# Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer

Source: https://onco.cc/key-papers/paper-schiller-ecog-1594-four-chemotherapy-regimens-nejm-2002/  
OnCo record `paper-schiller-ecog-1594-four-chemotherapy-regimens-nejm-2002` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

The 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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Tags: lung-evidence
- Journal: New England Journal of Medicine
- Year: 2002
- DOI: 10.1056/NEJMoa011954
- Authors: Schiller JH, Harrington D, Belani CP, et al.
- 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.
- What it means: 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.

## Sources

- N Engl J Med 2002: https://doi.org/10.1056/NEJMoa011954
- PubMed: https://pubmed.ncbi.nlm.nih.gov/11784875/

## Connected records

- roadmaps: [Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs](https://onco.cc/roadmaps/chemotherapy-roadmap/), [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](https://onco.cc/roadmaps/lung-cancer-evidence-roadmap/)
- key papers: [Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials](https://onco.cc/key-papers/paper-nsclc-collaborative-group-chemotherapy-meta-analysis-bmj-1995/), [Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer](https://onco.cc/key-papers/paper-scagliotti-cisplatin-pemetrexed-histology-jco-2008/)
- cancers: [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- drugs: [Carboplatin](https://onco.cc/drugs/carboplatin/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Docetaxel](https://onco.cc/drugs/docetaxel/), [Gemcitabine](https://onco.cc/drugs/gemcitabine/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/)
- companies: [ECOG-ACRIN Cancer Research Group](https://onco.cc/companies/ecog-acrin/)
- terms: [Performance status (ECOG, Karnofsky)](https://onco.cc/terms/performance-status/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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