Phase I/II study of bevacizumab with BKM120, an oral PI3K inhibitor, in patients with refractory solid tumors (phase I) and relapsed/refractory glioblastoma (phase II)
| Autor: | Kevin P. Becker, John D. Hainsworth, Tarek Mekhail, David Wright, Howard A. Burris, Sajeel A. Chowdhary, Janice Faulkner Eakle, Kimberly West-Osterfield, Gilbert Darin Anthony Padula, Mythili Shastry, Meredith Scarberry, Kent C. Shih, Robert M. Langdon, Candice A. Shaifer, Kathleen Yost |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Maximum Tolerated Dose Bevacizumab Morpholines Aminopyridines Gastroenterology Phosphatidylinositol 3-Kinases 03 medical and health sciences 0302 clinical medicine Refractory Neoplasms Internal medicine Antineoplastic Combined Chemotherapy Protocols Humans Medicine In patient PI3K/AKT/mTOR pathway Aged Aged 80 and over Salvage Therapy business.industry Middle Aged Prognosis medicine.disease Survival Rate Regimen Phase i ii Neurology Oncology Drug Resistance Neoplasm 030220 oncology & carcinogenesis Relapsed refractory Female Neurology (clinical) Neoplasm Recurrence Local Glioblastoma business 030217 neurology & neurosurgery Follow-Up Studies medicine.drug |
| Zdroj: | Journal of Neuro-Oncology. 144:303-311 |
| ISSN: | 1573-7373 0167-594X |
| DOI: | 10.1007/s11060-019-03227-7 |
| Popis: | Current bevacizumab-based regimens have failed to improve survival in patients with recurrent glioblastoma. To improve treatment efficacy, we evaluated bevacizumab + BKM120, an oral pan-class I PI3K inhibitor, in this patient population. A brief phase I study established the optimal BKM120 dose to administer with standard-dose bevacizumab. BKM120 60 mg PO daily + bevacizumab 10 mg/kg IV every 2 weeks in 28-day cycles was then administered to patients with relapsed/refractory glioblastoma in the phase II portion. Eighty-eight patients enrolled (phase I, 12; phase II, 76). In phase I, BKM120 80 mg PO daily produced dose limiting toxicity in 3 of 6 patients; a BKM120 dose of 60 mg PO daily was established as the maximum tolerated dose. In phase II, the median progression-free survival (PFS) was 4.0 months (95% CI 3.4, 5.4), PFS at 6 months was 36.5%, and the overall response rate was 26%. Forty-two patients (57%) experienced one or more serious treatment related toxicities. The most common CNS toxicities included mood alteration (17%) and confusion (12%); however, these were often difficult to classify as treatment- versus tumor-related. The efficacy seen in this study is similar to the efficacy previously reported with single-agent bevacizumab. This regimen was poorly tolerated, despite the low daily dose of BKM120. Further development of this combination for the treatment of glioblastoma is not recommended. |
| Databáze: | OpenAIRE |
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