Phase I study of irinotecan (Ir) and cisplatin (DDP) in combination with thoracic radiotherapy (RT), either twice daily (45 Gy) or once daily (70 Gy), in patients with limited (Ltd) small cell lung carcinoma (SCLC): Early analysis of RTOG 0241

7058 Background: Ir in combination with DDP has proven superior to DDP & VP-16 in extensive stage SCLC (Noda et al NEJM 1/02), with marked increase in 2 yr survival (19.5%, vs 5.2%). Hence, it is critical to determine if Ir can be safely & effectively integrated with concurrent RT and DDP in earlier stage, Ltd SCLC. Methods: 1° endpoint: Determine maximum tolerated dose (MTD) of Ir d 1 & 8 plus DDP 60 mg/m2 q 3 wks & either BID RT (45 Gy) or QD RT (70 Gy). Eligibility stipulated Tx-naïve patients (pts) with Ltd SCLC, PS 0–1, adequate heme (ANC ≤ 1500/mL; plts ≥ 120,000/mL) hepatic (bili ≤ 1.5/dL) & renal (creat ≤ 1.5gr/dL) function, & baseline FEV1 of ≥ 1 liter. Ir was escalated in sequential (seq) cohorts from 40 mg/m2 (level 1) to 50 mg/m2 (level 2) & then to 60 mg/m2 (level 3) d 1 & 8 q 3 wks during each cycle of treatment. Ir & DDP were given concurrently with RT for cycle 1 in seq A (45 Gy) & during cycles 1 & 2 in seq B (70 Gy). 36 pts were targeted for accrual. DLT was defined as gr 4 esophagitis, pneumonitis, or diarrhea; gr 4 neutropenic fever, or any attributable gr 5 toxicity Results: As of 12/05, 36 pts were accrued, (21 - seq A; 15 - seq B). Median age was 64 (range 49–79) Of 33 eval pts, 18 (55%) were female; 24 (73%) PS 0; 67% had ≤ 5% wt loss. Attributable DLT was not seen in seq A, but was observed in seq B (70 Gy) at 50 mg/m2 with 1 episode each of gr 4 diarrhea & esophagitis, necessitating hospitalization. In addition, 1 pt in seq B had non-attributable gr 4 cardiovascular AEs. There has been no acute gr 5 toxicity. 1 pt experienced late gr 3 pulm toxicity, another gr 3 constitutional toxicity, including wt loss. The overall incidence of gr 3 esophagitis was 34%. Conclusions: In Ltd SCLC, I at 60 mg/m2 d 1 & 8 is safe & feasible in combination with DDP 60 mg/m2 q 3 wks & BID RT (45 Gy). The MTD for I in combination with RT (70 Gy) & DDP 60 mg/m2 is 40 mg/m2 d 1 and 8. Response, progression, survival data remain immature. [Table: see text] [Table: see text]