de Jong 2007.

Methods	STUDY DESIGN: Parallel group LOCATION, NUMBER OF CENTRES: Not described DURATION OF STUDY: Feb 1999 – Feb 2005 CONCEALMENT OF ALLOCATION: B DESCRIBED AS RANDOMISED: Yes DESCRIBED AS DOUBLE BLIND: Not described METHOD OF RANDOMISATION WELL DESCRIBED/APPROPRIATE: Yes METHOD OF BLINDING WELL DESCRIBED/APPROPRIATE: N/A DESCRIPTION OF WITHDRAWALS/DROPOUTS: Appropriate GRADE ASSESSMENT QUALITY RATING: High TYPE OF ANALYSIS (AVAILABLE CASE/TREATMENT RECEIVED/ ITT): ITT COMPLIANCE: CONFOUNDERS:
Participants	ELIGIBILITY INCLUSION CRITERIA: Patients were included if they met all the following criteria: age over 18 years, histologically or cytologically proven ED SCLC with measurable or evaluable lesions, no prior chemotherapy or radiotherapy except for symptomatic brain metastases, Eastern Cooperative Oncology Group (ECOG) performance score 0–2, adequate haematological, renal and hepatic functions (absolute neutrophil count (ANC) P2.0 x 10^9/L, platelet count P100 · 109/L, bilirubin 61.25 · upper normal limit, creatinine clearance according to Cockroft formula P60 ml/min). EXCLUSION CRITERIA: N SCREENED: Unknown N RANDOMISED: 203 N COMPLETED: 203 (CDE ‐ 102; CP – 101) ASSESS STAGE: Yes (N LIMITED): N/A (N EXTENSIVE): 203 M: 118 (CDE – 52; CP – 63) F: 85 (CDE – 47; CP – 38) MEDIAN AGE: CDE – 61.7; CP – 62.7 BASELINE DETAILS: History, physical examination, ECOG performance status, complete blood cell count (CBC), electrolytes, liver enzymes, serum creatinine and electrocardiography (ECG)
Interventions	TYPE: Chemotherapy REGIMENS, DOSE, DELIVERY: CDE ‐ Cyclophosphamide (1000 mg/m2 i.v) on day 1, doxorubicin (45 mg/m2 i.v) on day 1, and etoposide (100 mg/m2 i.v) on days 1, 2, and 3. Carboplatin (AUC 7 using the Calvert formula, i.v) followed by paclitaxel (175 mg/m2 i.v) as a 3‐hour infusion both on day 1 CYCLES: Maximum of 5 cycles every 3 weeks CO‐INTERVENTIONS PERMITTED: Nil CO‐INTERVENTIONS: Nil
Outcomes	OUTCOMES MEASURED: Primary – Progression free survival, Secondary – Overall survival, tumour response rates, toxicities FOLLOW‐UP ASSESSMENT POINTS: On day 14 of each cycle and on clinical indications, a CBC was performed in a similar way in both arms. Tumour evaluations were performed with a computed tomography (CT) scan of the chest and repeated after two cycles and at the end of treatment. Tumour response was defined according to the WHO criteria. Follow‐up after treatment was every 4–6 weeks with a CBC, liver enzymes, chest X‐ray, or additional tests if clinically indicated. Toxicity was scored before each cycle according to the National Cancer Institute Common Toxicity Criteria (CTC), version 2.0. OUTCOMES INCLUDED IN ANALYSES: Progression‐free survival Overall survival Tumour response rates Toxicities SUB‐GROUPS INDENTIFIED: Nil
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Described and appropriate
Allocation concealment (selection bias)	Low risk	Described and appropriate
Blinding (performance bias and detection bias) Participants	Unclear risk	Not described
Blinding (performance bias and detection bias) Investigators	Unclear risk	Not described
Blinding (performance bias and detection bias) Survival	Unclear risk	Not described
Blinding (performance bias and detection bias) Tumour Response	Unclear risk	Not described
Blinding (performance bias and detection bias) Toxicity	Unclear risk	Not described
Blinding (performance bias and detection bias) Quality of Life	Unclear risk	Not described
Incomplete outcome data (attrition bias) Survival	Low risk	All randomised patients accounted for; withdrawals and dropouts adequately described
Incomplete outcome data (attrition bias) Tumour Response	Low risk	All randomised patients accounted for; withdrawals and dropouts adequately described
Incomplete outcome data (attrition bias) Toxicity	Low risk	All randomised patients accounted for; withdrawals and dropouts adequately described
Incomplete outcome data (attrition bias) Quality of Life	Unclear risk	Not assessed
Selective reporting (reporting bias)	Low risk	Adequate