Impact of concurrent medications on clinical outcomes of cancer patients treated with immune checkpoint inhibitors: analysis of Health Insurance Review and Assessment data.

PURPOSE: Medications regulating immune homeostasis and gut microbiota could affect the efficacy of immune checkpoint inhibitors (ICIs). This study aimed to investigate the impact of concurrent medications on the clinical outcomes of patients with cancer receiving ICI therapy in South Korea. METHODS: We identified patients newly treated with ICI for non-small cell lung cancer (NSCLC), urothelial carcinoma (UC), and malignant melanoma (MM) between August 2017 and June 2020 from a nationwide database in Korea. The effect of concurrent antibiotics (ATBs), corticosteroids (CSs), proton-pump inhibitors (PPIs), and opioids prescribed within 30 days before ICI initiation on the treatment duration and survival was assessed. RESULTS: In all, 8870 patients were included in the ICI cohort (NSCLC, 7,128; UC, 960; MM, 782). The patients were prescribed ATBs (33.8%), CSs (47.8%), PPIs (28.5%), and opioids (53.1%) at the baseline. The median overall survival durations were 11.1, 12.2, and 22.1 months in NSCLC, UC, and MM subgroups, respectively, since starting the ICI mostly as second-line (NSCLC and UC) and first-line (MM) therapy. Early progression was observed in 34.2% of the patients. Opioids and CS were strongly associated with poor survival across all cancer types. A high number of concurrent medications was associated with early progression and short survival. Opioid and CS use was associated with poor prognosis in all patients treated with ICIs. However, ATBs and PPIs had a cancer-specific effect on survival. CONCLUSION: A high number of concurrent medications was associated with poor clinical outcomes.

Impacts of Subtype on Clinical Feature and Outcome of Male Breast Cancer: Multicenter Study in Korea (KCSG BR16-09).

PURPOSE: The treatment of male breast cancer (MBC) has been extrapolated from female breast cancer (FBC) because of its rarity despite their different clinicopathologic characteristics. We aimed to investigate the distribution of intrinsic subtypes based on immunohistochemistry, their clinical impact, and treatment pattern in clinical practice through a multicenter study in Korea. MATERIALS AND METHODS: We retrospectively analyzed clinical data of 248 MBC patients from 18 institutions across the country from January 1995 to July 2016. RESULTS: The median age of MBC patients was 63 years (range, 25 to 102 years). Among 148 intrinsic subtype classified patients, 61 (41.2%), 44 (29.7%), 29 (19.5%), and 14 (9.5%) were luminal A, luminal B, human epidermal growth factor receptor 2, and triple-negative breast cancer, respectively. Luminal A subtype showed trends for superior survival compared to other subtypes. Most hormone receptor-positive patients (166 patients, 82.6%) received adjuvant endocrine treatment. Five-year completion of adjuvant endocrine treatment was associated with superior disease-free survival (DFS) in patients classified with an intrinsic subtype (hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.04 to 0.49; p=0.002) and in all patients (HR, 0.16; 95% CI, 0.05 to 0.54; p=0.003). CONCLUSION: Distribution of subtypes of MBC was similar to FBC and luminal type A was most common. Overall survival tended to be improved for luminal A subtype, although there was no statistical significance. Completion of adjuvant endocrine treatment was associated with prolonged DFS in intrinsic subtype classified patients. MBC patients tended to receive less treatment. MBC patients should receive standard treatment according to guidelines as FBC patients.

COMPrehensive geriatric AsseSSment and multidisciplinary team intervention for hospitalised older adults (COMPASS): a protocol of pragmatic trials within a cohort.

