Phase 1 study of cetuximab in combination with 5-fluorouracil, cisplatin, and radiotherapy in patients with locally advanced anal canal carcinoma

被引:50
|
作者
Olivatto, Luis O. [1 ]
Vieira, Fernando M. [4 ]
Pereira, Bruno V. [1 ]
Victorino, Ana P. [4 ]
Bezerra, Marcos [2 ]
Araujo, Carlos M. [2 ]
Erlich, Felipe [2 ]
Faroni, Lilian [2 ]
Castro, Leonaldson [3 ]
Lusis, Edward C. [3 ]
Marins, Alessandra [4 ]
Ferreira, Carlos Gil [4 ]
机构
[1] Hosp Inst Nacl Canc, Div Clin Oncol, Rio De Janeiro, Brazil
[2] Hosp Inst Nacl Canc, Div Radiat Oncol, Rio De Janeiro, Brazil
[3] Hosp Canc, Inst Nacl Canc, Div Surg Oncol, BR-20231050 Rio De Janeiro, Brazil
[4] Inst Nacl Canc, Rio De Janeiro, Brazil
关键词
locally advanced anal canal carcinoma; cetuximab; chemoradiation; 5-fluorouracil; cisplatin; GROWTH-FACTOR RECEPTOR; THROMBOEMBOLIC EVENTS; RADIATION-THERAPY; VENOUS THROMBOEMBOLISM; RISK-FACTORS; MITOMYCIN-C; I TRIAL; CANCER; CHEMOTHERAPY; METAANALYSIS;
D O I
10.1002/cncr.28045
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND: This study sought to determine the feasibility and recommended phase 2 dose (RP2D) of the combination of cetuximab with chemoradiotherapy based on 5-fluorouracil (5-FU) and cisplatin (CP) in locally advanced anal canal carcinoma. METHODS: Cetuximab was administered on days 1, 8, 15, 29, 36, 43, and 50 (400 mg/m(2) initial dose, then 250 mg/m(2)/week) concurrent with total dose radiation of 55 to 59 Gy, both starting on day 1. Escalating doses of 5-FU (96-hour infusion) and CP (2-hour infusion), both on days 1 and 29, were administered according to the following design: starting dose level (0) 5-FU/CP5800/60 mg/m(2)/day and up to dose level (12) 5-FU/CP51000/80 mg/m(2)/day. RESULTS: Dose-limiting toxicity (DLT) events (uncontrolled diarrhea or febrile neutropenia) occurred in 3 of 14 assessable patients receiving escalated dose of 5-FU/CP, with 1 in dose level (0) and 2 in dose level (12). The RP2D was 5-FU/CP5800/80 mg/m(2)/day. Because of unexpected non-DLT treatment-related grade 3 (G3) adverse events (AEs) such as thrombosis/embolism, syncope, and infection occurring in >= 20% of patients, a safety expansion cohort with an additional 9 patients was investigated with the RP2D. The most frequent G3/G4 AEs evaluated in 23 patients were radiation dermatitis (12 patients), diarrhea (10 patients), thrombosis/embolism (6 patients), and infection (5 patients). The study was closed due to these severe AEs, although no G5 AEs occurred. Twenty of 21 patients (95%) achieved pathological complete response at primary tumor. With a median follow-up of 43.4 months, the 3-year locoregional control rate was 64.2%. CONCLUSIONS: Cetuximab could not be integrated with chemoradiotherapy-cisplatin-based therapy due to the high toxicity rate. However, efficacy is encouraging and further investigation of an epidermal growth factor receptor-targeted agent (other than cetuximab) concurrent with chemoradiation should be pursued. Cancer 2013; 119: 2973-80. (C) 2013 American Cancer Society.
引用
收藏
页码:2973 / 2980
页数:8
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