A Phase I/IIa Study of DHP107, a Novel Oral Paclitaxel Formulation, in Patients with Advanced Solid Tumors or Gastric Cancer

• Published in: The oncologist (Dayton, Ohio) Vol. 22; no. 2; pp. 129 - e8
• Main Authors: Ryu, Min‐Hee, Ryoo, Baek‐Yeol, Kim, Tae Won, Kim, Sung Bae, Lim, Hyeong‐Seok, Bae, Kyun‐Seop, Park, Sook Ryun, Jo, Yeong‐Woo, Cho, Hyun Ju, Kang, Yoon‐Koo
• Format: Journal Article
• Language: English
• Published: United States AlphaMed Press 01-02-2017
• Subjects: Adult; Aged; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Agents, Phytogenic - therapeutic use; Clinical Trial Results; Female; Humans; Male; Middle Aged; Paclitaxel - administration & dosage; Paclitaxel - pharmacology; Paclitaxel - therapeutic use; Stomach Neoplasms - drug therapy; Stomach Neoplasms - pathology
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1634/theoncologist.2016-0273

Lessons Learned
Ideally, patients should have access to an oral formulation of paclitaxel, as well as an intravenous formulation, to allow development of regimens exploring alternate schedules and to avoid reactions to Cremophor EL (BASF Corp., Ludwigshafen, Germany, https://www.basf.com).
DHP107 is a novel oral paclitaxel formulation that is a tolerable and feasible regimen for patients with gastric cancer, with data suggesting efficacy similar to that of intravenous paclitaxel.
Background
We evaluated the maximum tolerated dose (MTD) of DHP107, a novel oral paclitaxel formulation, and the efficacy and safety of the agent in patients with advanced solid tumors.
Patients and Methods
Phase I study: cohorts of 3–6 patients with advanced solid tumors received escalating DHP107 doses. Phase IIa study: patients with measurable advanced gastric cancer received DHP107, 200 mg/m2 b.i.d., on days 1, 8, and 15 every 4 weeks. Pharmacokinetics, safety, and efficacy were analyzed.
Results
Phase I: 17 patients received a dose‐escalating regimen of DHP107, 150–250 mg/m2 b.i.d. Dose‐limiting toxicities were neutropenia and febrile neutropenia. The MTD (recommended dose) for phase IIa was 200 mg/m2 b.i.d. Phase IIa: 11 patients with measurable advanced gastric cancer in whom first‐line therapy failed received DHP107 (MTD). Three confirmed partial responses were observed. Median progression‐free survival of gastric cancer patients (n = 16) treated at the MTD was 2.97 (95% confidence interval, 1.67–5.40) months (Fig. ). The most frequent grade 3/4 adverse events were neutropenia (35.3%) and leukopenia (17.6%) at the MTD (phase I and IIa combined; n = 17).
Conclusion
DHP107 showed good antitumor efficacy and was tolerable. The MTD (200 mg/m2 b.i.d.) is recommended for use in further studies comparing DHP107 with standard intravenous paclitaxel therapy.
经验总结
在理想情况下, 患者应能同时使用紫杉醇口服制剂和静脉注射制剂, 以便开发替代给药方案并规避聚氧乙烯蓖麻油（巴斯夫公司, 德国路德维希港, https://www.basf.com）的不良反应
DHP107是一种新型紫杉醇口服制剂, 对于胃癌患者而言是一种可耐受的可行治疗方案, 数据显示其疗效与紫杉醇静脉注射制剂相似。
摘要
背景. 本研究评价了新型紫杉醇口服制剂DHP107的最大耐受剂量（MTD）及其在晚期实体瘤患者中的疗效和安全性。
患者和方法. I期研究：多个队列中的晚期实体瘤患者（3‐6例/队列）接受剂量递增的DHP107给药。IIa期研究：可测量晚期胃癌患者在第1、8、15天接受DHP107 200mg/m2 b.i.d.给药, 每4周为一个周期。分析了药代动力学、安全性和疗效。
结果. I期：17例患者接受DHP107 150–250mg/m2 b.i.d.剂量递增方案。剂量限制性毒性为中性粒细胞减少症和发热性中性粒细胞减少症。IIa期研究的MTD（推荐剂量）为200mg/m2 b.i.d.。IIa期：11例一线治疗失败的可测量晚期胃癌患者接受DHP107（MTD）给药。观测到3例经证实的部分缓解。胃癌患者（16例）接受MTD治疗时的中位无进展生存期为2.97个月（95%置信区间：1.67‐5.40个月）（图1）。MTD下最常见的3/4级不良事件为中性粒细胞减少症（35.3%）和白细胞减少症（17.6%）（I期和IIa期合并；17例）。
结论. DHP107具有良好的抗肿瘤疗效且可耐受。建议在DHP107与静脉注射用紫杉醇标准治疗的进一步比较研究中采用MTD（200mg/m2 b.i.d.）。