Lyss 2002.

Methods	STUDY DESIGN: Parallel study LOCATION, NUMBER OF CENTRES: DURATION OF STUDY: April 1995 to [not reported] 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: Yes GRADE ASSESSMENT QUALITY RATING: High TYPE OF ANALYSIS (AVAILABLE CASE/TREATMENT RECEIVED/ ITT): ITT
Participants	INCLUSION CRITERIA: Extensive stage histologically or cytologically documented small cell carcinoma of the bronchus; included patients with disease that was not considered to be limited stage. Patients were allowed to have evaluable or measurable disease. Patients had to have a CALGB performance status of 0 to 2 (except for patients in Arm 4); have a life expectancy >= 2 months and lack other serious comorbidity. Patients were also required to be at least 2 weeks since major surgery; at least 3 weeks from cranial irradiation; and were not allowed to have received prior pelvic or mediastinal radiotherapy, systemic chemotherapy or to have ongoing need for corticosteroid administration. Each patient had to be aware of the nature of his/her disease and willingly give written consent to participate in the study after being informed of the experimental nature of the therapy, alternatives, potential benefits, side effects, risks and discomfort. EXCLUSION CRITERIA: patients with a prior or concomitant malignancy, other than curatively treated carcinoma in situ of the cervix, basal cell carcinoma of the skin or other primary cancer that had been completely resected more than 5 years ago (without radiotherapy or chemotherapy). Pregnant people and patients who were < 16 years of age were excluded. Patients could not have had serious medical or psychiatric illness that would prevent informed consent or intensive treatment or would limit survival to less than 2 years. N RANDOMISED: 95 ASSESS STAGE: Yes (ED only) (N LIMITED): (N EXTENSIVE): M: 66 F: 24 AGE: mean: Arm 1 ‐ 60.8; Arm 2 ‐ 64.7; Arm 3 ‐ 58.0; Arm 4 ‐ 61.1
Interventions	TYPE: Chemotherapy REGIMENS: Chemotherapy was given every 21 days for 6 cycles in patients with CR, PR or stable disease. Arm 1 ‐ consisted of cisplatin 75 mg/m2 intravenously (IV) on day 1 prior to topotecan 1 mg/m2 IV on days 1 to 5. Arm 2 ‐ cisplatin 75 mg/m2 IV on day 1 prior to paclitaxel 230 mg/m2 IV over 3 hours on day 1. Arm 3 ‐ paclitaxel 230 mg/m2 IV over 3 hours on day 1 prior to topotecan 1 mg/m2 IV on days 1 to 5. Arm 4 ‐ paclitaxel 175 mg/m2 IV over 3 hours on day 1 prior to topotecan 1 mg/m2 IV on days 1 to 5. CO‐INTERVENTIONS: G‐CSF was given for all patients until white blood cell count was 10,000/L after day 15 Dexamethasone for patients who received paclitaxel. Thirty minutes prior to paclitaxel administration they also received cimetidine, diphenhydramine and dexamethasone. For patients who attained a CR from chemotherapy, prophylactic cranial irradiation was allowed at the discretion of the investigator.
Outcomes	OUTCOMES MEASURED: Tumour response Survival Toxicity FOLLOW UP ASSESSMENT POINTS: OUTCOMES INCLUDED IN ANALYSES: Tumour response Survival Toxicity
Notes	Other: Only Arm 1 and Arm 3 were considered for this meta‐analysis Arm 3 was added in October 1997 after early termination of Arms 1 and 3 due to toxicity and after completion of accrual to Arm 2
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