Skip to main content
. 2021 Nov 16;2021(11):CD012775. doi: 10.1002/14651858.CD012775.pub2

Hesketh 2003.

Study characteristics
Methods Randomised, placebo‐controlled trial with 2 arms

  • comparison of aprepitant 125/80 + ondansetron + dexamethasone vs placebo + ondansetron + dexamethasone


Recruitment period: n.r.

  • 562 patients screened

  • 530 patients randomised

  • 521 patients (260 patients in the aprepitant group and 261 patients in the standard therapy group) included in the efficacy analysis


Masking: double‐blind
Baseline patient characteristics: reported
Follow‐up: n.r.
Participants Inclusion criteria

  • cisplatin‐naïve patients ≥ 18 years old

  • Karnofsky score ≥ 60

  • scheduled to receive first cycle of chemotherapy including cisplatin ≥ 70 mg/m²

  • female patients of childbearing potential required to have a negative beta human chorionic gonadotropin test result


Exclusion criteria

  • use of illicit drugs or signs of current alcohol abuse

  • abnormal laboratory values (including WBC < 3000/mm³ and absolute neutrophil count < 1500/mm³, platelet count < 100,000/mm³, AST > 2.5 × ULN, ALT > 2.5 × ULN, bilirubin > 1.5 × ULN, or creatinine > 1.5 × ULN)

  • uncontrolled disease for which, in the opinion of the investigator, the patient should be excluded for safety reasons

  • multiple‐day cisplatin‐based chemotherapy in a single cycle

  • radiation therapy to abdomen or pelvis within 1 week before study Day 1 or between Days 1 and 6


Mean age (range) ± SD, years: 59 (18 to 84) ± 12, aprepitant 125/80 regimen; 58 (19 to 83) ± 12, placebo group
Gender: male + female
Tumour/cancer type: solid malignancy (respiratory cancer, urogenital cancer, others)
Chemotherapy regimen: cisplatin ≥ 70 mg/m²
Country: 15 centres in United States, 14 centres in other countries
Interventions Experimental: arm A: aprepitant 125/80
Day 1: p.o. aprepitant 125 mg + i.v. ondansetron 32 mg + p.o. dexamethasone 12 mg
Days 2 to 3: p.o. aprepitant 80 mg + p.o. dexamethasone 8 mg
Day 4: p.o. dexamethasone 8 mg
Standard therapy: arm B
Day 1: i.v. ondansetron 32 mg + p.o. dexamethasone 20 mg
Days 2 to 4: p.o. dexamethasone 8 mg twice per day
Outcomes Primary endpoint

  • proportion of patients with complete response (no emetic episodes and no rescue therapy (i.e. medication taken for established nausea or vomiting) overall (Days 1 to 5))


Secondary endpoints

  • no emesis

  • no use of rescue therapy

  • complete protection (no emesis, no rescue therapy, no significant nausea (VAS score < 25 mm))

  • total control (no emesis, no rescue therapy, no nausea (VAS score < 5 mm))

  • impact of CINV on daily life (as measured by FLIE total score > 108)

  • no nausea (VAS score < 5 mm)

  • no significant nausea (VAS score < 25 mm)
Notes

  • "this study was funded by Merck Research Laboratories, Whitehouse Station, NJ"

  • "the sponsor managed the data and performed the analyses for this study"

  • "no conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. Owns stock: Alexandra D. Carides, Merck; Scott Reines, Merck; Judith K. Evans, Merck; Klaus Beck, Merck; Kevin J. Horgan, Merck. Acted as a consultant within the last 2 years: Paul J. Hesketh, Merck; Steven M. Grunberg, Merck; Ronald de Wit, Merck; Richard J. Gralla, Merck; Fausto Roila, Merck; David G. Warr, Merck; Sant P. Chawla, Merck. Performed contract work within the last 2 years: Paul J. Hesketh, Merck; Steven M. Grunberg, Merck; Ronald de Wit, Merck; Richard J. Gralla, Merck; Fausto Roila, Merck; David G. Warr, Merck; Sant P. Chawla, Merck. Received more than $2,000 a year from a company for either of the last 2 years: Paul J. Hesketh, Merck; Steven M. Grunberg, Merck; Ronald de Wit, Merck; Richard J. Gralla, Merck; Fausto Roila, Merck; Scott Reines, Merck; Mary E. Elmer, Merck; Judith K. Evans, Merck; Alexandra D. Carides, Merck; Juliana Ianus, Merck; Kevin J. Horgan, Merck"

  • 052 study group
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Quote: "... computer‐generated random assignment schedule ..."
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 (e.g. hiccups)
Incomplete outcome data (attrition bias)
Subjective outcomes (Patient reported outcomes) Low risk Comment: a modified intent‐to‐treat approach, which included all patients who received cisplatin, took study drug, and had at least 1 post‐treatment assessment, was used to analyse the data
Incomplete outcome data (attrition bias)
Objective outcomes (including mortality and safety data) Low risk Quote: "all patients who received cisplatin and at least one dose of study drug were included in the statistical analyses for safety"
Selective reporting (reporting bias) Low risk Comment: all outcome measures were reported in the results section
Other bias Low risk Comment: no information to suggest other sources of bias