Smith 1999.

Methods	RCT.
Participants	563 patients with metastatic or locally advanced breast cancer Age at entry in the trial was as follows: <= 49 years: 197 (35%), >= 50 years: 366 (65%). There were 349 (62%) women with a normal performance status and 214 (38%) with a symptomatic status. Disease stage was as follows: IIIB: 92 (16%), IV: 471 (84%).
Interventions	High dose single agent paclitaxel (250 mg/ m2). 3 versus 24 hour infusion.
Outcomes	Primary and overall tumour response, event‐free survival (progressive disease, relapse or death), survival, toxicity, compliance.
Notes	Patients receiving the longer duration infusion were given prophylactic G‐CSF in an attempt to reduce the risk of infection in patients with a low granulocyte count. Patients receiving the shorter infusion of paclitaxel only received G‐CSF if they had such an episode of infection. 176/278 women died in the 3 hour infusion group and 184/282 women died in the 24 hour infusion group. 241/278 women either had progressive disease, relapsed or died in the 3 hour infusion group compared to 251/282 women in the 24 hour infusion group. Median time to death was 21.1 months (18.2‐24.2 months) and 21.9 (19.6 to 23.6 months) months in the 3 hour and 24 hour infusion groups respectively. Median time to first event was 6.3 months (5.4‐7.4 months) and 7.2 (6.1 to 8.3 months) months in the 3 hour and 24 hour infusion groups respectively. None of these differences were statistically significant, even when adjusted for prognostic variables (survival P = 0.96 and event‐free survival P = 0.95). The primary tumour response rates were 41% for the three hour infusion and 51% for the 24 hour infusion (P = 0.03 and P = 0.02 when adjusted for significant factors in a logistic regression analysis). The figures for overall responses were 44% for the three hour infusion and 54% for the 24 hour infusion (unadjusted P value = 0.02 and adjusted P = 0.02). There were 11 deaths due to adverse events (10 in the first four cycles), a number of which were due to infection. Seven of these were in patients receiving the three hour infusion and four with the 24 hour infusion.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not reported
Allocation concealment (selection bias)	Unclear risk	Not reported
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Not reported
Incomplete outcome data (attrition bias) All outcomes	Low risk	3 hr infusion: 258/279 (92%) patients were assessable for primary tumour response, 261/279 (94%) patients for overall tumour response and 278/279 (99%) patients were assessed for progression‐free survival, overall survival and toxicity. 24 hr infusion: 255/284 (90%) patients were assessable for primary tumour response, 259/284 (91%) patients for overall tumour response and 282/284 (99%) patients were assessed for progression‐free and overall survival. 279/284 (98%) patients were assessed for toxicity.
Selective reporting (reporting bias)	Unclear risk	Insufficient information to permit judgement
Other bias	Unclear risk	Insufficient information to assess whether an important risk of bias exists