Background

Although data from preclinical and clinical studies provide a strong rationale for combining capecitabine with anti-angiogenic agents, clinical development of this fluoropyrimidine in combination with aflibercept has lagged behind other treatments. We conducted a nonrandomized, noncomparative, 2-arm, phase I trial to address this unmet need.

Patients and Methods

Patients with chemorefractory gastrointestinal and breast cancer were sequentially recruited into a continuous (Arm A, starting dose 1100 mg/m²/day) or intermittent (Arm B, 2 weeks on/1 week off, starting dose 1700 mg/m²/day) capecitabine dosing arm. Aflibercept was administered at a flat dose of 6 mg/kg every 3 weeks in both arms. A classical 3 + 3, dose-escalation design was used. The primary objective was to establish the maximum tolerated dose, dose-limiting toxicities (DLTs), and recommended dose for phase II trials.

Results

Thirty-eight eligible patients were recruited of whom 33 were assessable for DLTs (15 in arm A and 18 in arm B). Fourteen had colorectal cancer, 8 gastric cancer, and 11 breast cancer. DLTs included grade 2 hand-foot syndrome, grade 2 anorexia considered unacceptable by the patient, and grade 3 hypertension. The recommended dose for phase II trials for capecitabine was established at 1300 mg/m²/day in Arm A and 2500 mg/m²/day in Arm B with treatment-related grade ≥ 3 adverse events occurring in 47% and 50% of patients, respectively. Among 26 assessable patients, the objective response rate was 15.4% in Arm A and 7.7% in Arm B.

Conclusion

Combining capecitabine with aflibercept is feasible and associated with a manageable safety profile and some anti-tumor activity in patients with chemorefractory gastrointestinal and breast cancer.

中文翻译：

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MOMENTUM：一项研究卡培他滨和阿柏西普治疗胃肠癌和乳腺癌患者的 I 期试验。

背景

尽管来自临床前和临床研究的数据为卡培他滨与抗血管生成药物联合使用提供了强有力的理由，但这种氟嘧啶与阿柏西普联合的临床开发落后于其他治疗方法。我们进行了一项非随机、非比较、2 组 I 期试验，以解决这一未满足的需求。

患者和方法

患有化学难治性胃肠道和乳腺癌的患者被依次招募到连续（A 组，起始剂量 1100 mg/m ² /天）或间歇（B 组，2 周开始/1 周关闭，起始剂量 1700 mg/m ² / 天） ) 卡培他滨给药组。在双臂中每 3 周以 6 mg/kg 的固定剂量给予阿柏西普。使用了经典的 3 + 3 剂量递增设计。主要目标是确定最大耐受剂量、剂量限制性毒性 (DLT) 和 II 期试验的推荐剂量。

结果

招募了 38 名符合条件的患者，其中 33 名可进行 DLT 评估（A 组 15 名，B 组 18 名）。14 人患有结直肠癌，8 人患有胃癌，11 人患有乳腺癌。DLT 包括 2 级手足综合征、患者认为不可接受的 2 级厌食症和 3 级高血压。卡培他滨 II 期试验的推荐剂量在 A组确定为 1300 mg/m ² /天，在 B 组确定为2500 mg/m ² /天，治疗相关的 ≥ 3 级不良事件发生率为 47% 和 50%患者，分别。在 26 名可评估患者中，A 组的客观缓解率为 15.4%，B 组的客观缓解率为 7.7%。

结论

将卡培他滨与阿柏西普联合使用是可行的，并且在化疗难治性胃肠癌和乳腺癌患者中具有可控的安全性和一些抗肿瘤活性。