Hyperfractionated radiation therapy with and without concurrent chemotherapy for advanced non-small cell lung cancer

Locally advanced non-small cell lung cancer (NSCLC) continues to be a frustrating challenge for oncologists. In this group of patients, the overall 5-year survival rates have been 3-6% in prospective randomized trials with radiation therapy (RT) alone.

One hundred sixty-nine patients, 18 years of age or older, with histologically or cytologically proven, advanced, nonresectable NSCLC; a Karnofsky performance status score of 50 or greater; and no previous therapy were treated as follows: treatment arm 1: hyperfractionated radiation therapy (HFX RT) to a total tumor dose of 64.80 Gy (61 patients); treatment arm 2: HFX RT to the same tumor dose with chemotherapy (CT) consisting of 100 mg of carboplatin, days 1 and 2, and 100 mg of etoposide (VP-16), days 1-3, given every week during the RT course (52 patients); and treatment arm 3: HFX RT to the same tumor dose with CT consisting of 200 mg of CBCDA, days 1 and 2, and 100 mg of VP-16, days 1-5, during the first, third, and fifth weeks of the RT course (56 patients). Acute and late toxic effects were scored from 0 (none) to 5 (fatal), according to the Radiation Therapy Oncology Group classification.

The authors observed acute overall Grade 3 toxic effects in 11.5% of patients in treatment arm 1, 13.4% of patients in treatment arm 2, and 16.1% of patients in treatment arm 3. Acute overall Grade 4 toxic effects were observed in 1.6% of patients in treatment arm 1, 3.8% of patients in treatment arm 2, and 10.7% of patients in treatment arm 3. Regarding late toxic effects, we observed late overall Grade 3 toxic effects in 3.3% of patients in treatment arm 1, 11.6% of patients in treatment arm 2, and 15.4% of patients in treatment arm 3. Late overall Grade 4 toxic effects were observed in treatment arms 2 and 3 only: 3.8% in treatment arm 2 and 8.9% in treatment arm 3. No Grade 5 toxic effects were observed during this study.

The acute toxic effects observed during this study in treatment arms 1 and 2 are at least comparable to those previously published in other studies of this type, but a high incidence of acute overall toxic effects was observed in treatment arm 3. Regarding late toxic effects, the authors observed a higher incidence of Grade 3 overall late toxic effects in treatment arm 2 and a high incidence of Grade 4 overall late toxic effects in treatment arm 3. Results of this study show that the addition of CT to HFX RT carries a risk of increased high-grade toxic effects, both acute and late.