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. 2016 May 20;2016(5):CD003139. doi: 10.1002/14651858.CD003139.pub3

WSG 2005.

Methods Randomised controlled trial
 Method of randomisation: Remotely generated, "with a random permuted block design and stratification by tumour size (<4 cm or >/=4 cm) and by centre."
Allocation concealment: Done centrally by telephone or fax
 Number of dropouts pre‐randomisation: Not stated
 Number of women randomised: 403 (201 high dose, 202 standard dose)
 Number of women analysed: 403
 Number of women not analysed: None
 Number of breaches of protocol/failure to receive prescribed treatment: High‐dose arm: 8 received no protocol therapy, 3 crossed to opposite arm, 1 was male (*see Participants), 4 had metastases, 14 had no documented radiotherapy. Control arm: 7 received no protocol treatment, 1 crossed to opposite arm, 2 had metastases, 19 had no documented radiotherapy
 Intention‐to‐treat analysis: Yes
 Number of centres: 6
 Source of funding: Amgen, Pharmacia and Lederle
 Years: 6/95 ‐ 6/02
Country: Germany
Participants INCLUDED:
 Women* with breast cancer within 6 weeks of complete resection, No metastases on CXR, liver US, bone scan. Adequate organ function performance status < 2
 18 ‐ 60 years
 At least 10 axillary nodes involved
* One man was randomised: it is unclear whether this was a breach of protocol
Interventions All women received 2 cycles of EC (cyclophosphamide 600 mg/m²; epirubicin 90 mg/m²) 2 weeks apart with GCSF priming
 Women in the high‐dose arm then received tandem EC‐thiotepa (cyclophosphamide 3000; epirubicin 90, thiotepa 400 mg/m² X 2 cycles 28 days apart) plus PBPC transplants (harvested after EC with GCSF priming)
 Women in the CDC arm had 4 further cycles of EC 2 weeks apart with GCSF priming ("dose‐intense" regimen)
 All women had radiotherapy, and postmenopausal hormone receptor‐positive women also had tamoxifen.
Outcomes Event‐free survival
 Overall survival
 Toxicity
Quality of life: European Organisation for Research and Treatment of Cancer quality‐of‐life C30 questionnaire (only administered to "about" the first 200 participants)
Notes Power calculation: 80% power to detect a 10% absolute reduction in event‐free survival after 3 years
 ASCO abstract at 34.6‐month follow‐up gives estimated survival for 2 and 4 years only. 3‐year data reported in our tables are estimated from graphs in 2003 ASCO slide presentation
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Remotely generated, with a random permuted‐block design and stratification by tumour size (<4 cm or >/=4 cm) and by centre."
Allocation concealment (selection bias) Low risk "Randomisation was done centrally by telephone or fax in the WSG study office"
Blinding (performance bias and detection bias) 
 All outcomes Unclear risk Blinding not mentioned; however this appears unlikely to influence primary review outcomes
Incomplete outcome data (attrition bias) 
 All outcomes Low risk All randomised women included in analysis
Selective reporting (reporting bias) Low risk All expected outcomes reported
Other bias Low risk No other potential bias identified

CAF = cyclophosphamide, doxorubicin & fluorouracil
 CDC = Conventional adjuvant chemotherapy
 CMF = Cyclophosphamide, Methotrexate and 5‐Fluorouracil
 CXR = chest X‐ray
 EC = epirubicin & cyclophosphamide
 EORTC = European Organisation for Research and Treatment of Cancer
 FEC = fluorouracil, epirubicin & cyclophosphamide
 GCSF = Granulocyte colony‐stimulating factor
 HDC = High‐dose chemotherapy
 LVE = Left ventricular ejection fraction (cardiac function test)
 PBPC = Peripheral blood progenitor cells
 PPC = Peripheral blood progenitor cells
 STAMP I = cyclophosphamide, cisplatin and carmustine
 STAMP V = cyclophosphamide, carboplatin and thiotepa
 US = ultrasound