当前位置： SCI文献检索 > BRITISH JOURNAL OF CANCER期刊下所有文献 > A phase I/II trial of sorafenib and infliximab in advanced renal cell carcinoma.

A phase I/II trial of sorafenib and infliximab in advanced renal cell carcinoma.

Abstract：

BACKGROUND:There is clinical evidence to suggest that tumour necrosis factor-α (TNF-α) may be a therapeutic target in renal cell carcinoma (RCC). Multi-targeted kinase inhibitors, such as sorafenib and sunitinib, have become standard of care in advanced RCC. The anti-TNF-α monoclonal antibody infliximab and sorafenib have differing cellular mechanisms of action. We conducted a phase I/II trial to determine the safety and efficacy of infliximab in combination with sorafenib in patients with advanced RCC. METHODS:Eligible patients were systemic treatment-naive or had received previous cytokine therapy only. Sorafenib and infliximab were administered according to standard schedules. The study had two phases: in phase I, the safety and toxicity of the combination of full-dose sorafenib and two dose levels of infliximab were evaluated in three and three patients, respectively, and in phase II, further safety, toxicity and efficacy data were collected in an expanded patient population. RESULTS:Acceptable safety was reported for the first three patients (infliximab 5 mg kg⁻¹) in phase 1. Sorafenib 400 mg twice daily and infliximab 10 mg kg⁻¹ were administered to a total of 13 patients (three in phase 1 and 10 in phase 2). Adverse events included grade 3 hand-foot syndrome (31%), rash (25%), fatigue (19%) and infection (19%). Although manageable, toxicity resulted in 75% of the patients requiring at least one dose reduction and 81% requiring at least one dose delay of sorafenib. Four patients were progression-free at 6 months (PFS₆ 31%); median PFS and overall survival were 6 and 14 months, respectively. CONCLUSION:Sorafenib and infliximab can be administered in combination, but a significant increase in the numbers of adverse events requiring dose adjustments of sorafenib was observed. There was no evidence of increased efficacy compared with sorafenib alone in advanced RCC. The combination of sorafenib and infliximab does not warrant further evaluation in patients with advanced RCC.

journal_name

Br J Cancer

journal_title

British journal of cancer

authors

Larkin JM,Ferguson TR,Pickering LM,Edmonds K,James MG,Thomas K,Banerji U,Berns B,de Boer C,Gore ME

doi

10.1038/sj.bjc.6605889

subject

Has Abstract

pub_date

2010-10-12 00:00:00

pages

1149-53

issue

eissn

0007-0920

issn

1532-1827

pii

6605889

journal_volume

103

pub_type

杂志文章

在线工具

A phase I/II trial of sorafenib and infliximab in advanced renal cell carcinoma.