMOR-ACTIVITY; RANDOMIZED-TRIAL; THERAPY; ANGIOGENESIS; TRASTUZUMAB; BEVACIZUMAB; RECURRENCE; MANAGEMENT; PLUS;

D O I：

10.1200/JCO.2015.65.6595

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose To evaluate the benefit of low-dose cyclophosphamide and methotrexate (CM) maintenance, which previously demonstrated antitumor activity and few adverse effects in advanced breast cancer, in early breast cancer. Patients and Methods International Breast Cancer Study Group (IBCSG) Trial 22-00, a randomized phase III clinical trial, enrolled 1,086 women (1,081 intent-to-treat) from November 2000 to December 2012. Women with estrogen receptor- and progesterone receptor-negative (< 10% positive cells by immunohistochemistry) early breast cancer any nodal and human epidermal growth factor receptor 2 status, were randomly assigned anytime between primary surgery and 56 days after the first day of last course of adjuvant chemotherapy to CM maintenance (cyclophosphamide 50 mg/day orally continuously and methotrexate 2.5 mg twice/day orally on days 1 and 2 of every week for 1 year) or to no CM. The primary end point was disease-free survival (DFS), which included invasive recurrences, second (breast and nonbreast) malignancies, and deaths. Results After a median of 6.9 years of follow-up, DFS was not significantly better for patients assigned to CM maintenance compared with patients assigned to no CM, both overall (hazard ratio [HR], 0.84; 95% CI, 0.66 to 1.06;P = .14) and in triple-negative (TN) disease (n = 814; HR, 0.80; 95% CI, 0.60 to 1.06). Patients with TN, node-positive disease had a nonstatistically significant reduced HR (n = 340; HR, 0.72; 95% CI, 0.49 to 1.05). Seventy-one (13%) of 542 patients assigned to CM maintenance did not start CM. Of 473 patients who received at least one CM maintenance dose (including two patients assigned to no CM), 64 (14%) experienced a grade 3 or 4 treatment-related adverse event; elevated serum transaminases was the most frequently reported (7%), followed by leukopenia (2%). Conclusion CM maintenance did not produce a significant reduction in DFS events in hormone receptor-negative early breast cancer. The trend toward benefit observed in the TN, node-positive subgroup supports additional exploration of this strategy in the TN, higher-risk population. (C) 2016 by American Society of Clinical Oncology.

引用

页码：3400 / +

页数：11

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