Postmus 1992.

Methods	STUDY DESIGN: Parallel study LOCATION, NUMBER OF CENTRES: Multicentre DURATION OF STUDY: April 1986 to June 1987 CONCEALMENT OF ALLOCATION: D DESCRIBED AS RANDOMISED: Yes DESCRIBED AS DOUBLE BLIND: No METHOD OF RANDOMISATION WELL‐DESCRIBED/APPROPRIATE: Not described METHOD OF BLINDING WELL‐DESCRIBED/APPROPRIATE: Not described DESCRIPTION OF WITHDRAWALS/DROP‐OUTS: Not described GRADE ASSESSMENT QUALITY RATING: Low TYPE OF ANALYSIS (AVAILABLE CASE/TREATMENT RECEIVED/ ITT): ITT
Participants	ELIGIBILITY INCLUSION CRITERIA: Newly diagnosed patients with histologically or cytologically proven SCLC; no previous chemotherapy; normal renal function (creatinine clearance > 60 ml/min); normal bilirubin (< 25 µmol/L); ECOG performance score <= 3; age <= 70 years; normal number of leukocytes (> 3.0 x 109/L) and platelets (> 100 x 109/L). In the case of bone marrow metastases, all values of leukocytes and platelets were acceptable. Informed consent was obtained from all patients. EXCLUSION CRITERIA: N RANDOMISED: 178 (CDE ‐ 63; IMP ‐ 55; VP ‐ 60) ASSESS STAGE: Yes (N LIMITED): 78 (N EXTENSIVE): 100 M: 142 F: 36 AGE: median: CDE ‐ 59; IMP ‐ 59; VP ‐ 57 (range: CDE ‐ 39 to 70; IMP ‐ 38 to 69; VP ‐ 39 to 70)
Interventions	TYPE: Chemotherapy REGIMENS: CDE ‐ cyclophosphamide 1 g/m2 IV on day 1, doxorubicin 45 mg/m2 IV on day 1, and etoposide 100 mg/m2 IV on days 1, 3 and 5. Maximally 5 courses were given at 3‐week intervals between courses. IMP ‐ carboplatin 400 mg/m2 dissolved in 250 ml dextrose 5% and given as a 30 min IV infusion, and ifosfamide 5 g/m2 given as a 24‐hour infusion. Mesna 0.6 g/m2 was given as an IV bolus with 200 ml mannitol (20%) before the ifosfamide infusion. During the ifosfamide infusion and the following 12 hours 3.75 g/m2 mesna was given as a continuous infusion. Forced diuresis was established by giving 6 L of dextrose/saline in 38 hours. Maximally 5 courses were given at 4‐week intervals. VP ‐ carboplatin 400 mg/m2 dissolved in 250 ml dextrose 5% and given as a 30 min IV infusion, and vincristine 2 mg IV bolus on day 1 and 8. Maximally 5 courses were given at 4‐week intervals. CO‐INTERVENTIONS: Patients with a complete response after chemotherapy received prophylactic cranial irradiation 12 x 2.5 Gy
Outcomes	OUTCOMES MEASURED: Tumour response (defined according to standard criteria) Survival Toxicity FOLLOW UP ASSESSMENT POINTS: OUTCOMES INCLUDED IN ANALYSES: Tumour response (defined according to standard criteria) Survival Toxicity
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not reported
Allocation concealment (selection bias)	Unclear risk	Not reported
Blinding (performance bias and detection bias) Participants	Unclear risk	Not reported
Blinding (performance bias and detection bias) Investigators	Unclear risk	Not reported
Blinding (performance bias and detection bias) Survival	Unclear risk	Not reported
Blinding (performance bias and detection bias) Tumour Response	Unclear risk	Not reported
Blinding (performance bias and detection bias) Toxicity	Unclear risk	Not reported
Blinding (performance bias and detection bias) Quality of Life	Unclear risk	N/A
Incomplete outcome data (attrition bias) Survival	High risk	Reasons for withdrawals, drop‐outs and exclusions not reported
Incomplete outcome data (attrition bias) Tumour Response	High risk	Reasons for withdrawals, drop‐outs and exclusions not reported
Incomplete outcome data (attrition bias) Toxicity	High risk	Reasons for withdrawals, drop‐outs and exclusions not reported
Incomplete outcome data (attrition bias) Quality of Life	Unclear risk	N/A
Selective reporting (reporting bias)	Unclear risk	Insufficient information
Other bias	Low risk	Adequate