Sequential Vs. Concurrent Chemotherapy and Radiation Therapy for Inoperable Non-Small Cell Lung Cancer (NSCLC) Analysis of Failures in a Phase III Study (RTOG 9410)

Todd Doyle, MD
OncoLink Assistant Editor
Last Modified: October 23, 2000

Presenter: R. Komaki, MD
Affiliation: University of Texas MD Anderson Cancer Center

Summary:

Since the randomized trial reported by Dillman et al., the standard of care for the treatment of unresectable or inoperable non small cell lung cancer in patients with a good performance status has been sequential chemotherapy followed by thoracic radiation therapy. Recently, this standard of care has been challenged with promising reports of concurrent chemotherapy and radiation therapy for this same patient population. A randomized trial reported by the West Japan Lung Cancer Study Group reported a statistically significant improvement in median survival in favor of concurrent over sequential chemoradiotherapy.

Despite modest improvements in survival with concurrent treatment, there remains an overwhelming percentage of patients who suffer local failure. The three arm trial reporte here, RTOG 94-10, was designed to compare sequential versus concurrent chemotherapy with radiation therapy as well as to elucidate any possible benefit of hyperfractionation on local control and survival.

Methods:

Six hundred and ten patients with stage II-III inoperable or unresectable NSC lung cancer were randomized to one of three arms: 1. Sequential chemotherapy (cisplatin/vinblastine) on days 1,29 for five cycles followed by thoracic RT (60 Gy in 6 weeks) or 2. Concurrent chemotherapy (cisplatin/vinblastine) on days 1,29 for five cylces begun on day 1 with RT (60 Gy in 6 weeks) or 3. Concurrent chemotherapy (cisplatin/etoposide) weeks 1,2,5,6 begun on day 1 with RT (69.6 Gy in 1.2 Gy fractions in 6 weeks).
Patients were required to have a KPS greater than or equal to 70% and less than or equal to 5% weight loss.

Results:

The median survival times for both the concurrent once daily arm and the concurrent twice daily arm were statistically significantly better than the sequential arm (17 months, 16 months, and 14.6 months, respectively).
The time to infield progression was significantly longer for the concurrent bid arm overall and when compared to the sequential arm.
There was no statistically significant difference in the overall survival between the concurrent once daily and concurrent twice daily arms.
Significantly higher rates of non-hematologic toxicity was seen in the concurrent bid arm (63%) than the concurrent qd arm (50%)or the sequential arm (31%).
There was no statistically significant difference in the rate of late non-hematologic toxicity.
On subgroup analysis, there was a significant difference in time to infield failure favoring concurrent bid radiation over concurrent qd radiation for squamous cell histology only.

Author's Conclusions:

Concurrent platinum based chemotherapy and daily thoracic radiation therapy show promising results.
Concurrent chemotherapy and bid radiation therapy has significantly less in field failures compared to the sequential group.
Concurrent chemotherapy and bid radiation therapy prolongs time to in field failure in the squamous cell histology patients.

Clinical/Scientific Implications:

This trial clearly defines the standard of care in inoperable and unresectable stage II-III NSC lung cancer as platinum based chemotherapy concurrent with thoracic radiation therapy.
The role of hyperfractionation concurrent with chemotherapy has yet to be fully demonstrated.
New and innovative approaches to improving local thoracic tumor control, and hopefully survival, are needed.