Medical Oncology, S, Salvatore Hospital, University of L'Aquila, L'Aquila, Italy.
BMC Cancer. 2010 Oct 19;10:567. doi: 10.1186/1471-2407-10-567.
This phase II study investigated efficacy and safety of weekly alternating Bevacizumab (BEV)/Irinotecan (CPT-11) or Oxaliplatin (OHP) associated to weekly 5-Fluorouracil (5-FU) in first line treatment of metastatic colorectal carcinoma (MCRC).
Simon two-step design: delta 20% (p0 50%, p1 70%), power 80%, α 5%, β 20%. Projected objective responses (ORR): I step, 8/15 patients (pts); II step 26/43 pts. Schedule: weekly 12 h-timed-flat-infusion/5-FU 900 mg/m2, days 1-2, 8-9, 15-16, 22-23; CPT-11 160 mg/m2 plus BEV 5 mg/kg, days 1,15; OHP at three dose-levels, 60-70-80 mg/m2, days 8, 22; every 4 weeks.
Fifty consecutive, unselected pts < 75 years were enrolled: median age 63; young-elderly (yE) 24 (48%); liver metastases (LM) 33 pts, 66% Achieved OHP recommended dose, 80 mg/m2. ORR 82% intent-to-treat and 84% as-treated analysis. Median progression-free survival 12 months. Equivalent efficacy was obtained in yE pts. Liver metastasectomies were performed in 26% of all pts and in 39% of pts with LM. After a median follow-up of 21 months, median overall survival was 28 months. Cumulative G3-4 toxicities per patient: diarrhea 28%, mucositis 6%, neutropenia 10%, hypertension 2%. They were equivalent in yE pts. Limiting toxicity syndromes (LTS), consisting of the dose-limiting toxicity, associated or not to G2 or limiting toxicities: 44% overall, 46% in yE. Multiple versus single site LTS, respectively: overall, 24% versus 20%; yE pts, 37.5% versus 8%.
Poker combination shows high activity and efficacy in first line treatment of MCRC. It increases liver metastasectomies rate and can be safely administered.
Osservatorio Nazionale sulla Sperimentazione Clinica dei Medicinali (OsSC) Agenzia Italiana del Farmaco (AIFA) Numero EudraCT 2007-004946-34.
本 II 期研究旨在探讨贝伐单抗（BEV）/伊立替康（CPT-11）或奥沙利铂（OHP）联合每周氟尿嘧啶（5-FU）一线治疗转移性结直肠癌（MCRC）的疗效和安全性。
Simon 两步设计：增量 20%（p050%，p170%），效能 80%，α5%，β20%。预期客观缓解率（ORR）：I 步，15 例患者中有 8 例（pts）；II 步，43 例患者中有 26 例。方案：每周 12 小时持续输注/5-FU900mg/m2，第 1-2、8-9、15-16、22-23 天；CPT-11160mg/m2 加 BEV5mg/kg，第 1、15 天；OHP 三个剂量水平，60-70-80mg/m2，第 8、22 天；每 4 周一次。
连续入组 50 例未经选择的<75 岁患者：中位年龄 63 岁；年轻老年人（yE）24 例（48%）；33 例患者存在肝转移（LM），66%达到 OHP 推荐剂量，80mg/m2。意向治疗和治疗分析的客观缓解率（ORR）分别为 82%和 84%。中位无进展生存期为 12 个月。yE 患者获得了等效的疗效。所有患者中有 26%接受了肝转移切除术，LM 患者中有 39%接受了肝转移切除术。中位随访 21 个月后，中位总生存期为 28 个月。每位患者的累积 G3-4 毒性：腹泻 28%，黏膜炎 6%，中性粒细胞减少 10%，高血压 2%。yE 患者的毒性相当。累计毒性综合征（LTS），包括剂量限制毒性，以及 G2 或限制毒性：总体为 44%，yE 为 46%。多个与单一部位 LTS 分别为：总体，24%与 20%；yE 患者，37.5%与 8%。
扑克联合方案在转移性结直肠癌的一线治疗中具有高活性和疗效。它增加了肝转移切除术的比例，且可以安全使用。
意大利国家临床试验观察站（OsSC）意大利药品管理局（AIFA）EudraCT 编号 2007-004946-34。
