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Ma, B. B. Y.; Goh, B. C.; Lim, W. T.; Hui, E. P.; Tan, E. H.; Lopes, G. de Lima; Lo, K. W.; Li, L.; Loong, H.; Foster, N. R.; Erlichman, C.; King, A. D.; Kam, M. K. M.; Leung, S. F.; Chan, K. C.; Chan, A. T. C.
Investigational new drugs, 08/2015, Letnik: 33, Številka: 4Journal Article
Summary Background This study investigated the activity of MK-2206, an AKT inhibitor, in metastatic or recurrent nasopharyngeal carcinoma (NPC). Method Oral MK-2206 at a dose of 200 mg was administered on days 1, 8, 15 and 22 of a 28-day cycle until progression. Plasma EBV DNA clearance during the first month of treatment was measured, and archived tumors were analyzed for the expression of AKT and PIK3CA mutation and PIK3CA amplification. The dual primary endpoint was objective response rate and 6-month progression-free survival (PFS) rate. Results 21 patients were enrolled and one patient achieved a partial response (5 %) and 11 had stable disease (52 %), with a median PFS of 3.5 months (95 % confidence interval, CI: 0.9–7.3). The 6-month PFS rate was 43 % (95 % CI: 22–66 %) and the median OS was 10 months (95 % CI: 5.9 months–not reached). Seven patients (33 %) experienced grade 3 toxicities which could be related to MK-2206. Macular-papular rash was the most common ( n = 6), followed by hyperglycemia ( n = 2) and fatigue ( n = 1). In the 12 tumor samples analyzed, PIK3CA amplification was detected in one patient’s primary NPC, who had SD lasting over 12 months. Patients with decreasing EBV DNA values over time were more likely to be alive and progression-free for at least 6 months than those without a decrease ( p = 0.001). Conclusion The study was terminated due to the limited activity observed in this heavily pre-treated group of patients. Further studies are needed to elucidate the optimal way of selecting patients for AKT inhibitors.
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Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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