INTRODUCTION: There is an increased demand for services for hospitalised older patients with acute medical conditions due to rapidly ageing population. The COMPrehensive geriatric AsseSSment and multidisciplinary team intervention for hospitalised older adults (COMPASS) study will test the effectiveness of comprehensive geriatric assessment (CGA) and multidisciplinary intervention by comparing it with conventional care among acute hospitalised older adults in Korea. METHODS AND ANALYSIS: A multicentre trial within a cohort comprising three substudies (randomised controlled trials) will be conducted. The intervention includes CGA and CGA-based multidisciplinary interventions by physicians (geriatricians, oncologists), nurses, nutritionists and pharmacists. The multidisciplinary intervention includes nutritional support, medication review and adjustment, rehabilitation, early discharge planning and prevention of geriatric syndromes (falls, delirium, pressure sore and urinary retention). The analysis will be based on an intention-to-treat principle. The primary outcome is living at home 3 months after discharge. In addition to assessing the economic effects of the intervention, a cost-utility analysis will be conducted. ETHICS AND DISSEMINATION: The study protocol was reviewed and approved by the ethics committees of Seoul National University Bundang Hospital and each study site. The study findings will be published in peer-reviewed journals. Subgroup and further in-depth analyses will subsequently be published. TRIAL REGISTRATION NUMBER: KCT0006270.

Incidence and risk factors of hypertension therapy in Australian cancer patients treated with vascular signalling pathway inhibitors.

BACKGROUND: Clinical trials report systemic hypertension is an adverse effect of vascular signalling pathway inhibitor (VSPi) use. There are limited data from routine clinical practice. We aimed to estimate the real-world incidence and risk factors of new-onset and aggravated hypertension for cancer patients dispensed VSPi in whole-of-population Australian setting. METHODS: We used dispensing records for a 10% random sample of Australians to identify treatment with subsidised VSPi from 2013 to 2018. We further identified dispensings of oral antihypertensive medicines 6 months before and 12 months after VSPi therapy. We defined (i) new-onset hypertension in people first dispensed antihypertensives after VSPi and (ii) aggravated hypertension in people with prior antihypertensive use dispensed an additional, or higher strength, antihypertensive after VSPi. We applied the Fine-Gray cumulative incidence function and Cox proportional hazard regression. RESULTS: 1802 patients were dispensed at least one VSPi. The mean age of the cohort was 65 years and 57% were male. The incidence of new-onset treated hypertension was 24.3% (95%CI: 21.2-27.8); age ≥ 60 years (HR 1.74; 95%CI: 1.32-2.31) and treatment with oral tyrosine kinase inhibitors compared to bevacizumab (HR 1.96; 95%CI: 1.16-3.31) were risk factors. The incidence of aggravated hypertension was 25.2% (95%CI: 22.0-28.7) and risk was elevated for patients with renal cancer (HR 2.84; 95%CI: 1.49-5.41) and cancers other than colorectal (HR 1.85; 95%CI: 1.12-3.03). CONCLUSIONS: Our real-world estimates of incident hypertension appear comparable to those observed in clinical trials (21.6-23.6%). Our population-based study provides some insight into the burden of hypertension in patients commencing VSPi in routine practice.

Survival outcomes of patients with nonsmall cell lung cancer concomitantly receiving proton pump inhibitors and immune checkpoint inhibitors.

Recent evidence suggests that gut microbiota dysbiosis adversely affects the efficacy of immune checkpoint inhibitors (ICIs). Our objective was to investigate the association between concomitant use of proton pump inhibitors (PPIs) and ICIs, and poor prognosis in patients with nonsmall cell lung cancer (NSCLC). We conducted a cohort study using a completely enumerated lung cancer cohort from a nationwide healthcare database in South Korea. We identified 2963 patients treated with ICIs as second-line or later therapy for stage ≥IIIB NSCLC. PPI use was ascertained within 30-days before and on the date of ICI initiation, and nonuse was defined as no prescription of PPIs during this period. Using national vital statistics in South Korea, we assessed the risk of all-cause mortality associated with concomitant PPI use through a propensity score-matched Cox proportional hazard model. Among 1646 patients included after 1:1 propensity score-matching, concomitant PPI use was associated with a 28% increased risk of all-cause mortality, compared to nonuse (adjusted hazard ratio [HR] 1.28; 95% confidence intervals [CIs], 1.13-1.46). We observed an increased risk when we restricted the analysis to new users of PPI (adjusted HR = 1.64; 95% CI = 1.25-2.17). Subgroup analysis showed that PPI use was associated with high mortality risk among patients with viral hepatitis (adjusted HR = 2.72; 95% CI = 1.54-4.78; Pinteraction = .048). Our study indicates that PPI use is associated with poor prognosis in NSCLC patients treated with ICIs. Further prospective studies are required to determine the risk-benefit balance of concomitant use of PPIs and ICIs.

