Induction (Ind) plus concurrent (Con) chemotherapy with high-dose (74 Gy) 3-dimensional (3-D) thoracic radiotherapy (TRT) in stage III non-small cell lung cancer (NSCLC): Preliminary report of Cancer and Leukemia Group B (CALGB) 30105.

7042 Background: Combined chemoradiotherapy is the standard of care in stage III NSCLC. At standard TRT doses, local failures remain problematic and strategies exploiting the dose-response aspect of TRT are warranted. 3-D TRT allows escalation of TRT dose with acceptable toxicity (Socinski et al, J Clin Oncol 22:4341, 2004) and may enhance survival by improving loco-regional control.,This is a two-arm randomized phase II trial evaluating 74 Gy with Con chemotherapy: Arm A- 2 cycles of Ind carboplatin (C) (AUC 6) and paclitaxel (P) (225 mg/m) followed by weekly Con C (AUC 2/wk) and P (45 mg/m) and 74 Gy; Arm B- 2 cycles of Ind C (AUC 5) and gemcitabine (G) (1000 mg/m d1,8) followed by Con G (35 mg/m twice weekly) and 74 Gy. The primary endpoint was a survival rate of ≥50% at 18 months after treatment initiation or med survival time (MST) of ≥18 mos.,69 pts were entered (43 Arm A, 26 Arm B)- med age 61 yrs (39-77), 77% male, PS 0:1 42%:58%, stage IIIA:B 52%:48%. Ind therapy on both arms was well tolerated with no pts experiencing disease progression. ARM A- Overall response rate (RR) to all therapy was 61.9%. Gr 3-4 toxicities during Con therapy were anemia (15%), neutropenia (26%), esophagitis (9%), fatigue (9%), neuropathy (3%) and pulmonary (12%). There was 1 (3%) Gr 5 cardiac event. With med follow-up of 16.4 mos, the med progression-free survival (PFS) is 15.2 mos. The MST is not mature enough to estimate as only 15 deaths have occurred. ARM B- Closed early due to 3 (13%) Gr 5 pulmonary events. Overall RR to all therapy was 66.6%. Gr 3-4 toxicities during Con therapy were anemia (13%), fatigue (35%), esophagitis (35%), hemoptysis (4%), pulmonary (26% plus the 3 Gr 5 events). With med follow-up of 22 mos, the med PFS is 7.7 mos and the MST is 13.9 mos. There was a correlation between Gr 3-5 pulmonary toxicity and V ≥ 38% (p<0.05).,1) High dose 3-D TRT is feasible within CALGB, 2) the details of TRT (V) are important with regard to toxicity, 3) the survival of pts on Arm A appears promising. [Table: see text].