In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 4_suppl ( 2016-02-01), p. 759-759
Abstract:
759 Background: Clinical benefit of combination of panitumumab and bevacizumab (PB) based on the BBP strategy in third-line chemotherapy is unclear. There was no prospective data about the pharmacokinetic interaction between bevacizumab and panitumumab. Methods: This study composed two parts; 1) PB part: phase I study of PB to estimate its recommended dose, 2) CPB part: feasibility study to investigate the safety in combination of bevacizumab and panitumumab at the recommended dose in the phase I part with irinotecan (CPT-11) at the dose used in the prior chemotherapy. Inclusion criteria was as follows; 1) Age: ≥ 20 and 〈 76 years old, 2) performance status ≤ 1, 3) histologically colorectal adenocarcinoma with KRASwild-type, 4) patients who previously received fluoropyrimidine, oxaliplatin, CPT-11 and bevacizumab for unresectable metastatic disease. Three dose levels of panitumumab (Level 1: 6mg/kg, Level 0: 5mg/kg, Level -1: 4mg/kg) was set in PB part and starting dose level was Level 0. Bevacizumab was administered at fixed-dose of 5mg/kg regardless of dose levels of panitumumab. All drugs were administered on day1 and repeated every 2 weeks. Definition of dose limiting toxicity (DLT) was grade 4 hematological adverse events or ≥ grade3 non-hematological adverse events despite the supportive care observed in 28 days from day1 of cycle 1. Results: There were no cases showing DLT at level 0 (n = 3) and level 1 (n = 3) in the PB part and recommend dose was determined as panitumumab 6mg/kg and bevacizumab 5mg/kg. In the whole treatment course at level 1, grade 3 rash acneiform was observed in 2 patients and 2 patients achieved partial response. In six patients (CPT-11 150mg/m 2 , biweekly n = 3, 120mg/m 2 n = 3) enrolled in the CBP part, grade 3 toxicities were leukopenia/neutropenia (n = 1), mucositis (n = 1), diarrhea (n = 1), rash acneiform (n = 1), thromboembolic event (n = 1). Two out of 6 patients achieved partial response in CPB regimen. Conclusions: The recommended dose of PB regimen were panitumumab 6mg/kg and bevacizumab 5mg/kg. Combination of panitumumab and bevacizumab showed manageable toxicity. Clinical trial information: UMIN000009362.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2016.34.4_suppl.759
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2016
detail.hit.zdb_id:
2005181-5
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