Anti-Epidermal Growth Factor Receptor (EGFR) Treatment in Patients with Metastatic Colorectal Cancer

Colorectal cancer is one of the most common cancer types and still a major public health problem. Approximately a half of the patients develop metastasis during the course of disease. Prognosis of metastatic colorectal cancer (mCRC) is poor with best supportive care alone (median survival: 6 months). Fortunately, combination chemotherapy has significantly improved survival up to 17–22 months. Cetuximab and panitumumab, the two monoclonal antibodies (mAbs) against epidermal growth factor receptor (EGFR), provide significant clinical benefit in only RAS wild (WT) mCRC. Major side effects are skin toxicity, infusion reactions, fatigue, and electrolyte imbalances. When these mAbs are combined with chemotherapy, overall survival could be as long as 24 months. However, RAS WT status does not ensure response to anti-EGFR mAbs. In addition, RAS WT patients consequently develop resistance to these agents after an initial responsive period. Therefore, understanding the primary and secondary resistance mechanisms apart from RAS status is very important to improve outcomes of mCRC patients. Oncogenic activation of EGFR downstream signaling effectors (KRAS, BRAF, PTEN, and PIK3CA) appears to be the main components of resistance. In future, a comprehensive biomarker analysis will probably help to identify the mCRC patients who will truly benefit from anti-EGFR mAbs

Effect of carvedilol on silent anthracycline-induced cardiotoxicity assessed by strain imaging: A prospective randomized controlled study with six-month follow-up

Background: The use of antracycline (ANT) in breast cancer has been associated with adverse cardiac events. Two-dimensional (2D) strain imaging (SI) can provide a more sensitive measure of altered left ventricular (LV) systolic function. We aimed to evaluate the preventive effect of carvedilol administration assessed by SI in a patient with breast cancer treated with ANT.Methods: Patients receiving ANT were randomly assigned to the carvedilol- or placebo-receiving group. Each received an echocardiographic examination with conventional 2D echocardiography, pulsed tissue Doppler, and 2D SI prior to and 6 months post ANT treatment.Results: During the 6-month follow-up period there were no patient deaths or interrupted chemotherapy treatments due to doxorubicin-induced cardiotoxicity. Both left ventricular ejection fraction (LVEF) and fractional shortening (FS) were within normal limits for all patients before and after ANT therapy. EF, FS and LV dimensions were measured using M-mode echocardiography and found to be similar in both groups before and after ANT therapy. The mean EF, FS, and LV echocardiograph baseline and control dimensions were similar in both groups after 6 months. Though baseline SI parameters were similar between the groups, there was a significant decrease in LV basal septal and basal lateral peak systolic strain in the control group compared to the carvedilol group.Conclusions: These results indicate that carvedilol has a protective effect against the cardiotoxicity induced by ANT.

Serum vascular cell adhesion molecule-1 (VCAM1) level is elevated in colorectal cancer regardless of the tumor stage

Purpose: Vascular cell adhesion molecule-1 (VCAM1) is a transmembrane glycoprotein, which is expressed on endothelium and plays role in inflammation. It is over-expressed on colorectal cancer (CRC) cells and plays role in metastasis development and angiogenesis. We aimed to compare serum VCAM1 levels of CRC patients with heathy controls and evaluate its relationship with clinicopathological parameters, treatment response and overall survival (OS).Methods: The study enrolled 111 patients with histopathologically confirmed CRC followed-up in our clinic and 30 sex- and age-matched healthy controls. Pre-treatment serum VCAM1 levels were determined by the solid-phase sandwich ELISA method.Results: Metastatic disease was present in 57 patients. Forty percent of 40 metastatic patients receiving systemic therapy had partial or complete response. The median serum VCAM1 level was significantly higher in CRC patients than controls (p<0.001). In addition, serum VCAM1 level was significantly higher in diabetic CRC patients than those without diabetes (p = 0.03). There was no significant relationship between VCAM1 and other clinicopathological parameters including stage and response to systemic therapy. The median follow-up period was 12 (±8.2) months. Twenty patients were dead at the time of analysis. The presence of metastasis (p < 0.001) and elevated CEA level (p < 0.001) were factors affecting OS significantly. However, serum VCAM1 did not have a significant impact on OS (p = 0.55).Conclusion: Serum VCAM1 level is significantly elevated in CRC patients regardless of the tumor stage. However, it has no prognostic or predictive role for response to systemic therapy

Combination of Capecitabine and Phenytoin May Cause Phenytoin Intoxication: A Case Report

Capecitabine is an oral antineoplastic agent, and phenytoin is an anticonvulsant drug with a narrow therapeutic index. Although the interaction between capecitabine and phenytoin is rare, it may be potentially fatal. This interaction is thought to be at the level of CYP2C9 isoenzyme system in the liver. Here, we present a patient with metastatic breast cancer who developed phenytoin intoxication when using capecitabine and phenytoin together. Closely monitoring plasma phenytoin levels is essential if capecitabine is used with phenytoin concurrently

Renin-Angiotensin System Blockers May Prolong Survival of Metastatic Non-Small Cell Lung Cancer Patients Receiving Erlotinib

