Greco 2005.

Methods	STUDY DESIGN: Parallel group LOCATION, NUMBER OF CENTRES: 29 affiliate Minnie Pearl Cancer Research Network participating sites DURATION OF STUDY: 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: Patients with previously untreated histologically confirmed SCLC; age > 18 years; Easter Cooperative Oncology Group (ECOG) performance status score of 0 or 1; ANC > 1500/µl; platelet count > 100,000/µl; serum bilirubin <= 1.5 mg/dl, for those without known hepatic metastases, and < 2.5 mg/dl for those with known hepatic metastases; serum creatinine <= 1.5 mg/dl; no previous treatment for small cell lung cancer; no history of prior malignancy within 5 years, with the exception of nonmelanoma skin cancer or cervical carcinoma in situ; and no history of congestive heart failure or myocardial infarction within 3 months. EXCLUSION CRITERIA: Patients with mixed histology lung cancer. N SCREENED: N RANDOMISED: 120 (PCE ‐ 60; PT ‐ 60) N COMPLETED: 120 ASSESS STAGE: Yes (N LIMITED): 0 (N EXTENSIVE): 120 M: PCE ‐ 39; PT ‐ 29 F: PCE ‐ 21; PT ‐ 31 AGE: median age (range): PCE ‐ 60 (42 to 78); PT 62 (38 to 79)
Interventions	TYPE: Chemotherapy REGIMENS: PCE ‐ paclitaxel, carboplatin, etoposide PT ‐ paclitaxel, topotecan Up to 8 cycles After the completion of 4 courses of chemotherapy, patients responding well to treatment and tolerating treatment with no grade 4 toxicity could continue on treatment for a maximum of 8 courses at the discretion of the treating physician PCE ‐ paclitaxel at a dose of 200 mg/m2 IV over 1 hour on day 1; carboplatin dosing was based on the Calvert formula with a target area under the concentration‐time curve of 6 given IV over 1 hour on day 1; etoposide given orally with a total dose of 50 mg, alternating with 100 mg, on a daily basis on days 1 to 10. Repeated every 21 days. PT ‐ paclitaxel was administered at a dose of 175 mg/m2 IV over 1 hour on day 1, and topotecan was given at a dose of 1.5 mg/m2 IV over 1 hour on days 1, 2 and 3. Repeated every 21 days. CO‐INTERVENTIONS: Patients with brain metastases were treated with whole‐brain radiotherapy concurrently with the beginning of chemotherapy. Cytokines were used at the discretion of each investigator; however, they were not used during the first course of therapy. All patients received standard supportive care, including blood and platelet transfusions, antiemetics and antibiotics.
Outcomes	OUTCOMES MEASURED: Primary: tumour response rate; time to progression Secondary: overall survival; toxicity (haematologic and non‐haematologic) FOLLOW UP ASSESSMENT POINTS: Tumour status was assessed after 2 courses of chemotherapy (6 weeks), and thereafter every 2 courses until the completion of treatment (4 to 8 courses). OUTCOMES INCLUDED IN ANALYSES: Tumour response rate Overall survival Toxicity
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	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