A phase I/II study of poziotinib combined with paclitaxel and trastuzumab in patients with HER2-positive advanced gastric cancer
| Autor: | Jin Soo Kim, Jae Yong Cho, Na Mi Lee, Yung-Jue Bang, Dae Young Zang, Tae Yong Kim, Yeul Hong Kim, Eun Kee Song, Hye Sook Han, Se Hoon Park, Keun Wook Lee, Young Iee Park, Soo A. Jung, Sun Young Rha, Kyung Hun Lee |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Maximum Tolerated Dose Paclitaxel Receptor ErbB-2 medicine.medical_treatment Neutropenia Gastroenterology Loading dose Disease-Free Survival 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Stomach Neoplasms Trastuzumab Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Prospective Studies Adverse effect Aged Chemotherapy Dose-Response Relationship Drug business.industry General Medicine Middle Aged medicine.disease Rash COVID-19 Drug Treatment Survival Rate Oncology chemistry 030220 oncology & carcinogenesis Toxicity Quinazolines Female 030211 gastroenterology & hepatology medicine.symptom Coronavirus Infections business medicine.drug |
| Zdroj: | Gastric Cancer. 22:1206-1214 |
| ISSN: | 1436-3305 1436-3291 |
| DOI: | 10.1007/s10120-019-00958-4 |
| Popis: | Background Poziotinib (HM781-36B) is an irreversible pan-HER tyrosine kinase inhibitor which targets EGFR, HER2, and HER4. This prospective, multicenter, open-label, phase I/II study determined the maximum tolerated dose (MTD) and evaluated the safety and efficacy of poziotinib combined with paclitaxel and trastuzumab in patients with HER2-positive advanced gastric cancer (GC). Methods Patients with HER2-positive GC previously treated with one line of chemotherapy received oral poziotinib (8 mg or 12 mg) once daily for 14 days, followed by 7 days off. Paclitaxel (175 mg/m2 infusion) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg infusion) were administered concomitantly with poziotinib on day 1 every 3 weeks. Results In the phase I part, 12 patients were enrolled (7 at dose level 1, 5 at dose level 2). One patient receiving poziotinib 8 mg and 2 receiving poziotinib 12 mg had dose-limiting toxicities (DLTs); all DLTs were grade 4 neutropenia, one with fever. The most common poziotinib-related adverse events were diarrhea, rash, stomatitis, pruritus and loss of appetite. The MTD of poziotinib was determined to be 8 mg/day and this was used in the phase II part which enrolled 32 patients. Two patients (6.3%) had complete responses and 5 (15.6%) had partial responses (objective response rate 21.9%). Median progression-free survival and overall survival were 13.0 weeks (95% CI 9.8-21.9) and 29.5 weeks (95% CI 17.9-59.2), respectively. Conclusions The MTD of poziotinib combined with paclitaxel and trastuzumab was 8 mg/day. This combination yielded promising anti-tumor efficacy with manageable toxicity in previously treated patients with HER2-positive GC. |
| Databáze: | OpenAIRE |
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