White 2001.

Methods	STUDY DESIGN: Parallel group LOCATION, NUMBER OF CENTRES: DURATION OF STUDY: June 1996 to January 1999 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: Adequate GRADE ASSESSMENT QUALITY RATING: High TYPE OF ANALYSIS (AVAILABLE CASE/TREATMENT RECEIVED/ ITT): ITT
Participants	ELIGIBILITY INCLUSION CRITERIA: Patients with histologically or cytologically proven SCLC were eligible for inclusion in the study. They were required to have either a Karnofsky Performance status <= 50 and/or at least 2 of the following adverse prognostic indicators: Karnofsky Performance status < 60; extensive disease; and elevated alkaline phosphatase, lactic dehydrogenase, or low sodium. Patients had received no previous chemotherapy, surgery, or radiotherapy for SCLC, and no prior malignancy was permitted except basal cell carcinoma of the skin or in situ carcinoma of the cervix. A creatinine clearance of at least 30 mL per minute was required, and patients with liver derangement were only eligible if their plasma bilirubin was < 35 mol/L. EXCLUSION CRITERIA: N SCREENED: N RANDOMISED: 119 (CAV ‐ 59; Carboplatin ‐ 60) N COMPLETED: ASSESS STAGE: Yes (N LIMITED): (CAV ‐ 17; Carbo ‐ 21) (N EXTENSIVE): (CAV ‐ 42; Carbo ‐ 39) M: (CAV ‐ 34; Carbo ‐ 29) F: (CAV ‐ 25; Carbo ‐ 31) MEAN AGE: CAV ‐ median 70 (46 to 85); Carbo 70 (54 to 76)
Interventions	REGIMENS: Control arm ‐ in the control arm, CAV was administered on day 1 of a 3‐week cycle for 4 cycles. This consisted of cyclophosphamide 750 mg/m2 IV, vincristine 1.3 mg/m2 IV (to a maximum of 2 mg), and doxorubicin 40 mg/m2 IV, all given as a bolus on day 1. Experimental arm ‐ patients who were allocated to the experimental arm received 4 courses of single‐agent carboplatin IV infused over 1 hour and administered at 4‐week intervals. The dosage was derived from the formula of Calvert giving an AUC of 7. Dose reductions were not performed. Chemotherapy was delayed if there was evidence of sepsis or persisting myelosuppression (white blood cells < 3000/mm3, neutrophils < 1500/mm3, and platelets < 100,000/mm3) at the time of scheduled retreatment. Control arm ‐ In the event of significant peripheral neuropathy, vincristine was omitted. CO‐INTERVENTIONS: Patients who had limited disease and an objective response to treatment could be considered for consolidation thoracic and prophylactic cranial irradiation. Erythropoietin and growth factors were permitted at the individual physician's discretion.
Outcomes	OUTCOMES MEASURED: Primary: toxicity Secondary: objective response rate; survival; quality of life FOLLOW UP ASSESSMENT POINTS: OUTCOMES INCLUDED IN ANALYSES: Toxicity Objective response rate Survival Quality of life
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	Low risk	Reasons for withdrawals, drop‐outs and exclusions reported
Incomplete outcome data (attrition bias) Tumour Response	Low risk	Reasons for withdrawals, drop‐outs and exclusions reported
Incomplete outcome data (attrition bias) Toxicity	Low risk	Reasons for withdrawals, drop‐outs and exclusions 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