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 |
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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 |
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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) |
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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