Patients with advanced non-small-cell lung cancer (NSCLC) who are treated with chemotherapy and radiation therapy live longer, on average, than patients treated with radiation therapy alone, according to results of a long-term follow-up study by Robert O. Dillman, md, and colleagues at the Hoag Cancer Center, Newport Beach, California. In the study report appearing in the September 4th issue of the Journal of the National Cancer Institute, the authors recommend that cisplatin(Drug information on cisplatin) (Platinol)-based chemotherapy followed by radiation therapy be considered the current standard treatment for advanced (stage III) disease.
This study by the Cancer and Leukemia Group B (CALGB) involved 155 patients who had stage III NSCLC, 77 of whom were randomly assigned to receive radiation therapy alone and 78 of whom received chemotherapy followed by radiation therapy. The patients were followed for at least 7 years. According to the researchers, although previous studies have suggested that chemotherapy and radiation therapy confer a survival benefit in patients with stage III NSCLC, follow-up in these studies has been limited to 2 to 3 years.
In the CALGB study, the radiation therapy-only group received a total of 6,000 cGy of radiation in 30 sessions over a 6- to 7-week period. In 20 of these sessions, 200-cGy doses were delivered to the original tumor volume, and, in 10 sessions, 200 cGy was delivered to include the volume surrounding the tumor.
The sequential-therapy group received five doses of vinblastine(Drug information on vinblastine) and two doses of cisplatin over a 30-day period, followed 2 to 3 weeks later by the radiation treatment described above. Tumor regression was determined after the completion of chemotherapy, 1 month after radiation treatment ended for both groups, and thereafter at 2-month intervals,
Median survival was 13.7 months for the combination-therapy group and 9.6 months for the radiation therapy-only group. Survival rates after 1 year were 54% for the patients receiving combination therapy and 40% for those receiving radiation therapy alone. After 2 years, survival rates were 26% for the combination-therapy group and 13% for those receiving radiation therapy alone. Five years after treatment started, survival was 2.8 times greater for the combination-therapy patients than for the radiation therapy-only patients (17% vs 6%). With 6 to 7 years of follow-up, survival rates were 13% among patients who received combination therapy and 6% among patients who received radiation therapy alone. According to the authors, if the survival advantage found in this study could be extended to all patients with stage III NSCLC, as many as an additional 5,100 patients per year might survive 5 years
The researchers note that some physicians question the use of chemotherapy in the treatment of NSCLC because of concerns about side effects and risk-benefit issues. Therefore, they say, it is worth noting that the survival advantage demonstrated in this study was achieved without clinically important increases in toxic effects. There have been major advances in supportive care of patients who receive chemotherapy since the treatment phase of this study was completed, they add.
Despite the improved survival resulting from combined chemotherapy and radiotherapy, the fact that 80% to 85% of the patients in this study died of their cancers within 5 years means that better treatments are needed, the researchers point out. New agents, such as ifosfamide(Drug information on ifosfamide) (Ifex) and paclitaxel(Drug information on paclitaxel) (Taxol), and new approaches, such as the use of chemotherapy or chemotherapy and radiation therapy before surgery, need to be evaluated in rigorous, prospective, randomized trials.
Results Should Be Applied Cautiously
In a related editorial, David H. Johnson, md, of Vanderbilt University Medical School, Nashville, Tennessee, suggests that all parties need to exert caution in the application of these latest research findings. He points out that the results reported by Dillman et al were obtained in patients having a good performance status (Eastern Cooperative Oncology Group 0 or 1) , little or no weight loss, no supraclavicular lymph node involvement, and no pleural effusion. Furthermore, he says, no details are provided about treatment failure and causes of death, and, lacking such data, it is reasonable to assume that treatment failure included both local progression and distant metastases. However, Johnson says, a European study in which survival was improved through control of local progression alone challenges the premise that control of distant metastases is a must for improved survival. He concludes that use of combined chemotherapy and radiotherapy is appropriate for selected NSCLC patients, but making an individual treatment recommendation comes down to sound clinical judgment.