A Phase I dose-escalation study of afatinib combined with nintedanib in patients with advanced solid tumors

被引：7

作者：

Gordon, Michael S. ^{[1
,2
]}

Springett, Gregory M. ^{[3
]}

Su, Yungpo Bernard ^{[4
]}

Ould-Kaci, Mahmoud ^{[5
]}

Wind, Sven ^{[6
]}

Zhao, Yihua ^{[7
]}

LoRusso, Patricia M. ^{[8
,9
]}

机构：

[1] Pinnacle Oncol Hematol, Scottsdale, AZ 85258 USA

[2] Pinnacle Oncol Hematol, Scottsdale, AZ 85258 USA

[3] Univ S Florida, H Lee Moffitt Canc Ctr, Expt Therapeut Program, Tampa, FL 33612 USA

[4] Nebraska Canc Specialists, Omaha, NE 68114 USA

[5] Boehringer Ingelheim GmbH & Co KG, F-75013 Paris, France

[6] Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany

[7] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA

[8] Wayne State Univ, Karmanos Canc Ctr, Detroit, MI 48201 USA

[9] Yale Canc Ctr, New Haven, CT 06520 USA

来源：

FUTURE ONCOLOGY | 2015年 / 11卷 / 10期

关键词：

afatinib; BIBF; 1120; BIBW; 2992; ErbB family blocker; nintedanib; pharmacokinetics; Phase I; triple angiokinase inhibitor; ERBB FAMILY BLOCKER; CELL LUNG-CANCER; BIBF; 1120; OPEN-LABEL; ANGIOKINASE INHIBITOR; KINASE INHIBITOR; TYROSINE KINASE; DUAL INHIBITOR; EGFR; PHARMACOKINETICS;

D O I：

10.2217/fon.15.50

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Aims: To evaluate the safety and maximum tolerated dose (MTD) of afatinib combined with nintedanib. Materials & methods: Patients received afatinib 10-20 mg daily plus nintedanib 150-200 mg twice daily (28-day cycle). Dose escalation followed a 3+3 design. Results: Patients received afatinib/nintedanib: 10/150 mg (n = 11); 10/200 mg (n = 13; MTD); 20/200 mg (n = 4). Four patients had dose-limiting toxicities (all grade 3): increased alanine aminotransferase (afatinib/nintedanib: 10/150 mg), diarrhea (10/200 mg), dehydration (20/200 mg), diarrhea with elevated liver enzymes (20/200 mg). Frequent treatment-related adverse events were diarrhea, nausea, anorexia, fatigue and vomiting. In total, 14 patients (46.2%) had objective responses at the MTD. Conclusion: The MTD, afatinib 10 mg daily plus nintedanib 200 mg twice daily, had a manageable safety profile, but was considered subtherapeutic for Phase II evaluation.

引用

页码：1479 / 1491

页数：13

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