Accelerated Fractionation in Inoperable Non-small Cell Lung Cancer. A Phase I/II Study
Background: A prospective, single-treatment-arm, Phase I/II trial was performed to determine the tumor response to an accelerated regimen and assess the feasibility and toxic effects of this approach in patients with inoperable non-small cell lung cancer (NSCLC).
Methods: Thirty-seven previously untreated patients with inoperable NSCLC who had no evidence of metastatic disease entered the study. All patients were able to walk and had disease that was measurable or assessable. Patients with palpable supraclavicular disease and weight loss were also eligible. Radiation therapy consisted of an altered fractionation regimen with a concomitant boost technique. The original lung volume received a dose of 40 Gy in 20 daily fractions to the computerized axial tomography (CT)-defined primary tumor and mediastinal nodes. The boost dose (10 Gy) was administered concomitantly with the last five fractions of the original volume treatments, with an interfraction interval of 6-8 hours. The maximal allowed dose to the cord was 46 Gy.
Results: At a median follow-up of 36 months, complete response was achieved in 29% (9 of 31) of the patients and a partial response in 42% (13 of 31). The overall survival rate at 36 months was 10% (median survival time, 8 months). Survival rates were 25%, 8%, and 0% for the complete responders, partial responders, and nonresponders, respectively. Local failure alone was observed in 35.5% of all patients, local and distant failure in 42%, and distant failure only in 13%. Treatments were well tolerated, and all patients were able to complete the planned regimen. Grade 1 and 2 esophagitis occurred in 65% and 26% of the patients, respectively. The clinical condition of two patients (6%) was compatible with radiation pneumonitis. Moist desquamation of the skin occurred in two patients, but most had either mild (55%) or moderate (19%) skin erythema. Late complications have been limited to radiologically detected lung fibrosis.
Conclusions: The accelerated fractionation schedule used in this trial was well tolerated with shortening of overall treatment time. Local tumor control and overall survival are similar to those resulting from conventional fractionation without an increase in normal tissue effects. These results are encouraging, and additional studies testing higher tumor doses are warranted.