Incidence and Clinical Outcomes of Febrile Neutropenia in Adult Cancer Patients with Chemotherapy Using Korean Nationwide Health Insurance Database.

PURPOSE: The aim of this study was to evaluate the episodes of febrile neutropenia (FN) in patients with gastric cancer (GC), colorectal cancer (CRC), lung cancer (LC), and breast cancer (BC); and to identify the incidence and trends of admission rates, as well as factors affecting mortality. MATERIALS AND METHODS: Using nationwide claims data, all new admissions to hospitals for FN were selected. We evaluated the incidence of FN and mortality-related clinical factors in adult cancer patients who received cytotoxic chemotherapy from January 2004 to December 2013. RESULTS: While the incidence of FN increased, the length of hospitalization decreased in Korea. The incidence of FN was 19.8% in LC patients, 15.5% in GC patients, 13.3% in BC patients, and 9.5% in CRC patients. The overall in-hospital mortality of FN was 12.9% and showed a decreasing trend. Admission rates to intensive care units and in-hospital mortality were the highest for lung cancer (15.2% and 19.3%, respectively). Age and sepsis syndrome were risk factors for in-hospital mortality for all cancer types. CONCLUSION: Careful observation and active prophylaxis should be considered for patients at high risk of FN.

Prevalence and Predictive Factors for Upfront Dose Reduction of the First Cycle of First-Line Chemotherapy in Older Adults with Metastatic Solid Cancer: Korean Cancer Study Group (KCSG) Multicenter Study.

Old age alone does not reflect an intolerability to chemotherapy. However, upfront dose reduction (UDR) of the first cycle of first-line palliative chemotherapy has sometimes been chosen by physicians for older adults with metastatic cancer due to concerns regarding adverse events. The development of predictive factors for UDR of palliative chemotherapy would be helpful for treatment planning among older adults. This was a secondary analysis of a study on predicting adverse events of first-line palliative chemotherapy in 296 patients (≥70 years) with solid cancer. We assessed the prevalence of UDR of the first cycle of first-line chemotherapy and the association of UDR with the variables of geriatric assessment (GA) and chemotherapy compliance. Among the 296 patients, 177 (59.8%) patients were treated with UDR. The mean percentage of UDR for the total patient group was 19.2% (range: 4-47%) of the standard dose. In a multivariate analysis, poor performance status (PS) and living without a spouse were independent predictive factors of UDR of first-line palliative chemotherapy in older adults. Patients with UDR showed fewer grade 3-5 adverse events versus the standard dose group. Study completion as planned was significantly higher in the UDR group versus the standard dose group. Older adults with UDR better tolerated chemotherapy than patients with a standard dose.

Bone metastasis and skeletal-related events in patients with solid cancer: A Korean nationwide health insurance database study.

Bone is one of the most common sites of metastasis from advanced solid tumors. Bone metastasis is a leading cause of pain and increases the risk of skeletal-related events (SREs) in cancer patients. In addition to affecting the quality of life, it also increases the medical costs and mortality risk. We aimed to examine the occurrence of bone metastasis and SREs in Korean cancer patients using a nationwide health database. Using claims data from the National Health Insurance Service-National Sample Cohort (2002-2013), we extracted the data of bone metastasis patients diagnosed with any of the seven major cancers in Korea from January 2002 to December 2010. Selected SREs included pathologic fracture, spinal cord compression, radiation therapy, and palliative bone surgery. We used time-to-event analysis to estimate patient survival after bone metastasis. A total of 21,562 newly diagnosed cancer patients were identified; bone metastases developed in 1,849 patients (breast cancer, 18.8%; prostate cancer, 17.5%; lung cancer, 13.7%). The median time from primary cancer diagnosis to bone metastasis was 18.9 months. The cumulative incidence of SREs was 45.1% in all bone metastasis patients. The most common cancer type was lung cancer (53.4%), followed by liver (50.9%), prostate (45.9%), breast (43.6%), and colorectal (40.2%) cancers. Almost all SREs developed 1 month after bone metastasis, except in patients with breast and prostate cancers (median: 5.9 months in breast cancer and 4.7 months in prostate cancer). Survival duration after the development of bone metastasis was < 6 months in stomach, liver, colorectal, and lung cancer patients. Breast and prostate cancer patients survived for > 1 year after the occurrence of SREs. This study reveals the epidemiology of bone metastasis and SREs in Korean cancer patients, and the findings can be used to assess the actual bone health status of cancer patients.

