Nabholtz JM 1999.

Study characteristics
Methods	Accrual (July 1994 ‐ February 1997) RCT‐ Phase III Randomisation centralised ‐ block design by institution ‐ no stratification by characteristics ‐ non blinded, Canadian multicentre Groups well balanced for pre‐treatment characteristics
Participants	392 women over the age of 18 with histologically or cytologically proven metastatic progressive adenocarcinoma of the breast and measurable or non measurable but assessable disease 100% MBC 38% Firstline All participants previously treated with anthrycycline CT for advanced disease or disease progression within 12 months of the end of anthrycycline therapy given as adjuvant treatment. Excluded if pretreated with mitomycin, vinca alkaloids or taxoids Randomised no: 1) n = 203 (median age 51; 30‐73)) 2) 189 (median age 52;32‐78)) Assessable no: 1) n = 200 2) n = 187
Interventions	TXT vs MMC +V2 1) Docetaxel 100 mg/m2 iv every 3 weeks 2) Mitomycin 12 mg/m2 iv every 6 wks + Vinblastine 6 mg/m2 iv every 3 wks Maximum 10 treatment cycles
Outcomes	Survival and TTP curves included ‐ Kaplan‐Meier method ‐ TTP from date of randomisation TTF curve excluded Median survival 1) 11.4 mths 2) 8.7 mths Median TTP 1) 19 weeks 2) 11 weeks OR (CR+PR) 1) 59/179 2) 21/171 Toxicity WHO 3‐4 Nausea and vomiting 1) 14/200 2) 9/187 Neutropenia 1) 188/200 2) 176/187 Toxic death 1) 4/203 (sepsis, pneumonia, unspecified infection, unexplained respiratory failure) 2) 3/189 (hemolytic uremia, progressive lymphangitic carcinomatosis) QOL ‐ EORTC QLQ‐C30
Notes	F/U survival and TTP min 4.5 mths ‐ max 33mths (from curve) ITT ‐ 5 patients who did not receive treatment (3;2) were included in the efficacy analysis, including survival. Analysis of response and TTP was also done on eligible and assessable population
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation centralised using a block design by institution
Allocation concealment (selection bias)	Low risk	Centrally randomised
Incomplete outcome data (attrition bias) All outcomes	Low risk	Missing data balanced across groups
Selective reporting (reporting bias)	Low risk	All expected outcomes reported