Nasr 2015.

Study characteristics
Methods	Accrual: November 2008 to December 2014 Multicentre, 4 centres Phase of trial: 3 Study design: RCT Country or countries where the trial was conducted: Egypt Median follow‐up: 52 months
Participants	Age: mean 46, 95% confidence interval 32 to 62 years Nodal status of breast cancer: 94% node positive, 6% node negative Adjuvant or neoadjuvant: adjuvant Notable exclusion criteria: none
Interventions	Arm 1: 5‐fluorouracil 500 mg/m2 + epirubicin 100 mg/m2 + cyclophosphamide 500 mg/m2 every 3 weeks for 3 cycles then docetaxel 80 mg/m2 + carboplatin AUC5 every 3 weeks for 3 cycles, followed by postoperative radiotherapy, followed by oral cyclophosphamide 50 mg daily, and methotrexate 2.5 mg orally twice daily on days 1, 2 of each week every 28 days for 1 year Arm 2: 5‐fluorouracil 500 mg/m2 + epirubicin 100 mg/m2 + cyclophosphamide 500 mg/m2 every 3 weeks for 3 cycles then docetaxel 100 mg/m2 every 3 weeks for 3 cycles Note: intervention is addition of carboplatin AND 12 months of metronomic chemotherapy
Outcomes	Primary DFS, defined as the time of randomisation until relapse, recurrence or the last follow‐up visit OS, defined as the time of randomisation until death or the last follow‐up visit Secondary Toxicity, assessed according to NCI CTC version 2.0. Early toxicity includes toxicities during treatment and up until 8 weeks after treatment; late toxicity includes toxicities following 8 weeks after treatment Treatment discontinuation, delays and dose reductions reported
Notes	No trial registration record identified in the World Health Organization International Clinical Trials Registry Platform. All randomised participants were included as intention‐to‐treat analysis for all outcomes. Note: none of the efficacy or safety outcome data (in tables or figures) presented the denominators. Study did not report assessing the proportional hazards assumption. For DFS and OS, we estimated the hazard ratio using Tierney's method. Funding considerations: not reported.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Patients were randomly assigned to one of [two] groups." (p.3) No further details were provided.
Allocation concealment (selection bias)	Unclear risk	No description whether randomisation was centralised, although probably done as involved randomisation across multiple sites.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Participants and personnel were aware of treatment allocation. This may have been associated with some performance bias but it was not judged to be of serious concern given types of outcomes collected.
Blinding of outcome assessment (detection bias): DFS	Low risk	Lack of blinding unlikely to influence this outcome.
Blinding of outcome assessment (detection bias): OS	Low risk	Lack of blinding unlikely to influence this outcome.
Blinding of outcome assessment (detection bias): toxicity	Low risk	Toxicity outcomes graded using the CTCAE. Although the study was open‐label, grading symptoms using the CTCAE is standardised and, therefore, knowing treatment allocation may have had minimal effect on the grading of outcomes.
Selective reporting (reporting bias)	Unclear risk	Prespecified outcome measures including DFS and OS were reported. However, limited data were provided and the OS Kaplan‐Meier curve was difficult to interpret.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Paper indicated that all randomised participants were included in analysis. Number of participants who did not receive treatment were equal across treatment arms (i.e. 3 participants in each).
Other bias	Low risk	None identified.