Combined Chemotherapy and Radiotherapy Recommended for Advanced Non-Small-Cell Lung Cancer

Patients with advanced non-small-cell lung cancer (NSCLC) whoare 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 RobertO. Dillman, md, and colleagues at the Hoag Cancer Center, NewportBeach, California. In the study report appearing in the September4th issue of the Journal of the National Cancer Institute, theauthors recommend that cisplatin (Platinol)-based chemotherapyfollowed by radiation therapy be considered the current standardtreatment for advanced (stage III) disease.

This study by the Cancer and Leukemia Group B (CALGB) involved155 patients who had stage III NSCLC, 77 of whom were randomlyassigned to receive radiation therapy alone and 78 of whom receivedchemotherapy followed by radiation therapy. The patients werefollowed for at least 7 years. According to the researchers, althoughprevious studies have suggested that chemotherapy and radiationtherapy 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 receiveda total of 6,000 cGy of radiation in 30 sessions over a 6- to7-week period. In 20 of these sessions, 200-cGy doses were deliveredto the original tumor volume, and, in 10 sessions, 200 cGy wasdelivered to include the volume surrounding the tumor.

The sequential-therapy group received five doses of vinblastineand two doses of cisplatin over a 30-day period, followed 2 to3 weeks later by the radiation treatment described above. Tumorregression was determined after the completion of chemotherapy,1 month after radiation treatment ended for both groups, and thereafterat 2-month intervals,

Median survival was 13.7 months for the combination-therapy groupand 9.6 months for the radiation therapy-only group. Survivalrates after 1 year were 54% for the patients receiving combinationtherapy and 40% for those receiving radiation therapy alone. After2 years, survival rates were 26% for the combination-therapy groupand 13% for those receiving radiation therapy alone. Five yearsafter treatment started, survival was 2.8 times greater for thecombination-therapy patients than for the radiation therapy-onlypatients (17% vs 6%). With 6 to 7 years of follow-up, survivalrates were 13% among patients who received combination therapyand 6% among patients who received radiation therapy alone. Accordingto the authors, if the survival advantage found in this studycould be extended to all patients with stage III NSCLC, as manyas an additional 5,100 patients per year might survive 5 years

The researchers note that some physicians question the use ofchemotherapy in the treatment of NSCLC because of concerns aboutside effects and risk-benefit issues. Therefore, they say, itis worth noting that the survival advantage demonstrated in thisstudy was achieved without clinically important increases in toxiceffects. There have been major advances in supportive care ofpatients who receive chemotherapy since the treatment phase ofthis study was completed, they add.

Despite the improved survival resulting from combined chemotherapyand radiotherapy, the fact that 80% to 85% of the patients inthis study died of their cancers within 5 years means that bettertreatments are needed, the researchers point out. New agents,such as ifosfamide (Ifex) and paclitaxel (Taxol), and new approaches,such as the use of chemotherapy or chemotherapy and radiationtherapy 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 UniversityMedical School, Nashville, Tennessee, suggests that all partiesneed to exert caution in the application of these latest researchfindings. He points out that the results reported by Dillman etal were obtained in patients having a good performance status(Eastern Cooperative Oncology Group 0 or 1) , little or no weightloss, no supraclavicular lymph node involvement, and no pleuraleffusion. Furthermore, he says, no details are provided abouttreatment failure and causes of death, and, lacking such data,it is reasonable to assume that treatment failure included bothlocal progression and distant metastases. However, Johnson says,a European study in which survival was improved through controlof local progression alone challenges the premise that controlof distant metastases is a must for improved survival. He concludesthat use of combined chemotherapy and radiotherapy is appropriatefor selected NSCLC patients, but making an individual treatmentrecommendation comes down to sound clinical judgment.