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J Thorac Cardiovasc Surg 2006;131:314-321
© 2006 The American Association for Thoracic Surgery


General Thoracic Surgery

Multimodality treatment of unresectable stage III non–small cell lung cancer: Interim analysis of a phase II trial with preoperative gemcitabine and concurrent radiotherapy

Domenico Galetta, MD a , Alfredo Cesario, MD b , g , * , Stefano Margaritora, MD b , Venanzio Porziella, MD b , Alessio Piraino, MD b , Rolando M. D'Angelillo, MD c , Maria A. Gambacorta, MD c , Sara Ramella, MD c , Lucio Trodella, MD c , Salvatore Valente d , Giuseppe M. Corbo d , Giuseppe Macis e , Antonino Mulè f , Vittorio Cardaci, MD h , Silvia Sterzi, MD i , Pierluigi Granone, MD b , Patrizia Russo, PhD b

a Department of Thoracic Surgery, European Institute of Oncology, Milan
b Division of General Thoracic Surgery, Catholic University, Rome
c Department of Radiotherapy, Catholic University, Rome
d Division of Respiratory Physiology, Catholic University, Rome
e Department of Radiology, Catholic University, Rome
f Department of Pathology, Catholic University, Rome
g Clinical, Respiratory Pathology Translational Laboratory, San Raffaele, IRCCS, Rome
h Department of Pulmonary Rehabilitation, San Raffaele, IRCCS, Rome
i Rehabilitation Service, University Campus Bio-Medico, Rome, Italy.

Read at the Thirtieth Annual Meeting of the Western Thoracic Surgical Association, Maui, Hawaii, June 23-26, 2004.

Received for publication June 19, 2005; revisions received July 2, 2005; accepted for publication July 11, 2005.

* Address for reprints: Alfredo Cesario, MD, Division of General Thoracic Surgery, Catholic University, Largo A. Gemelli, 8, 00168 Rome, Italy. (Email: alfcesario{at}rm.unicatt.it).

OBJECTIVE: We report the preliminary results of a phase II trial undertaken to determine the feasibility and efficacy of gemcitabine and concurrent radiotherapy in patients with inoperable stage III non–small cell lung cancer.

METHODS: Between February 2001 and June 2003, a total of 46 patients (37 male and 9 female, median age 64 years) with clinical stage III non–small cell lung cancer (41 cIIIA and 5 cIIIB) were enrolled in a combined chemoradiation protocol with gemcitabine as the chemotherapeutic agent. Gemcitabine (350 mg/m2) was administered weekly for 5 consecutive weeks as a 30-minute intravenous infusion before radiotherapy (total dose 50.4 Gy, 1.8 Gy/d). Toxicity was routinely assessed. Those patients with disease judged to be resectable at restaging underwent surgery.

RESULTS: Toxicity was moderate, with the exception of 1 grade 3 thrombocytopenia. All but 5 patients were available for restaging. No complete responses were observed. Thirty-four patients (82.9%) had partial responses, 5 (12.2%) had stable disease, and 2 (4.9%) had progressive disease. Twenty-nine of 46 patients (63%, 27 cIIIA and 2 cIIIB) underwent surgery. Radical resection was possible in all cases. Surgery included 17 lobectomies, 4 bilobectomies, and 8 pneumonectomies. There were no deaths. Morbidity was 13.8% (4/29). Pathologic downstaging to stage 0 or I was observed in 18 patients (39%, 18/46). After a median follow-up of 13 months (range 2-28 months), 24 of the patients who had undergone operation (86.2%) were alive, with a median disease-free survival of 16 months. Overall 2-year survival was 66.1%, with a significant difference between resected and unresected disease (82% vs 36%, P = .0002).

CONCLUSION: The results of this induction trial confirm the feasibility and the efficacy of gemcitabine with concurrent radiotherapy.



Abbreviations and Acronyms CT = computed tomography; NSCLC = non–small cell lung cancer; PD = progressive disease; PR = partial response; SD = stable disease





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