Pathologic response after neoadjuvant carboplatin and weekly paclitaxel for early-stage lung cancer: a Brown University oncology group phase II study.

Introduction: Pathologic complete response (pCR) to neoadjuvant chemotherapy is associated with improved survival in solid tumors. Southwest Oncology Group 9,900 demonstrated a 9% pCR after three cycles of paclitaxel/carboplatin every 21 days. We evaluated pCR rate with intensive weekly paclitaxel in a phase II study.

Methods: Patients with non-small cell lung cancer, stage IB to IIIA, were eligible and received carboplatin, area under the curve = 6, every 21 days ×3 and paclitaxel 80 mg/m weekly ×9. Primary outcome was the pCR rate.

Results: Twenty patients with clinical stage IB (n = 16), IIA (n = 1), IIB (n = 1), and IIIA (n = 2) were enrolled. Mean age was 65 years. Toxicity included grade 4 neutropenia in 1 (5%), grade 3 neutropenia in 3 (15%), grade 3 neuropathy in 1 (5%), and grade 3 nausea in 1 (5%). After neoadjuvant therapy, one patient refused surgery and one died of a nontreatment-related event. Eighteen patients underwent complete resection, 15 by lobectomy, and 3 by pneumonectomy. Pathology revealed 3 (17%) patients with pCR. The median follow-up is 67 months. For clinical stage IB (n = 16), the median overall survival has not been reached, and the 5-year overall survival is 69%. All patients with pCR (n = 3) remain alive and disease-free. Improved overall survival was seen in patients who were pathologically down-staged versus patients who were not, p = 0.05.

Conclusions: Neoadjuvant chemotherapy with intensive weekly paclitaxel and carboplatin is well tolerated and does not increase surgical morbidity. This intense regimen achieves rates of pCR and survival that compares favorably with other reported induction regimens and merits further investigation.