Figg 2005.

Study characteristics
Methods	Recruitment period: not reported Outcomes: overall survival, disease progression, adverse events Pain assessment tool: not reported Randomization: intervention vs control
Participants	Eligibility criteria: men with castration‐resistant prostate adenocarcinoma metastatic to bone and progression after combined androgen blockade and antiandrogen withdrawal ECOG performance status ≤ 2 increasing prostate‐specific antigen despite continued testicular suppression or progression on computer tomographie (CT)/bone scan, or both Exclusion criteria: not reported Participants randomized: 72 randomized, 36 intervention, 36 control Mean age: intervention: 72 years control: 70 years Country of participants: not clearly reported
Interventions	Previous interventions: majority of participants received second‐line hormonal therapy 15 participants received chemotherapy Interventions during study period: intervention: alendronate 40 mg daily, ketoconazole 1200 mg daily (dose reduction of alendronate and ketoconazole in participants with drug toxicity), hydrocortisone 30 mg daily control: ketoconazole 1200 mg daily (dose reduction of ketoconazole in participants with drug toxicity), hydrocortisone 30 mg daily
Outcomes	Reported and analyzed in this review: overall survival adverse events (fatigue, diarrhea, nausea)
Funding sources	Funding sources: support from the National Cancer Institute (USA)
Declarations of interest	Conflicts of interest: not reported
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information on sequence generation
Allocation concealment (selection bias)	Unclear risk	Insufficient information on allocation concealment
Blinding of participants and personnel (performance bias) Blinding of participants	High risk	“This was an open label, randomized, phase II study [...]”
Blinding of participants and personnel (performance bias) Blinding of personnel	High risk	“This was an open label, randomized, phase II study [...]”
Blinding of outcome assessment (detection bias) Outcomes subjective to participants	High risk	“This was an open label, randomized, phase II study [...]”
Blinding of outcome assessment (detection bias) Outcomes subjective to outcome assessors	Unclear risk	No information on blinding of outcome assessor
Blinding of outcome assessment (detection bias) Objective outcomes	Low risk	No information on blinding of outcome assessor, but no known reason for bias
Incomplete outcome data (attrition bias) Time‐to‐event data	Low risk	"The primary analysis was conducted on all patients who were randomized"
Incomplete outcome data (attrition bias) Safety data	Low risk	"Safety analyses were performed on randomized patients who received at least 1 dose of investigational drug"
Incomplete outcome data (attrition bias) Other outcomes	Low risk	Complete analysis of all randomized participants
Selective reporting (reporting bias)	Unclear risk	Protocol available (NCT00019695); more outcomes reported than prespecified in the protocol (e.g. overall survival).
Other bias	Low risk	None identified