A randomized, double‐blind, phase 2 trial of platinum therapy plus etoposide with or without concurrent vandetanib (ZD6474) in patients with previously untreated extensive‐stage small cell lung cancer: Hoosier Cancer Research Network LUN06‐113. Issue 2 (1st September 2016)

• Record Type: Journal Article
• Authors: Sanborn, Rachel E.; Patel, Jyoti D.; Masters, Gregory A.; Jayaram, Nagesh; Stephens, Anthony; Guarino, Michael; Misleh, Jamal; Wu, Jingwei; Hanna, Nasser
• Is Part Of: Cancer. Volume 123:Issue 2(2017)
• Page Start: 303
• Page End: 311
• Publication Date: 2016-09-01
• Subjects: carboplatin -- cisplatin -- etoposide -- small cell lung cancer -- vandetanib; Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.30287
• Languages: English
• ISSNs: 0008-543X

Abstract

Abstract : BACKGROUND: This randomized, double‐blind, phase 2 trial evaluated whether the addition of vandetanib to platinum plus etoposide for previously untreated extensive‐stage small cell lung cancer (SCLC) prolonged the time to disease progression in comparison with chemotherapy alone. METHODS: Patients with previously untreated extensive‐stage SCLC received platinum (cisplatin or carboplatin) with etoposide in combination with vandetanib (100 mg daily) or a placebo for up to 4 total cycles (no maintenance therapy). An initial safety run‐in phase was conducted with the first 6 patients enrolled; all these patients received vandetanib with cisplatin and etoposide. With an overall sample size of 68 patients, the study had 80% power to detect a 3‐month difference in the time to progression (TTP) from 4 to 7 months (significance level, .10 [1‐sided log‐rank test]). RESULTS: Seventy‐four patients were enrolled between April 2008 and May 2013. Thirty‐three patients were ultimately randomized to each arm. The baseline characteristics were well balanced, and the median number of treatment cycles was 4 for each arm. Thirty‐one patients in each arm were evaluable for TTP; the median TTP was 5.62 months with vandetanib and 5.68 months with the placebo ( P = .9518). The median overall survival was 13.24 months with vandetanib and 9.23 months with the placebo ( P = .4577; 33 evaluable patients in each arm). Nonhematologic toxicity was increased with vandetanib versus the placebo. No correlation was seen between vascular endothelial growth factor polymorphisms and outcomes. CONCLUSIONS: The addition of vandetanib to platinum and etoposide did not improve outcomes for patients with newly diagnosed extensive‐stage SCLC. Toxicity was increased in comparison with chemotherapy alone. Cancer 2017;123:303–311. © 2016 American Cancer Society . Abstract : A randomized, placebo‐controlled, phase 2 trial is used to evaluate the combination of vandetanib with platinum and etoposide for patients with previously untreated extensive‐stage small cell lung cancer (planned maximum of 6 cycles with no maintenance therapy). With 74 patients enrolled and 33 ultimately randomized to each arm, no significant difference is demonstrated in the time to progression or median overall survival; however, there is an increase in nonhematologic toxicity with vandetanib versus a placebo.