Intratumoral chemotherapy with paclitaxel liposome combined with systemic chemotherapy: a new method of neoadjuvant chemotherapy for stage III unresectable non-small cell lung cancer.

The aim of the study was to evaluate the efficacy and safety of intratumoral chemotherapy with paclitaxel liposome combined with systemic chemotherapy as induction therapy in clinical stage III unresectable non-small cell lung cancer (NSCLC). Between January 2011 and July 2014, 48 patients, stage III, performance status 0-1, with unresectable clinical stage IIIA or IIIB NSCLC suitable for definitive radiation treatment, were included in the study. Patients with T3N1M0 and T4 (ipsilateral lung nodules) N0-1M0 were not included. Patients were given 3 cycles of chemotherapy every 3 weeks. Carboplatin (AUC5 by i.v. on day 1) and gemcitabine (i.v. 1,000 mg/m(2) on days 1 and 8) were administered. Paclitaxel liposome was injected at 1-3 mg/ml concentration into the tumor lesion by computed tomography-guided percutaneous fine-needle intratumoral injection and proven malignant lymph nodes according to pretreatment histological/cytological results by endobronchial ultrasound drug delivery with a needle on day 1 and day 8. Toxicity was assessed on days 8 and 22 in each cycle. Overall response rate (ORR) evaluation was performed at the end of cycle 3. Out of the 48 enrolled patients, 28 were males and 20 females, 19 patients had stage IIIA and 29 stage IIIB NSCLC. Thirty-six partial responses and two complete responses were observed, for an ORR of 81 %. The most frequent G3-G4 toxicity included neutropenia (in 15 % of cases), hypertransaminasemia (6 %), and diarrhea (4 %). A median PFS of 16.5 months (95 % CI 13.7-19.2) and median OS of 23.2 months (95 % CI 20.0-26.3) were observed. Eleven stage IIIA patients underwent surgery, for a resection rate of 58 %. Intratumoral chemotherapy with paclitaxel liposome combined with systemic chemotherapy demonstrated a considerable disease response and resection rate, with acceptable toxicity.