Roth 1992.

Methods	STUDY DESIGN: Parallel study LOCATION, NUMBER OF CENTRES: United States of America; multicentric DURATION OF STUDY: February 1985 to April 1989 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: Age >= 18 years; histologic or cytologic confirmation of SCLC of the lung; no prior chemotherapy or radiotherapy; patients had extensive disease (ED) which is defined as disease spread beyond the primary site, mediastinum and ipsilateral supraclavicular lymph nodes; patients with brain metastases were eligible; adequate bone marrow reserve was required (total leukocyte count >= 4000 / µL and platelet count >= 100 000/ µL) although patients with documented bone marrow involvement were eligible if their leukocyte and platelet count were greater than 3000 /µL and greater than 50 000 /µL, respectively; adequate hepatic function, defined as serum total bilirubin level less than 2.9 mg/dL; adequate renal function with a serum creatinine level <= 1.8 mg/dL for men or <= 1.5 mg/dL for women; a Zubrod performance status of 0 to 3 was required; all patients gave written consent before entry. EXCLUSION CRITERIA: Patients with malignant pleural effusions as their only site of metastatic disease; patients with previous or concomitant malignancy other than adequately treated squamous cell or basal cell carcinoma or in situ carcinoma of the uterine cervix; patients with clinical congestive cardiac failure, cardiac arrhythmias requiring medical therapy or who had myocardial infarction within 3 months of diagnosis. N RANDOMISED: 437 (EP ‐ 148; CAV ‐ 146; CAV/EP ‐ 143) ASSESS STAGE: Yes (ED only) (N LIMITED): (N EXTENSIVE): 437 M: 370 F: 107 AGE: median EP ‐ 62.2; CAV ‐ 61.7; CAV/EP ‐ 62.6
Interventions	TYPE: Chemotherapy REGIMENS: Regimen A: EP ‐ cisplatin 20 mg/m2/d IV for 5 days in combination with etoposide 80 mg/m2/d IV for 5 days, repeated every 3 weeks for 4 cycles (12 weeks) Regimen B: CAV ‐ cyclophosphamide 1000 mg/m2, doxorubicin 40 mg/m2 and vincristine 1 mg/m2 (maximum 2.0 mg), all given IV on day 1 and repeated every 3 weeks for 6 cycles (18 weeks) CAV/EP ‐ CAV in the same dosages as in regimen B was given on day 1 and EP given in the same dosages as in regimen A on days 22 to 26, with cycles repeated every 6 weeks for 3 cycles (18 weeks) CO‐INTERVENTIONS: Patients with brain metastases were required to have concomitant whole brain radiotherapy and chemotherapy at the initiation of the study
Outcomes	OUTCOMES MEASURED: Tumour response Survival Toxicity FOLLOW UP ASSESSMENT POINTS: OUTCOMES INCLUDED IN ANALYSES: Tumour response Survival Toxicity
Notes	In the cisplatin containing arms, sufficient hydration to ensure a urinary output of at least 100 cc/h before and for 4 hours after the infusion of cisplatin was required
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)	Low risk	Adequate
Other bias	Low risk	Adequate