Herrington 2008.

Study characteristics
Methods	Randomised, pilot, placebo‐controlled, comparative trial with 3 arms comparison of 3‐day aprepitant 125/80 mg + palonosetron + dexamethasone vs 1‐day aprepitant 125 mg + palonosetron + dexamethasone vs placebo + palonosetron + dexamethasone Patient evaluation period: June 2005 to May 2007 82 patients randomised 75 patients included Masking: double‐blind Baseline patient characteristics: reported Follow‐up: yes
Participants	Inclusion criteria 18 years of age or older with histologically or cytologically confirmed malignant disease Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 Exclusion criteria experienced an episode of emesis within 24 h before the start of chemotherapy documented primary or secondary brain neoplasm receiving radiation to abdomen or pelvis, medications with known antiemetic activity, or medications known to induce cytochrome P450 enzymes (e.g. phenytoin, carbamazepine, rifampin) Age ± SD, years: 59.6 ± 10.7 (palonosetron + 3‐day aprepitant), 58.3 ± 10.5 (palonosetron + 1‐day aprepitant), 56.1 ± 12.6 (palonosetron + placebo) Gender: male + female Tumour/cancer type: solid malignancy (breast cancer, lung cancer, head and neck cancer, other) Chemotherapy regimen highly emetogenic regimens included cisplatin ≥ 50 mg/m² breast cancer regimens included anthracycline and cyclophosphamide combinations (e.g. AC, FEC, TAC) Country: United States (single institute)
Interventions	Experimental: arm A: palonosetron + 3‐day aprepitant Day 1: aprepitant 125 mg p.o. + palonosetron 0.25 mg i.v. + dexamethasone 12 mg p.o. Days 2 to 3: aprepitant 80 mg p.o. + dexamethasone 8 mg p.o. Day 4: dexamethasone 8 mg p.o. Experimental: arm B: palonosetron + 1‐day aprepitant Day 1: aprepitant 125 mg p.o. + palonosetron 0.25 mg i.v. + dexamethasone 12 mg p.o. Days 2 to 3: matching placebo + dexamethasone 8 mg p.o. Day 4: dexamethasone 8 mg p.o. Experimental: arm C: palonosetron + placebo Day 1: placebo + palonosetron 0.25 mg i.v. + dexamethasone 18 mg p.o. Days 2 to 4: dexamethasone 8 mg p.o.
Outcomes	Primary endpoint proportion of patients with emesis in acute (Day 1) and delayed (Days 2 to 5) phases after chemotherapy Secondary endpoint(s) number of breakthrough antiemetics administered severity of nausea during the 120‐h study period complete response
Notes	"it was found that all of the patients experiencing emesis were in Arm C (n = 8 of 16 experienced emesis vs none in the other arms). Therefore, the study was temporary halted, and the protocol was amended with the removal of Arm C. The descriptive statistics of patients in Arm C will be presented, but this study group will not be included in the statistical comparison among groups" funding: "MGI Pharma and Scott & White. Grant Number: R3429" study authors did not provide disclosure of potential conflicts of interest
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: randomised trial but method of randomisation not described
Allocation concealment (selection bias)	Unclear risk	Comment: allocation concealment not reported
Blinding of participants and personnel (performance bias) Blinding of participants	Low risk	Quote: "... double‐blind ..."
Blinding of participants and personnel (performance bias) Blinding of personnel	Low risk	Quote: "... double‐blind ..."
Blinding of outcome assessment (detection bias) Subjective outcomes (Patient reported outcomes)	Low risk	Comment: both patients and personnel were blinded towards the intervention and thus had no influence on outcome assessment
Blinding of outcome assessment (detection bias) Objective outcomes (including mortality and safety)	Low risk	Comment: both patients and personnel were blinded towards the intervention and thus had no influence on outcome assessment
Incomplete outcome data (attrition bias) Subjective outcomes (Patient reported outcomes)	Low risk	Comment: all patients were included for efficacy analysis
Incomplete outcome data (attrition bias) Objective outcomes (including mortality and safety data)	Unclear risk	Quote: "there were no reports of serious adverse events that were related to study medication" Probably for all patients
Selective reporting (reporting bias)	Low risk	Comment: all outcome measures were reported in the results section
Other bias	Unclear risk	Comment: the study was temporarily halted, and the protocol was amended with removal of arm C. Descriptive statistics for patients in arm C were not included in the report