Drug-drug interactions in patients using tyrosine kinase inhibitors: A multicenter retrospective study.

PURPOSE: Tyrosine kinase inhibitors (TKIs) are frequently used drugs in oncology practice. Although oral administration is an advantage, long-term use increases potential drug-drug interaction risk. The purpose of this study was to assess the prevalence of potential TKI-drug interaction (PTDI) in patients who used TKIs and increase awareness of this subject. METHODS: We retrospectively evaluated the data of 310 patients collected from four different oncology centers, where TKIs were administered for solid organ cancer, between January 2007 and December 2017. The potential interaction between TKI and any other prescribed drug was determined using ''Lexicomp® Drug Interactions, App Version 1.1'' software. RESULTS: Overall, 310 patients were included; among those, 301 (97.1%) were using another drug with TKI and 147 (47.4%) experienced PTDI at least once. The median number of additional drugs was 4 (range 1-12). We detected 250 PTDIs, of which 30.8% were major interactions. The most frequently interacting TKI was imatinib (29.6%), and the additional drug group was antibiotics (21.2%). We observed that PTDIs caused the following effects: TKI concentration was increased or decreased owing to 14.4% or 22.8% PTDIs, respectively, and electrocardiographic QT prolongation occurred in 22% of all PTDIs. Multivariate analysis demonstrated that use of higher number of additional drugs (odds ratio/OR=1.63), pre-existing lung cancer (OR=8.82), and use of pazopanib (OR=9.22) were potential risk factors. CONCLUSION: The rate of PTDI is quite high in patients using TKIs. Effort must be made to increase awareness of this subject. Increasing awareness aids in lowering toxicity rates and providing efficient antitumor therapy.

A Modified Epirubicin and Oxaliplatin Plus Capecitabine (EOX) Regimen as a Second- Line Therapy in Patients with Advanced Gastric Cancer

Objective: We aimed to evaluate the effectiveness of an mEOX (modified epirubicin, oxaliplatin plus capecitabine) regimen as second line therapy after failure of mDCF (modified docetaxel, cisplatin plus fluorouracil). Methods: Gastic cancer patients for whom first-line therapy was unsuccessful and who subsequently received mEOX (epirubicin 50 mg/ m2 on day 1, oxaliplatin 85 mg/m² day 1 and capecitabine twice-daily dose of 625 mg/ m2, p.o. for 2 weeks) every 3 weeks until disease progression or unacceptable toxicity, were retrospectively analyzed. Results: The study population comprised 129 cases with a median age of 55 years (range= 27-78), the majority being male (76 %). Most (75.2%) had ≥ 2 sites of metastasis. The median number of chemotherapy courses was five (range= 2­9). Forty-nine achieved a partial response and 33 showed stable disease, resulting in a ORR (overall response rate) of 38% and a DCR (disease control rate) of 63.6%. The most frequent features of grade 3-4 hematological and non-hematological toxicity were neutropenia (8.5%) and nausea/vomiting (5.4%). None of the patients suffered death due to toxicity. The median PFS was 4.7 months (95% CI, 4.1­5.3) and the OS was 7.4 months (95% CI, 6.3­8.5). On multivariate analysis, age ≥ 60 years and ECOG performance status (0-1) were independent prognostic factors affecting PFS and OS. Conslusions: In advanced gastric cancer patients, who progress after first line chemotherapy and have an ECOG performance status of 0-1, mEOX is a well tolerated triple regimen associated with a promising OS and PFS.

Clinicopathological and prognostic characteristics in patients with AFP-secreting gastric carcinoma.

The aim of the present study was to determine whether there are any clinicopathological or prognostic differences between patients with α-fetoprotein-secreting gastric carcinoma (AFP-SGC) and non-AFP-SGC. Pathological parameters, clinical parameters, and treatment efficacy were compared in patients with AFP-SGC and non-AFP-SGC. In total, 362 patients (53 with AFP-SGC and 309 with non-AFP-SGC) were included in the present study. Patients with AFP-SGC had significantly higher levels of lymphovascular invasion, perineural invasion (PNI), rate of liver metastasis, and stage IV cancer compared with patients with non-AFP-SGC (P<0.05). The median overall survival (OS) rate was 12.6 months in the AFP-SGC group, and 22.1 months in the non-AFP-SGC group (P<0.001). The median OS and disease free survival (DFS) of patients with stage I-III AFP-SGC were 28.1 and 13.4 months, respectively, whereas for patients with non-AFP-SGC, the OS and DFS were 45.3 and 38.0 months, respectively (P=0.01; P=0.02). The median OS for the stage IV AFP-SGC and non-AFP-SGC groups was 9.3 and 11.5 months, respectively (P=0.14). Multivariate analysis of the entire patient group revealed that the Eastern Cooperative Oncology Group (ECOG) performance score of ≥2, lymph node involvement, presence of PNI, high levels of carcinoembryonic antigen, and distant metastasis were significantly correlated with OS. The lymph node involvement, ECOG performance score of ≥2, AFP-SGC type, and weight loss at diagnosis were also significant factors influencing the DFS in the stage I-III group. In conclusion, patients with AFP-SGC had more aggressive clinicopathological features and biological behavior with an increased tendency of liver metastasis compared with patients with non-AFP-SGC. In the near future, AFP may become an important surrogate marker to manage therapies of patients with gastric cancer.