Irinotecan (I), carboplatin (C), and radiotherapy (RT) followed by bevacizumab (B) in the treatment of limited-stage small cell lung cancer (SCLC): A phase II trial of the Minnie Pearl Cancer Research Network

Abstract

7050 Background: Preclinical studies have demonstrated VEGF expression in SCLC, a target that may predict response to treatment with anti-angiogenic agents such as B. Few trials have incorporated these agents into the treatment of SCLC, providing rationale for studying B in addition to chemoradiotherapy. Methods: The primary endpoints of this multicenter phase II study were to assess the safety and response rate (RR) of I/C/RT followed by B in patients (pts) with limited-stage SCLC. Treatment consisted of: C AUC=5 IV D1, I 50mg/m2 IV D1, 8 Q 21D for 4 cycles, and concurrent RT 1.8 Gy QD to a total of 61.2 Gy, beginning with the 3rd cycle. 3rd and 4th cycles were 28D each. Pts were restaged after 4 cycles. Pts without progression or undue toxicity received B 10 mg/kg IV Q 14D for 10 doses. Eligibility criteria included: measurable disease, ECOG PS 0–1, adequate organ function, <500mg/24 hour proteinuria, informed consent, and absence of active brain metastases, or hemoptysis. Results: Forty-one pts were enrolled between 08/03 and 09/04. The range of follow-up is 2–14 months. Baseline characteristics include: median age 66 years (42–78); male/female, 35%/65%; ECOG PS 0,1,2: 29%/66%/5%. Grade (G)3/4 non-hematologic toxicity included: hypertension (5%), diarrhea (11%), DVT (5%), vomiting (13%), and fatigue (11%). G3/4 hematologic toxicity included: neutropenia (37%), anemia (0%), and thrombocytopenia (16%). There were no treatment-related deaths, however, 2 pts came off study for dyspnea possibly related to treatment. Response data are available for 37 pts. Complete/partial RR were observed in 12 pts (32%)/18 pts (49%), respectively, for an overall RR of 81%. Eleven percent of pts had stable disease, and no pts have had disease progression (3 pts were unevaluable.) Six-month progression-free (PFS) and overall survival (OS) were 92% and 87%, respectively. One-year PFS and OS will be presented at ASCO. Conclusions: I/C/RT followed by B is a safe and well-tolerated regimen with acceptable RR in the treatment of limited-stage SCLC. One-and two-year PFS and OS will be important in estimating the impact of B in the treatment of SCLC. No significant financial relationships to disclose.