Fukuoka 1991.
| Methods | STUDY DESIGN: Parallel group
LOCATION, NUMBER OF CENTRES:
DURATION OF STUDY: April 1985 to May 1988
CONCEALMENT OF ALLOCATION: D
DESCRIBED AS RANDOMISED: Yes
DESCRIBED AS DOUBLE BLIND: No
METHOD OF RANDOMISATION WELL‐DESCRIBED/APPROPRIATE: Adequate
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 |
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| Participants | INCLUSION CRITERIA: Histologically or cytologically proven SCLC; no prior therapy; signs of measurable or evaluable disease; a performance status of 0 to 3 on the Eastern Cooperative Oncology Group (ECOG) scale; age less than 75 years; adequate bone marrow reserve (leukocyte count >= 4000/mm3 and platelet count >= 100,000/mm3); adequate liver function (bilirubin <= 1.5 mg/dL and alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase no greater than twice the upper limit of normal); adequate renal function (serum creatinine <= 1.5 mg/dL and blood urea nitrogen <= 25 mg/dL) and informed consent. EXCLUSION CRITERIA: Ineligible if patients had another active malignant disease, a history of myocardial infarction within the previous 3 months or other cardiac disease requiring medical treatment. N SCREENED: 300 (288 eligible) N RANDOMISED: 288 (CAV ‐ 97; PE ‐ 97; CAV/PE ‐ 94) N COMPLETED: 279 ASSESS STAGE: Yes (N LIMITED): CAV ‐ 49; PE ‐ 47; CAV/PE ‐ 50 (N EXTENSIVE): CAV ‐ 48; PE ‐ 50; CAV/PE ‐ 44 M: CAV ‐ 81; PE ‐ 78; CAV/PE ‐ 76 F: CAV ‐ 16; PE ‐ 19; CAV/PE ‐ 18 AGE: median: CAV ‐ 63; PE ‐ 64; CAV/PE ‐ 64 (range: CAV ‐ 40 to 74; PE ‐ 37to 74; CAV/PE ‐ 31 to 74) |
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| Interventions | TYPE: Chemotherapy
REGIMENS:
CAV ‐ cyclophosphamide at a dose of 800 mg/m2 given intravenously (IV) on day 1, doxorubicin at 50 mg/m2 IV on day 1 and vincristine at 1.4 mg/m2 (maximum 2.0 mg) IV on day 1.
PE ‐ cisplatin at 80 mg/m2 IV on day 1 and etoposide at 100 mg/m2 IV on days 1, 3 and 5.
(Cisplastin was given with adequate prehydration, posthydration, diuretics and antiemetic agents) CAV/PE ‐ CAV alternating with PE Treatments were repeated every 3 to 4 weeks CO‐INTERVENTIONS: All patients with limited disease received thoracic irradiation after restaging. Thoracic irradiation consisted of 200‐cGy fractions given daily 5 days per week for 4 to 5 weeks. |
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| Outcomes | OUTCOMES MEASURED:
Tumour response (classified according to World Health Organization criteria)
Survival
Toxicity FOLLOW UP ASSESSMENT POINTS: OUTCOMES INCLUDED IN ANALYSES: Tumour response (classified according to World Health Organization criteria) Survival Toxicity |
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| Notes | Other: There were 3 cancellations due to patient refusal before therapy started; 9 patients were considered ineligible: 4 had histologies other than SCLC, 3 were 75 years of age or older, one had congestive heart failure and one had a simultaneous squamous cell carcinoma of the lung. If patients on the CAV arm or PE arm did not respond after 2 cycles of chemotherapy, they were crossed over to the other regimen (restaging). Restaging was carried out at the completion of 4 cycles of chemotherapy to evaluate the response. Cisplastin was discontinued if renal failure occurred. |
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| 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 |