Induction (Ind), gemcitabine (G), docetaxel (D) and cisplatin (C) plus concurrent (Con) chemotherapy with thoracic radiotherapy (TRT) in stage III non-small cell lung cancer (NSCLC)

Abstract

7589 Background: New Phase III Intergroup Trial RTOG 0412 was testing induction chemoradiotherapy with cisplatin and docetaxel followed by surgical resection in stage IIIA N2. Our Institution demonstrated in a phase I study that the doses of induction chemotherapy GDC triple are D (30 mg/m2), C (35 mg/m2) and G (1,000 mg/m2) every 3 weeks. In present phase II trial we evaluated toxicity and activity of GDC Ind plus Con with TRT in stage III NSCLC. Methods: Chemotherapy-naïve pts with stage IIIA-N2 and IIIB (T4, N1-N2 only, except malignant pleural effusion) NSCLC were eligible. All drugs, G (1,000 mg/m2), C (35 mg/m2), D (30 mg/m2), were given on days 1 and 8, q21 days up to 2 cycles followed by Con: for stage IIIA, N2 non-bulky C 50 mg/m2 on days 1 and 8 q21 days for 2 cycles, and D 20 mg/m2/week x5; for stage IIIA N2 bulky and IIIB, C 50 mg/m2 on days 1 and 8, and etoposide 50 mg/m2 day 1 through 5, q28 days for 2 cycles. Patient with resectable disease at reevaluation after TRT 45 Gy on T and N fields, underwent surgical resection. Otherwise completed TRT (uninterrupted) till to 61,2 Gy. Results: From Jan ‘06 to Sep ‘07 43 eligible pts were enrolled. The characteristics were: median age 58 years (range 40–75), male/female ratio 32/11, 8 pts never smokers, stage IIIA N2 non-bulky/N2 bulky/IIIB 6/14/23. All pts had ECOG PS 0–1 at study entry. Histology was: 10 adenocarcinoma, 17 squamous-cell, 14 undifferentiated and 2 with mixed histology. 60% of 42 evaluable pts for response had an OR after Ind. Nineteen responding patients, including 9 IIIB cases and 10 IIIA, underwent radical surgery. The pathologic CR rate in the mediastinal lymph nodes has been obtained in 58%. Fourteen patients (33%) were not resectable and received full dose TRT. Ind therapy was well tolerated with 7 pts experiencing disease progression. Gr 3 toxicities during Con therapy were anemia (15%), neutropenia (16%), esophagitis (9%), fatigue (9%). The PFS and MST are not mature enough to estimate as only 14 deaths have occurred. Conclusions: These preliminary data suggest that this Ind chemotherapy and Con chemoradiotherapy regimens are active and well tolerated in locally advanced NSCLC. Response to induction chemotherapy may have major prognostic significance. No significant financial relationships to disclose.