Puquitinib mesylate, an inhibitor of phosphatidylinositol 3-kinase p110δ, for treating relapsed or refractory non-Hodgkin's lymphoma.
OBJECTIVE
To determine the safety of Puquitinib Mesylate (XC-302), an oral inhibitor of phosphatidylinositol 3-kinase, in treating relapsed or refractory non-Hodgkin's lymphoma (NHL).


METHODS
Between October 2013 and July 2015, 21 patients from Sun Yat-sen University Cancer Center were treated twice daily on each day of a 28-day cycle (median number of cycles, 2; maximum, 20) with XC-302 at a post prandial dose of 25 mg, 37.5 mg, or 50 mg. Adverse events (AEs), AUClast and Cmax, response rates, and overall survival were assessed.


RESULTS
Patients had received a median (range) of 1 (1 to 3) previous cancer treatments. At the latest follow-up, two patients were still benefitting from the study. The most common drug-related AEs were elevations in alanine transaminase (ALT, 14 of 21 patients) and aspartate transaminase (AST, 7 of 21 patients). Four patients, both in the-50-mg group, had dose-limiting toxicities, and therapy was discontinued in a fifth because of persistent abnormal liver function. The overall response rate was 2 of19. Serum concentrations of XC-302 increased in a dose-dependent pattern. Median progression-free survival in all patients was 1.9 (95% CI, 1.7 to 2.0) months.


CONCLUSIONS
XC-302 has an acceptable safety profile and offers potential therapeutic value to patients with relapsed or refractory non-Hodgkin lymphoma.
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.|Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Hang
H
Yang
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.|Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Yu
Y
Wang
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.|Clinical Trial Center, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Jing
J
Zhan
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.|Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Yi
Y
Xia
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.|Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Peng
P
Sun
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.|Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Xi-Wen
XW
Bi
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.|Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Pan-Pan
PP
Liu
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.|Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Zhi-Ming
ZM
Li
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.|Clinical Trial Center, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Su
S
Li
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.|Nursing Department, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Ben-Yan
BY
Zou
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.|Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Wen-Qi
WQ
Jiang
D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000328:Adult; D000368:Aged; D000634:Aminoquinolines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D000081082:Phosphoinositide-3 Kinase Inhibitors
D000634:Aminoquinolines; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; C000610523:puquitinib; D000225:Adenine
PI3K pathway; XC-302; non-Hodgkin lymphoma; pharmacokinetics; safety and efficacy