The aim of this study is to determine whether renin-angiotensin system blockers (RASBs), which include angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-2 receptor 1 blockers (ARBs), improve the overall survival (OS) of patients with metastatic non-small cell lung cancer (NSCLC).The medical charts of 117 patients with metastatic NSCLC were retrospectively assessed. Thirty-seven patients (RASB group) using RASBs during systemic treatment were compared with 80 controls (control group) who did not use RASBs following the diagnosis of NSCLC. The histological tumor subtype, performance status, age, sex, smoking status, comorbidities, other medications, chemotherapeutics (CT), and erlotinib that were received in any line of treatment were recorded. We compared the OS of the patients in the RASB and control groups.The median (SD) age of the patients was 61 (+/- 1) years and all patients were administered systemic treatment (CT or erlotinib). The patients in RASB group were more likely to be smokers, have hypertension and ischemic heart disease, and use erlotinib, thiazides, beta-blockers, and calcium-channel blockers (P<0.05 for all) compared with the control group. The median follow-up time was 18.9 months (range 1-102 months) for the entire group. The median follow-up period was longer for RASB group than control group (17 vs 11 months, P=0.033). The most commonly prescribed RASB agent was valsartan (n=12/37). At the time of the analysis, 98 (83.7%) of all patients had died. In the univariate analysis, the median OS was longer in the RASB group compared with the control group (17 [+/- 4.1] vs 12 [+/- 1.4] months, P=0.016). Interestingly, further analyses revealed that RASBs significantly improved OS only if used with erlotinib concurrently (34 [+/- 13.8] vs 25 [+/- 5] months, P=0.002) and the OS benefit was more attributable to ARBs because only 4 patients received ACEI and erlotinib concurrently. However, the benefit of ARBs on OS disappeared in the multivariate analysis.The use of ARBs during erlotinib treatment may prolong OS of patients with metastatic NSCLC

Age is a prognostic factor affecting survival in lung cancer patients

Despite all efforts at management, prognosis of advanced lung cancer is extremely poor, with a median survival time of similar to 1 year. The number of cancer patients aged >70 years is significantly increased among the cancer patient population. The aim of this study was to investigate the clinical importance of age in lung cancer. Data from 110 patients with histologically confirmed lung cancer, who were treated and followed up in the Institute of Oncology, University of Istanbul, were recorded from medical charts. There were 100 (91%) males with a median age of 59 years (range, 35-88 years). The majority of patients had non-small cell lung cancer (NSCLC; 84%) and metastatic stage (56%). The rate of positive response to chemotherapy was lower in elderly patients (P=0.01) and the incidence of anemia was higher compared with that in younger patients (P=0.02). The majority of mortalities occurred in elderly patients (P=0.01). The median survival time of elderly patients was significantly lower compared with that of younger patients (37.8 vs. 57 weeks; P=0.009). The 1-year survival rates in younger and elderly patients were 67.3 and 42.5%, respectively. In multivariate analysis, elderly patients also had significantly poorer survival (P=0.023). In the group of elderly patients, analyses revealed that significant prognostic factors, including stage of disease and serum lactate dehydrogenase (LDH) levels, were associated with survival. Elderly patients diagnosed with small cell lung cancer had a poorer outcome compared with those with NSCLC (P=0.009), and older patients with elevated serum LDH levels had a shorter survival time compared with those with normal levels (P=0.042). In conclusion, age is one of the major prognostic factors affecting survival in lung cancer patients; therefore, patients should be managed according to age in clinical practice

Effect of Astragalus Membranaceus on Patients with Metastatic Non-Small Cell Lung Cancer: A Retrospective Cohort Study

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Does Beta-blocker Therapy Improve the Survival of Patients with Metastatic Non-small Cell Lung Cancer?

Aim: To determine whether beta-blockers (BBs) improve the overall survival (OS) of patients with metastatic non-small cell lung cancer (NSCLC). Materials and Methods: The medical charts of 107 patients with metastatic NSCLC were retrospectively assessed. Thirty-five patients (BB group) using BBs during chemotherapy (CT) were compared with 72 controls [control=(C) group] who did not use BBs following the diagnosis of NSCLC. The histological tumor subtype, performance status (ECOG), age, gender, smoking status, comorbidities, other medications and chemotherapeutics that were received in any line of treatment were recorded. We compared the overall survival (OS) of the patients in the BB and C groups. Results: The mean age of the patients was 61 years (range 42-81 years) and all patients were administered CT. The BB group was more likely to have HT and IHD and was more likely to use RAS blockers (p<0.01 for all) compared with the C group, as expected. The mean follow-up time was 17.8 months (range 1-102 months) for the entire group. The most commonly prescribed BB agent was metoprolol (80% of cases). At the time of the analysis, 74 (69%) of all patients had died. In the univariate analysis the median overall survival (OS) was 19.25 (+/- 2.87) months (95% CI: 13.62-24.88) in the BB group and 13.20 (+/- 2.37) months (95% CI: 8.55-17.85) in the C group (p=0.017). However, the benefit of BBs on survival disappeared in the multivariate analysis. Conclusions: The use of BBs during CT may be associated with an improved OS for patients with metastatic NSCLC