Chinese guidelines recommend POF (paclitaxel, oxaliplatin, and 5‐FU/levoleucovorin) as first‐line treatment for advanced gastric cancer (AGC). Apatinib can augment the antitumor effect of paclitaxel, oxaliplatin, or fluorouracil in preclinical studies of AGC. A phase I clinical trial was conducted to evaluate the anticancer activity and maximum tolerated dose (MTD) of apatinib plus POF in treatment‐naïve patients with AGC and to establish a recommended phase II dose. Participants received escalating doses of daily oral apatinib (250, 375, 500, 625, 750, and 850 mg) plus POF every 2 weeks using a conventional “3 + 3” study design. Among 21 treated patients, one experienced a dose‐limiting toxicity (grade 3 skin ulceration at 850 mg). No MTD was reached. Apatinib 750 mg plus POF was recommended for phase II study. The most common grade 3–4 adverse events (AEs) were neutropenia (33.3%), mucositis (14.3%), and hand‐foot syndrome (14.3%). Median progression‐free and overall survival were 10.4 months (95% CI: 6.3, 14.6) and 18.4 months (95% CI: 9.8, 28.2), respectively. Apatinib up to 850 mg coadministered with POF was well tolerated with manageable AEs. The safety and anticancer activity of this regimen warrants its further investigation as first‐line treatment for AGC in a larger study.
1 October 2020 in Translational Lung Cancer Research
Lung cancer is the leading cause of cancer-related mortality worldwide. Patients with locally advanced non-small cell lung cancer (NSCLC) have lower overall survival. Studies have shown that some patients with unresectable stage III NSCLC develop disease progression after initial chemoradiotherapy, and new treatment is needed to improve the prognosis of these patients. The rapid development of therapy has greatly changed and continued to renew the treatment strategy of advanced NSCLC. However, the clinical treatment for patients with the wild-type gene remains problematic, and chemotherapy with platinum are not yet considered satisfactory. Herein, we are reporting a case of a patient with wild-type gene mutation locally advanced NSCLC who was treated with neoadjuvant therapy by using combined targeted anti-PD-1 immunotherapy and chemotherapy. The percentage of tumor cells with membranous PD-L1 staining (tumor proportion score) was 90% or greater. After receiving all three cycles of treatment, the patient underwent video-assisted right upper lung lobectomy and wedge resection plus radical mediastinal lymph node dissection. Pathological section samples showed a pathological complete response. This experience has led us to believe that the subgroup of patients with unresectable advanced NSCLC may benefit from this strategy and may have an opportunity for radical surgery.
1 January 2024 in American Journal of Cancer Research
Non-SMC condensing I complex subunit G (NCAPG) has been implicated in tumor progression. However, its role, potential mechanism and prognostic significance in human non-small cell lung cancer (NSCLC) remain elusive. Through the conjoint analysis of the TCGA and The Gene Expression Omnibus (GEO) databases, we confirmed that NCAPG is an upregulated gene. The prognostic value of NCAPG was elucidated through data analysis. The functional roles and mechanistic insights of NCAPG in NSCLC growth and metastasis were evaluated in vitro and in vivo. NCAPG expression was significantly increased in NSCLC. Multivariate Cox regression analysis demonstrated that NCAPG was an independent prognostic factor in patients with NSCLC. The high expression of NCAPG was significantly correlated with lymphatic metastasis. Additionally, the high expression of NCAPG effectively promoted the growth and metastasis of NSCLC in vitro and in vivo. In terms of mechanism, the interaction between NCAPG and Cyclin-dependent kinase 1 (CDK1) promotes the phosphorylation of Extracellular signal-regulated kinase (ERK). Overall, our results reveal the key role of NCAPG in NSCLC and highlight the regulatory function of the NCAPG/CDK1/ERK axis in regulating the progression of NSCLC, providing potential prognosis and therapeutic targets for the treatment of NSCLC.