A phase III study of Æ-941 with induction chemotherapy (IC) and concomitant chemoradiotherapy (CRT) for stage III non-small cell Lung cancer (NSCLC) (NCI T99–0046, RTOG 02–70, MDA 99–303): An interim report of toxicity and response

Abstract

7144 Background: Æ-941(Neovastat, Aeterna Laboratories) is a standardized shark cartilage extract with antiangiogenic properties (inhibition of VEGF signaling and MMP activity, induction of endothelial cell apoptosis). An ongoing placebo-controlled trial is testing Æ-941, with IC and CRT, in unresectable stage III NSCLC. Methods: Eligibility criteria include performance status (PS) < 2, weight loss < 10%. Subjects receive one of two treatment regimens depending on site of enrollment: carboplatin (C) (AUC 6) and paclitaxel (P) (200 mg/m2) x 2 cycles followed by CRT (60 Gy/30 fractions) with weekly C (AUC 2) and P (45 mg/m2) x 6 doses or cisplatin (CDDP) (75 mg/m2, d1) and vinorelbine (V) (30 mg/m2, d1 and 8) x 2 cycles followed by CRT (60 Gy/30 fractions) with CDDP (75 mg/m2, day 1) and V (15 mg/m2, d1 and 8) x 2 cycles. Æ-941 or placebo (120 ml orally twice daily) is started with IC and continued after CRT as maintenance therapy. Planned sample size: 756. Results: A data safety board review of the first 40 patients who completed CRT was performed in 4/02. Excess or differential toxicity between the Æ-941 and placebo arms was not observed. Between 6/00 and 11/04, 341 subjects have been randomized. Blinded overall toxicity data are available on 179 and 172 subjects during IC and CRT, respectively. Subject characteristics (N=179): 60% male, median age 62 years (range 41–81), 47% PS 0, 54% stage IIIB. Grade 3 or 4 hematologic toxicities (IC/CRT) included: granulocytopenia (22%/1%), leukopenia (2%/4%), thrombocytopenia (1%/3%), anemia (1%/0%), neutropenic fever (5%/2%). The most common grade 3 or 4 non-hematologic toxicities during IC were fatigue (4%), hyperglycemia (3%), and dyspnea (2%). The most common grade 3 or 4 non-hematologic toxicities during CRT were esophagitis (17%) and dyspnea/pneumonitis (5%). The following blinded response data after IC and CRT are available for 233 and 214 subjects, respectively (IC/CRT): PR+CR 35%/39%, SD 57%/48%, PD 8%/13%. Conclusions: Interim overall toxicity observed in this trial appears acceptable. Accrual to this NCI-sponsored intergroup study continues. No significant financial relationships to disclose.