In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 25, No. 18_suppl ( 2007-06-20), p. 14118-14118
Abstract:
14118 Background: Pazopanib is a potent and selective multi-targeted receptor tyrosine kinase inhibitor of VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-a/β, and c-kit. Pazopanib also is a moderate inhibitor of CYP2C8 and CYP3A4 in vitro. Paclitaxel (T), a substrate for CYP2C8 and CYP3A4, administered alone and in combination with carboplatin (Cb) is highly active in breast, NSCLC, and ovarian cancers. The additive benefit of the anti-VEGF agent bevacizumab with T or T-Cb in breast and NSCLC provides strong rationale for use of a multi-targeted TKI with T or T-Cb. Methods: Pts with advanced cancer (ECOG PS 0–1) were eligible. Dose escalation was split into Part 1 [T (15–80 mg/m 2 ) days 1, 8, 15 q 28 days plus pazopanib (400–800 mg) QD starting on day 2 of cycle 1] and Part 2 [T (80- 225 mg/m 2 ) plus Cb AUC 6 q 21 days plus pazopanib 800 mg QD starting on day 2 of cycle 1]. Safety, PK, and clinical response were evaluated. Dose escalation occurred in cohorts of 3–6 pts based on dose-limiting toxicities (DLTs) and PK. Results: 12 pts in Part 1 received the following pazopanib/T doses (n = pts): 400 mg /15 mg/m 2 (3), 800 mg/15 mg/m 2 (3), 800mg /50 mg/m 2 (3), 800mg /80 mg/m 2 (3). Preliminary data were available from 9 pts in Part 1. Selected mean PK results for T are shown. 4 pts in Part 2 received 800mg /175 mg/m 2 /AUC 6 of pazopanib/T/Cb (data not yet available). Most common AEs ( 〉 20%) in Part 1 were Gr 1/2 and consisted of fatigue, diarrhea, anorexia, nausea, vomiting, dysgeusia, AST elevation, rash, hypertension, and cough; Gr 3 diarrhea was reported in 1 pt. The 800mg pazopanib/80 mg/m 2 T cohort in Part 1 is being expanded to 6 pts due to a DLT (dose delay of 〉 2 wks due to an abscess). Best response (n=6 pts) in Part 1 was SD (83%) (range 1–5 cycles). Conclusions: Concomitant administration of pazopanib increased paclitaxel mean Cmax and AUC(0–8) approximately 20–35%. Determination of the MTR in Parts 1 and 2 is ongoing. These findings warrant further studies at therapeutic doses of pazopanib, paclitaxel, and carboplatin. [Table: see text] No significant financial relationships to disclose.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2007.25.18_suppl.14118
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2007
detail.hit.zdb_id:
2005181-5
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