Aggressive Induction and Concurrent Chemoradiation Pays Off in Advanced NSCLC

ORLANDO, Florida—An aggressive strategy of induction and concurrent chemoradiotherapy was feasible and well tolerated in a North Carolina study of advanced non-small-cell lung cancer (NSCLC) patients, reported Mark A. Socinski, MD, director of both the Multidisciplinary Thoracic Oncology Program and the Clinical Trials Program, University of North Carolina, Chapel Hill (ASCO abstract 1266).

"This is a population of patients that is potentially curable, but with standard treatment approaches we only cure 15% to 20%." Dr. Socinski pointed out. "The main problems are local and distant failure, so in this study we incorporated more aggressive systemic therapy with a triplet, and gave more aggressive locoregional therapy in terms of dose escalation with concurrent therapy," he added.

‘Thinking Outside the Box’

The investigators previously demonstrated that induction and concurrent carboplatin (Paraplatin) and paclitaxel with thoracic conformal radiation therapy (TCRT) to a total dose of 74 Gy is tolerable and associated with favorable survival outcomes. Patients receiving this regimen achieved a median survival of 26 months and 1-year survival of 40%. (Cancer 92:1213-1223, 2001). Analysis of the pattern of failure suggested that both locoregional and distant failures were problematic; therefore, a more aggressive regimen was incorporated into a subsequent trial.

Dr. Socinski said this approach reflects the benefit of "thinking outside the box."

"We’ve been stuck with using 60 to 66 Gy, and we know this doesn’t provide locoregional control as well as it should," he said. "Therefore, we think this escalation of dose may be more effective."

The current regimen involved the triplet of carboplatin/irinotecan (CPT-11, Camptosar)/paclitaxel supported by granulocyte colony-stimulating factor (G-CSF, filgrastim [Neupogen]) as induction therapy, followed on day 43 by concurrent carboplatin/paclitaxel and dose-escalated TCRT.

Specifically, the schedule was carboplatin at an AUC of 5, irinotecan at 100 mg/m², paclitaxel at 175 mg/m² (CIP) on days 1 and 22, followed on day 43 by concurrent carboplatin at an AUC of 2 plus paclitaxel at 45 mg/m² weekly (CP) for 7 to 8 weeks and dose-escalated TCRT beginning at 78 Gy and escalating to 82, 86, and 90 Gy.

To date, the study has enrolled 20 patients with stage IIIA (n = 12) and IV (n = 8) NSCLC, and performance status 0 (n = 7) and 1 (n = 13). In the 15 patients evaluable for response to induction CIP, there were 7 partial responses (47%) and 8 patients (53%) with stable disease. There was no early progression of disease. Median gross tumor volume was 79 mL prechemotherapy and 25 mL postchemotherapy.

Five patients have been entered to the 78-Gy cohort, and seven to the 82-Gy cohort. The overall response rate in these 12 patients, assessed 2 to 6 months after all treatments, was 58%, Dr. Socinski reported.

Ongoing Investigation

Survival outcome is premature at this point, but 1-year survival by Kaplan-Meier estimate is 0.77, Dr. Socinski reported. "This is really a phase I experience in the sense that we are looking at dose escalation of radiotherapy as the primary endpoint. We are also interested in the safety and efficacy of the induction triple regimen in this population of patients," he said.

"We have concluded that induction CIP with filgrastim support is active and well tolerated, and that TCRT to 82 Gy with concurrent CP following induction CIP is feasible," he said. "Further dose escalation of TCRT to 86 Gy in this aggressive therapeutic strategy is ongoing."