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.

Is the Charlson Comorbidity Index a Prognostic Indicator for Toxicity and Mortality in Elderly Patients with Locally Advanced Rectal Cancer?

BACKGROUND: Aging is significantly related to multiple comorbidities. Even with a good performance score, some elderly patients may have poor survival outcomes. We aimed to evaluate the prognostic value of the Charlson comorbidity index (CCI) for mortality and toxicity in elderly patients with locally advanced rectal cancer (LARC). METHODS: Seventy-two elderly patients with LARC who were treated with neoadjuvant chemoradiotherapy (CRT) were included. Based on their CCI score, severity of the comorbidity was categorized into 2 groups: CCI<7 and CCI≥7. RESULTS: The overall survival (OS) at 5 years was 54.4 percent in patients treated with neoadjuvant CRT. Median OS was not reached for all patients as well as patients with CCI score <7, but median OS was 25 (95% CI 1.0-62.1) months in patients with CCI≥7 (P=0.002). The OS at 2 years was 79.1 percent in the patients with CCI <7 and 50.0 percent in the patients with CCI score ≥7 (P=0.002). Moreover, there was a trend toward, patients with higher CCI score who had more treatment related to grade 3 or 4 toxicity compared to those with CCI score <7 (33.3% vs 13.3%, respectively, P=0.09). Multivariable analysis indicated that the CCI score ≥7, presence of down-staging after therapy and clinical stage (III) independently predict mortality (HR 6.14, 95%CI 2.45-15.35, P<0.001) in patients with LARC. CONCLUSION: Although CCI score was not significantly associated with both toxicity and disease-free survival (DFS), we suggest that baseline CCI score might be a valuable prognostic indicator for physicians to evaluate elderly patiens with LARC for optimal treatment.

Evaluation of prognostic factors and treatment in advanced small bowel adenocarcinoma: report of a multi-institutional experience of Anatolian Society of Medical Oncology (ASMO).

PURPOSE: Small bowel adenocarcinoma (SBA) is a rare tumor of the gastrointestinal system with poor prognosis. Since these are rarely encountered tumors, there are limited numbers of studies investigating systemic treatment in advanced SBA. The purpose of this study was to evaluate the prognostic factors and systemic treatments in patients with advance SBA. METHODS: Seventy-one patients from 18 Centers with advanced SBA were included in the study. Fifty-six patients received one of the four different chemotherapy regimens as first-line therapy and 15 patients were treated with best supportive care (BSC). RESULTS: Of the 71 patients, 42 (59%) were male and 29 (41%) female with a median age of 56 years. Median follow- up duration was 14.3 months. The median progression free survival (PFS) and overall survival (OS) were 7 and 13 months, respectively (N=71). In patients treated with FOLFOX (N=18), FOLFIRI (N=11), cisplatin-5-fluorouracil/ 5-FU (N=17) and gemcitabine alone (N=10), median PFS was 7, 8, 8 and 5 months, respectively, while median OS was 15, 16, 15 and 11 months, respectively. No significant differences between chemotherapy groups were noticed in terms of PFS and OS. Univariate analysis revealed that chemotherapy administration, de novo metastatic disease, ECOG PS 0 and 1, and overall response to therapy were significantly related to improved outcome. Only overall response to treatment was found to be significantly prognostic in multivariate analysis (p=0.001). CONCLUSIONS: In this study, overall response to chemotherapy emerged as the single significant prognostic factor for advanced SBAs. Platin and irinotecan based regimens achieved similar survival outcomes in advanced SBA patients.

Prognostic factors for recurrence-free survival in patients with HER2-positive early-stage breast cancer treated with adjuvant trastuzumab.

BACKGROUND: The objective of this study was to identify prognostic factors affecting the recurrence-free survival (RFS) in patients who received a 52-week trastuzumab therapy for HER2-positive early stage breast cancer (EBC). PATIENTS AND METHODS: The medical records of all patients with EBC from 10 centers were analyzed. Pathologic and clinical tumor characteristics were evaluated in 424 female patients who received 52 weeks of adjuvant trastuzumab for HER2-positive EBC. Survival was estimated using the Kaplan-Meier method. Univariate analyses of RFS were performed with the log-rank test. Independent prognostic and predictive factors affecting RFS were assessed by Cox regression analysis. RESULTS: Median follow-up time was 33.1 months (range 9.2-75.9 months). 3-year RFS and overall survival were 87 and 97%, respectively. In multivariate analysis, patients aged 70 years or over (p = 0.017, relative risk (RR) 2.7, 95% confidence interval (CI) 1.19-6.13), patients with > 9 positive lymph nodes (p = 0.001, RR 2.52, 95% CI 1.42-4.46), and those with progesterone receptor-negative tumors (p = 0.006, RR 2.33, 95% CI 1.27-4.27) had worse RFS. CONCLUSION: In spite of a 52-week adjuvant trastuzumab treatment, classic poor prognostic factors for invasive EBC remained as such in patients with HER2-positive EBC.