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Mediastinal Lymph Node Clearance After Docetaxel-Cisplatin Neoadjuvant Chemotherapy Is Prognostic of Survival in Patients With Stage IIIA pN2 Non–Small-Cell Lung Cancer: A Multicenter Phase II Trial

Daniel C. Betticher, Shu-Fang Hsu Schmitz, Martin Tötsch, Eva Hansen, Christine Joss, Christian von Briel, Ralph A. Schmid, Miklos Pless, James Habicht, Arnaud D. Roth, Anastase Spiliopoulos, Rolf Stahel, Walter Weder, Roger Stupp, Fritz Egli, Markus Furrer, Hanspeter Honegger, Martin Wernli, Thomas Cerny, Hans-Beat Ris

From the Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland.

Address reprint requests to Daniel Betticher, MD, Institute of Medical Oncology, University of Bern, 3010 Bern, Switzerland; email: daniel.betticher{at}insel.ch.

Purpose: A multicenter, phase II trial investigated the efficacy and toxicity of neoadjuvant docetaxel-cisplatin in locally advanced non–small-cell lung cancer (NSCLC) and examined prognostic factors for patients not benefiting from surgery.

Patients and Methods: Ninety patients with previously untreated, potentially operable stage IIIA (mediastinoscopically pN2) NSCLC received three cycles of docetaxel 85 mg/m² day 1 plus cisplatin 40 mg/m² days 1 and 2, with subsequent surgical resection.

Results: Administered dose-intensities were docetaxel 85 mg/m²/3 weeks (range, 53 to 96) and cisplatin 95 mg/m²/3 weeks (range, 0 to 104). The 265 cycles were well tolerated, and the overall response rate was 66% (95% confidence interval [CI], 55% to 75%). Seventy-five patients underwent tumor resection with positive resection margin and involvement of the uppermost mediastinal lymph node in 16% and 35% of patients, respectively (perioperative mortality, 3%; morbidity, 17%). Pathologic complete response occurred in 19% of patients with tumor resection. In patients with tumor resection, downstaging to N0–1 at surgery was prognostic and significantly prolonged event-free survival (EFS) and overall survival (OS; P = .0001). At median follow-up of 32 months, the median EFS and OS were 14.8 months (range, 2.4 to 53.4) and 33 months (range, 2.4 to 53.4), respectively. Local relapse occurred in 27% of patients with tumor resection, with distant metastases in 37%. Multivariate analyses identified mediastinal clearance (hazard ratio, 0.22; P = .0003) and complete resection (hazard ratio, 0.26; P = .0006) as strongly prognostic for increased survival.

Conclusion: Neoadjuvant docetaxel-cisplatin is effective and tolerable in stage IIIA pN2 NSCLC. Resection is recommended only for patients with mediastinal downstaging after chemotherapy.

Supported by an unrestricted grant used for part of the trial data management from Aventis Pharmaceuticals, Zurich, Switzerland.

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