Jones 1993.

Methods	STUDY DESIGN: Parallel study LOCATION, NUMBER OF CENTRES: DURATION OF STUDY: August 1987 to April 1990 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: Previously untreated patients; histologically or cytologically confirmed SCLC; World Health Organization performance status EXCLUSION CRITERIA: N RANDOMISED: 104 (CVM ‐ 54; ACE ‐ 50) ASSESS STAGE: Yes (N LIMITED): 32 (CVM ‐ 17; ACE ‐ 15) (N EXTENSIVE): 72 (CVM ‐ 37; ACE ‐ 35) M: 61 F: 43 AGE: median: CVM ‐ 67; ACE ‐ 64 (range: CVM ‐ 33 to 79; ACE ‐ 47 to 75)
Interventions	TYPE: Chemotherapy REGIMENS: CVM ‐ carboplatin 300 mg/m2 in 500 ml (Dextrose 5% in Water solution) delivered intravenously (IV) over 60 minutes, on day 1, vinblastine 6 to 10 mg/m2 IV on day 1, and methotrexate 30 to 50 mg/m2 IV on day 1. The course was repeated every 28 days. Leucovorin was administered orally 24 hours after methotrexate to reverse the latter agent's toxic effects (15 mg every 6 hours × 6 doses) ACE ‐ doxorubicin 40 mg/m2 IV on day 1, cyclophosphamide 600 mg/m2 IV on day 1 and etoposide 100 mg/m2 days 1 to 3 (outpatient treatment: 200 mg/m2 orally. days 2 and 3). The course was repeated every 21 days CO‐INTERVENTIONS: Some limited disease (LD) patients who did not respond to chemotherapy were given thoracic radiotherapy Prophylactic cranial radiotherapy was also given to some patients
Outcomes	OUTCOMES MEASURED: Tumour response Toxicity FOLLOW UP ASSESSMENT POINTS: OUTCOMES INCLUDED IN ANALYSES: Tumour response Toxicity
Notes	To prevent vomiting dexamethasone and metoclopramide (8 and 20 mg respectively) were administered IV prior to the first chemotherapy course and orally after chemotherapy (4 and 10 to 20 mg respectively, every 4 hours over 48 hours). Thereafter the doses of the antiemetics were modified as needed. If platelet and leukocyte counts had not returned to at least 3 × 109/L and 100 × 109/L, respectively, by the time of the next treatment cycle, an additional week of no treatment was added before the cycle began to allow blood count recovery. Doses of all chemotherapy agents were reduced by 25% for the duration of the study if 2 treatment cycle delays occurred. During part of the selection period, patients with limited disease and a good performance status (grade 1 to 2) had the option of undergoing intensive therapy with other protocols.
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