{"entity":{"id":"paper-schiller-ecog-1594-four-chemotherapy-regimens-nejm-2002","kind":"paper","name":"Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer","aka":[],"tldr":"1,207 patients were randomised between four platinum doublets. All four gave the same result: about one in five responded and median survival was just under eight months. Chemotherapy had reached a ceiling.","summary":"The Eastern Cooperative Oncology Group's E1594 trial, reported by Schiller, Harrington, Belani, Langer, Sandler, Krook, Zhu and Johnson. A reference regimen of cisplatin and paclitaxel was compared against cisplatin and gemcitabine, cisplatin and docetaxel, and carboplatin and paclitaxel in 1,207 patients with advanced non-small-cell lung cancer, of whom 1,155 were eligible.\n\nThe trial is remembered for a negative result that mattered: no regimen was better than any other, so the choice between them became a matter of toxicity, convenience and cost. It fixed the plateau that targeted therapy and immunotherapy were later measured against, and it is the reason a median survival of about eight months is the reference point for advanced lung cancer in 2002.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2002","url":"https://doi.org/10.1056/NEJMoa011954"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/11784875/"}],"tags":["lung-evidence"],"related":["chemotherapy-roadmap","paper-nsclc-collaborative-group-chemotherapy-meta-analysis-bmj-1995","paper-scagliotti-cisplatin-pemetrexed-histology-jco-2008"],"cancers":["lung-cancer","nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["cisplatin","carboplatin","paclitaxel","docetaxel","gemcitabine"],"companies":["ecog-acrin"],"institutions":[],"pathways":[],"terms":["performance-status"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2002,"doi":"10.1056/NEJMoa011954","pmid":"11784875","authors":"Schiller JH, Harrington D, Belani CP, et al.","paperType":"rct","findings":["Response rate 19 percent across all 1,155 eligible patients; median survival 7.9 months (95 percent confidence interval 7.3 to 8.5).","One-year survival 33 percent (30 to 36) and two-year survival 11 percent (8 to 12).","Neither response rate nor survival differed significantly between the reference regimen and any of the three experimental regimens.","Cisplatin and gemcitabine gave a significantly longer time to progression than cisplatin and paclitaxel but caused more grade 3, 4 or 5 renal toxicity (9 percent against 3 percent).","Patients with a performance status of 2 had significantly lower survival than those with performance status 0 or 1."],"whatItMeans":"The ceiling of undirected cytotoxic chemotherapy, measured precisely. Everything that came afterwards, from histology-directed pemetrexed to EGFR inhibitors to checkpoint blockade, is an attempt to break a plateau this trial demonstrated could not be broken by changing the drugs.","caveats":["Four regimens, not a test of whether chemotherapy helps at all; that question was settled by the 1995 meta-analysis.","Molecular subgroups were unknown in 2002, so a trial of unselected patients averaged over populations now treated completely differently.","Performance status 2 patients did badly and remain under-represented in lung cancer trials."],"changedPractice":true,"participants":1207},"route":"/key-papers/paper-schiller-ecog-1594-four-chemotherapy-regimens-nejm-2002/","neighbours":{"roadmap":[{"id":"chemotherapy-roadmap","kind":"roadmap","name":"Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs","route":"/roadmaps/chemotherapy-roadmap/"},{"id":"lung-cancer-evidence-roadmap","kind":"roadmap","name":"Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch","route":"/roadmaps/lung-cancer-evidence-roadmap/"}],"paper":[{"id":"paper-nsclc-collaborative-group-chemotherapy-meta-analysis-bmj-1995","kind":"paper","name":"Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials","route":"/key-papers/paper-nsclc-collaborative-group-chemotherapy-meta-analysis-bmj-1995/"},{"id":"paper-scagliotti-cisplatin-pemetrexed-histology-jco-2008","kind":"paper","name":"Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer","route":"/key-papers/paper-scagliotti-cisplatin-pemetrexed-histology-jco-2008/"}],"cancer":[{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"drug":[{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"docetaxel","kind":"drug","name":"Docetaxel","route":"/drugs/docetaxel/"},{"id":"gemcitabine","kind":"drug","name":"Gemcitabine","route":"/drugs/gemcitabine/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"}],"company":[{"id":"ecog-acrin","kind":"company","name":"ECOG-ACRIN Cancer Research Group","route":"/companies/ecog-acrin/"}],"term":[{"id":"performance-status","kind":"term","name":"Performance status (ECOG, Karnofsky)","route":"/terms/performance-status/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}