Holmes 1998.

Methods	RCT Trial Hypothesis: Antineoplastic activity of paclitaxel in metastatic breast cancer (MBC) is schedule‐dependent; infusion by 96 hr has more antineoplastic activity than by 3 hr.
Participants	Eligible patients had measurable‐evaluable MBC and usual requirements for trials. Patients were stratified by (1) doxorubicin‐sensitivity (doxorubicin‐resistant: progression during treatment for MBC or within 6 months after adjuvant doxorubicin) and (2) number of prior regimens (inclusive of adjuvant: 0 or 1 versus 2 or 3).
Interventions	Paclitaxel 250 mg/m2/3‐hr (usual premeds) or 140 mg/m2/96‐hr (no premed) repeated every 21 days. G‐CSF added only for neutropenic fever or infection then dose‐reduction.
Outcomes	Toxicity, objective response, survival
Notes	Conclusions: (1) No significant difference in overall response (OR), duration, survival. (2) OR low‐possibly due to: a) stringent OR requirements (20% MR); b) multicenter trial. (3) These data do not justify the extra logistical support required for 96‐hr infusion. Supported by grant CA 45809. Toxicity by arm reported ASCO 1996: Toxicity in 123 evaluable patients treated from March 1994 to October 1995 (data not shown). The 96‐hr arm had fewer toxic effects, but was less convenient. Trial planned accrual of 226 patients and from 1996 continued to compare the efficacy of these two schedules.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not reported
Allocation concealment (selection bias)	Low risk	"Randomized at central data management office".
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Not reported
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Unclear
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