Phase II trial of induction high-dose chemotherapy followed by surgical resection and radiation therapy for patients with marginally resectable non-small cell carcinoma of the lung

The combination of carboplatin and paclitaxel is an active regimen in non-s mall cell lung cancer (NSCLC). Historically patients with stage III disease have manifested higher response rates than patients with metastatic diseas e, and patients achieving a pathologic complete response to induction chemo radiation therapy prior to surgery have shown better long-term outcome. Bas ed upon our pilot data using high-dose carboplatin and paclitaxel, we desig ned a phase II trial in patients with marginally resectable stage IIIA NSCL C. Ten patients, with bulky nodal stage IIIA disease, initially received et oposide (2 g/m(2)) and granulocyte colony-stimulating factor (G-CSF) to mob ilize peripheral blued stern cells (PBSC). Two cycles, 28 days apart, of ca rboplatin (AUC 12 in seven patients; AUC 16 in three patients) and paclitax el (250 mg/m(2)) were administered with filgrastim (5 mu g:kg) and PBSC sup port. After re-evaluation. patients underwent a thoracotomy followed by rad iotherapy (44-60 Gy) if deemed resectable, or radiotherapy alone (60 Gy) if not resectable. The median age was 58.5 years (48-66) with a median ECOG p erformance status of 0 (0-1). Histology was adenocarcinoma in seven patient s; the remainder had either squamous cell, large cell or bronchoalveolar ca rcinoma. Based on CT radiography, the Overall response rate was 40%. Eight of ten patients underwent resection with four right pneumonectomies. three right upper lobectomies and one wedge resection of the right upper lobe. Si x patients had a complete resection, Of eight patients resected, four were downstaged by induction therapy, three remained unchanged and one was found to have more extensive disease. The remaining two patients developed metas tatic disease while receiving chemotherapy. The median dose of postoperativ e radiotherapy was 54 Gy (35-66 Gy). Actual median follow-up for all patien ts was 89 weeks (25 to 136 +). The actuarial median overall survival was 12 4 weeks (25 to 136 +) and time to progression was 57 weeks (17 to 136 +), T he median dose of carboplatin delivered expressed as mg/m(2) was 779 (615- 1540). Neutropenic fever occurred in two patients during the initial mobili zation cycle only. The median number of units of RBC and/or platelets trans fused was 0 (0-2 and 0-6, respectively). There were no significant non-hema tologic toxicities. High-dose induction chemotherapy with stem cell rescue is feasible and safe with an acceptable response rate. Thoracotomy, includi ng pneumonectomy and postoperative radiotherapy. were well tolerated by pat ients after undergoing high-dose induction chemotherapy with no apparent in crease in peri-operative morbidity. The pathologic complete response rate w as low - one out of ten patients. These results indicate that dose escalati on of induction chemotherapy does not improve response rates even in this h ighly selected patient population. Accordingly, the complexity and potentia l toxicity of high-dose chemotherapy as delivered in this trial as neoadjuv ant treatment of non-small cell lung cancer, is not warranted, (C) 2000 Els evier Science Ireland Ltd. All rights reserved.