Burlage 2008.
| Methods | Location: the Netherlands Number of centres: 2 Date of enrolment: April 1999 ‐ October 2003 |
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| Participants | Inclusion criteria: biopsy confirmed HNSCC, initial 5% (wt/vol) citric acid‐stimulated parotid salivary flow > 0.1 mL/min Exclusion criteria: previous irradiation and/or previous or concurrent chemotherapy, patients with salivary gland tumours, severe cardiovascular disease or chronic obstructive pulmonary disease, pregnant women Age: pilocarpine: 18‐60 years 50 participants, > 60 years 35 participants; placebo: 18‐60 years 42 participants, > 60 years 42 participants Gender (M:F): pilocarpine 22:63; placebo 13:71 Cancer type: oral cavity (17%), oropharynx (18%), larynx (51%), hypopharynx (7%), nasopharynx (4%), unknown primary (1%) (equally distributed across groups) Submandibular gland removal: both removed: pilocarpine 2%, placebo 5%; 1 removed: pilocarpine 37%, placebo 38% Radiotherapy: clinical target volume of initial field encompassed the primary tumour site with 1.5 cm margin, neck node levels in which pathologic nodes were found and elective node areas on both sides. Conventional fractionation schedule. Received at least 40 Gy in daily 2 Gy fractions Chemotherapy: none Number randomised: 170 (85 per group) Number evaluated: 113 (pilocarpine 55, placebo 58) |
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| Interventions |
Pilocarpine versus placebo Pilocarpine: 5 mg 4 times daily 2 days before start of RT until 14 days after RT Placebo: similar tablets, same schedule |
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| Outcomes | Xerostomia: from validated head‐and‐neck symptom questionnaire on 5‐point scale; LENT SOMA Salivary flow rates: parotid salivary flow using Carlson‐Crittenden cups, from left and right hand parotid glands simultaneously under standardised conditions for 10 min. Flow stimulated with 5% (wt/vol) citric acid. Parotid flow complication probability also reported Adverse effects: not reported Survival data: locoregional control Other oral symptoms: eating, swallowing Other oral signs: not reported Quality of life: some covered in validated head‐and‐neck symptom questionnaire on 5‐point scale Patient satisfaction: not reported Cost data: not reported Timing of assessment: before RT, 6 weeks, 6 months and 12 months postRT |
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| Funding | Not reported. Conflicts of interest: "none" reported | |
| Trial registration | Not registered | |
| Sample size calculation presented | Yes | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "Randomisation was executed by the hospital pharmacist by computer, using random permuted blocks within strata. The randomisation key was opened after the last saliva collection (1 year after the last patient was included and after completion of all planned assessments)" |
| Allocation concealment (selection bias) | Low risk | See above |
| Blinding (performance bias and detection bias) patients/carers | Low risk | Quote: "Double‐blind randomised placebo‐controlled study". Intervention was tablets supplied by the pharmacy |
| Blinding (performance bias and detection bias) outcome assessment | Low risk | Quote: "Double‐blind randomised placebo‐controlled study". Intervention was tablets supplied by the pharmacy |
| Incomplete outcome data (attrition bias) All outcomes | High risk | 32% missing at 12 months with no clear reasons given by study group |
| Selective reporting (reporting bias) | High risk | Adverse events and xerostomia data not fully reported |
| Other bias | Low risk | No other sources of bias are apparent |