A phase I study of sirolimus and bevacizumab in patients with advanced malignancies

被引：16

作者：

Cohen, E. E. W. ^{[1
]}

Sharma, M. R. ^{[1
]}

Janisch, L. ^{[1
]}

Llobrera, M. ^{[1
]}

House, L. ^{[1
]}

Wu, K. ^{[1
]}

Ramirez, J. ^{[1
]}

Fleming, G. F. ^{[1
]}

Stadler, W. M. ^{[1
]}

Ratain, M. J. ^{[1
]}

机构：

[1] Univ Chicago, Dept Med, Sect Hematol & Oncol, Comprehens Canc Ctr,Comm Clin Pharmacol & Pharmac, Chicago, IL 60637 USA

来源：

EUROPEAN JOURNAL OF CANCER | 2011年 / 47卷 / 10期

关键词：

Sirolimus; Bevacizumab; Phase I; MOUSE MODEL; RAPAMYCIN; PHARMACOKINETICS; EVEROLIMUS; CARCINOMA; MTOR;

D O I：

10.1016/j.ejca.2011.02.017

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: We performed a single institution, phase I study of sirolimus and bevacizumab, in order to determine the dose limiting toxicity (DLT) and recommended phase II doses. Patients and methods: Eligible patients had previously treated advanced malignancies and were enrolled in three cohorts. Sirolimus 90 mg PO weekly (45 mg on days 1 and 2) was combined with bevacizumab 7.5 mg/kg (cohort #1) or bevacizumab 15 mg/kg (cohort #2) IV g3weeks. Sirolimus 4 mg PO daily was combined with bevacizumab 15 mg/kg IV q3weeks (cohort #3). Results: Twenty-eight patients enrolled. The most common tumour types were colorectal (21%), head/neck (14%), and renal cell (11%). No DLTs were observed in cohorts #1 (4 patients) and #2 (12 patients), while two DLTs (grade 3 confusion and grade 3 fatigue) were observed in the first six patients in cohort #3 (12 patients). The most common grade 3 toxicities were fatigue (18%), hypertension (14%) and anorexia (11%). There were no responses, but one patient has had stable disease for 78 weeks. Conclusions: The combination of sirolimus and bevacizumab at full doses is tolerable in the majority of patients. The availability and cost of sirolimus compared with other mTOR inhibitors make this an attractive agent to combine with bevacizumab. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：1484 / 1489

页数：6

共 21 条

[1] Phase II trial of bevacizumab (B) plus everolimus (E) for refractory metastatic colorectal cancer (mCRC). [J].