Comparison of Four Chemotherapy Regimens for Advanced Non–Small-Cell Lung Cancer
- Study type
- Clinical trial
- Study name
- ECOG 1594
- Design
- Randomised multi-arm study (4 chemotherapy regimens) by the Eastern Cooperative Oncology Group
- Sample size
- 1207 patients randomised; 1155 eligible patients
- Source
- N Engl J Med · 2002
In plain words
In this large study, four chemotherapy drug combinations for advanced non-small cell lung cancer were compared. The results showed that the response to treatment and how long patients lived did not differ in any important way between the four approaches. The differences were mainly in the type of side effects; for example, one of the regimens caused more kidney damage. Patients who were less able to carry out their daily activities also lived for a shorter time.
Key results
Treatment arms and regimens
Paclitaxel 135 mg/m² as a 24-hour IV infusion + cisplatin 75 mg/m² IV, every 21 days.
Cisplatin 100 mg/m² IV + gemcitabine 1000 mg/m² (1 g/m²) IV on days 1, 8 and 15, every 28 days.
Cisplatin 75 mg/m² + docetaxel 75 mg/m² IV, every 21 days.
Paclitaxel 225 mg/m² as a 3-hour IV infusion + carboplatin AUC 6 IV. The cycle interval for this arm is not stated in the source reviewed.
Source of the regimen details: Abstract of the report of this trial in patients with performance status 2 (Sweeney et al., Cancer 2001; PMID 11745199), which states the doses and schedules of the four E1594 arms. The full text of the NEJM paper was not available and the trial is not registered on ClinicalTrials.gov; the number of cycles, the day of cisplatin administration in the gemcitabine arm and the cycle interval of the carboplatin–paclitaxel arm are not given in this source.
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients with advanced non-small cell lung cancer (1207 patients randomised; 1155 eligible patients). Randomisation was stratified by ECOG performance status. Enrolment of patients with performance status 2 was stopped because of perceived unacceptable toxicity (68 patients with performance status 2 had been enrolled before the closure). Other eligibility criteria are not stated in the sources reviewed.
Endpoints
The aim of the study was to determine whether any of the three experimental regimens was superior to cisplatin and paclitaxel. According to the abstract, response rate, survival, time to progression and toxicity were assessed; the exact primary endpoint is not stated in the abstract.
Safety and side effects
Cisplatin and gemcitabine was associated with grade 3, 4 or 5 renal toxicity in 9% of patients, compared with 3% in the cisplatin and paclitaxel group. In the performance status 2 subgroup (64 evaluable patients; Sweeney et al. 2001): grade 3–4 haematological toxicity occurred in more than 50% of patients in each treatment group; grade 3–4 non-haematological toxicity was significantly lower in the paclitaxel and carboplatin arm (P=0.0032); there were 5 deaths on treatment (7.35%), 2 of which were attributed to treatment; median survival in this subgroup was 4.1 months. Other adverse event rates are not reported in the sources reviewed.
Clinical significance and place in guidelines
According to the abstract, none of the three experimental regimens was significantly superior to cisplatin and paclitaxel in response or survival. In practice, therefore, the choice of regimen can be based on the adverse event profile (e.g. more renal toxicity with cisplatin and gemcitabine) and the patient's condition. The current status of these regimens in treatment guidelines and the place of targeted therapies and immunotherapy should be checked in up-to-date guidelines.
Limitations
The abstract compares only chemotherapy regimens from past decades and does not state doses or schedules; the doses on this card come from a separate report of the same trial (Sweeney et al., Cancer 2001), and the number of cycles is not stated in the available sources. Numerical values for time to progression are not reported in the abstract. The main message of the study is the absence of a significant advantage in survival and response rate, and it does not cover results with newer treatments.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.