In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 25, No. 18_suppl ( 2007-06-20), p. 7654-7654
Abstract:
7654 Background: Vandetanib (ZD6474) is a once-daily oral anticancer drug that selectively inhibits VEGF-dependent tumor angiogenesis and EGFR- and RET-dependent tumor cell proliferation and survival. Methods: Eligible patients had locally advanced or metastatic NSCLC (stage IIIB/IV) after failure of 1 st -line chemotherapy. An initial cohort of 10 patients received once- daily oral vandetanib (100 mg) with pemetrexed (500 mg/m 2 i.v. infusion every 21 days). If 〈 2 patients experienced a vandetanib- related dose-limiting toxicity (DLT), an additional cohort received vandetanib 300 mg + pemetrexed. The planned duration of treatment was =6 weeks. The primary objective of the study was to establish the safety and tolerability of vandetanib + pemetrexed. Secondary objectives included an assessment of pharmacokinetic (PK) interaction and preliminary assessment of efficacy (RECIST). Results: Twenty- one patients (14 male, 7 female; mean age 60 years, range 44–77) received vandetanib 100 mg + pemetrexed (n=10) or vandetanib 300 mg + pemetrexed (n=11). One DLT was reported in each cohort: QTc prolongation ( 〉 100 ms from baseline, but absolute QTc 〈 500 ms) in a male patient who had electrolyte imbalance and short baseline QTc interval of 318 ms (100 mg cohort); and interstitial lung disease, which resolved after steroid therapy, in a Caucasian female patient with bronchoalveolar carcinoma and a long smoking history (300 mg cohort). The most common adverse events (AEs) were rash, anorexia, fatigue and diarrhea (all n=10; 48%). The most frequent CTC grade 3/4 AEs were increased gamma-glutamyltransferase (n=4), anorexia (n=3) and dyspnea (n=3), which are generally consistent with previous experience with vandetanib and pemetrexed as monotherapies. There was no apparent PK interaction between vandetanib and pemetrexed. In 18 patients evaluable for efficacy, there was one confirmed partial response (female; 100 mg cohort) and 13 stable disease =6 weeks. Conclusions: In patients with advanced NSCLC, vandetanib + pemetrexed was generally well tolerated, with no apparent PK interaction. A Phase III trial of vandetanib 100 mg + pemetrexed in 2nd-line NSCLC has begun. No significant financial relationships to disclose.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2007.25.18_suppl.7654
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2007
detail.hit.zdb_id:
2005181-5