A Randomized Phase II Study of Perioperative Chemotherapy Plus Bevacizumab Versus Postoperative Chemotherapy Plus Bevacizumab in Patients With Upfront Resectable Hepatic Colorectal Metastases.

INTRODUCTION: Whether patients with resectable colorectal liver metastases (CRLM) gain a survival benefit from perioperative chemotherapy remains controversial. The benefit of including bevacizumab in chemotherapy also remains unclear. MATERIAL AND METHODS: Seventy-six patients with CRLM were randomly assigned to either 6 cycles of FOLFOX (folinic acid, 5-fluorouracil, and oxaliplatin)/FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan) with bevacizumab before and after surgery or 12 cycles after surgery. Progression-free survival (PFS) was estimated using the Kaplan-Meier method and compared by the log-rank test. RESULTS: The median PFS of all patients was 37.4 months at 5.4 years follow-up, and the median overall survival (OS) was not reached. The PFS between the perioperative group and the postoperative group did not reveal a statistical difference (P = .280). The OS was significantly better in the perioperative group (hazard ratio [HR], 0.60; 95% confidence interval [CI],) 0.35-1.02; P = .049). In subgroup patients with carcinoembryonic antigens (CEA) ≥ 5 ng/mL or those with over 2 liver metastases, perioperative group had longer OS than postoperative group (CEA: HR, 0.49; 95% CI, 0.25-0.93; P = .030; number of liver metastases: HR, 0.55; 95% CI, 0.30-0.99; P = .049). The largest liver metastases size, disease-free interval, and sidedness did not affect PFS or OS. There was no difference between the 2 groups in postoperative complications with bevacizumab or adverse events during chemotherapy. CONCLUSIONS: In patients with resectable CRLMs, perioperative chemotherapy had no effect on PFS, but improved OS. Patients with high CEA levels or over 2 liver metastases may benefit from perioperative chemotherapy.

Discovery of novel heat shock protein (Hsp90) inhibitors based on luminespib with potent antitumor activity.

A series of isosteric surrogates of the 4-phenyl group in luminespib were investigated as new scaffolds of the Hsp90 inhibitor for the discovery of novel antitumor agents. Among the synthesized surrogates of isoxazole and pyrazole, compounds 4a, 5e and 12b exhibited potent Hsp90 inhibition in ATPase activity and Her2 degradation assays and significant antitumor activity in A2780 and HCT116 cell lines. Animal studies indicated that compared to luminespib, their activities were superior in A2780 or NCI-H1975 tumor xenograft models. A molecular modeling study demonstrated that compound 4a could fit nicely into the N-terminal ATP binding pocket.

Polypharmacy, Inappropriate Medication Use, and Drug Interactions in Older Korean Patients with Cancer Receiving First-Line Palliative Chemotherapy.

BACKGROUND: Polypharmacy is an important issue in the care of older patients with cancer, as it increases the risk of unfavorable outcomes. We estimated the prevalence of polypharmacy, potentially inappropriate medication (PIM) use, and drug-drug interactions (DDIs) in older patients with cancer in Korea and their associations with clinical outcomes. SUBJECTS, MATERIALS, AND METHODS: This was a secondary analysis of a prospective observational study of geriatric patients with cancer undergoing first-line palliative chemotherapy. Eligible patients were older adults (≥70 years) with histologically diagnosed solid cancer who were candidates for first-line palliative chemotherapy. All patients enrolled in this study received a geriatric assessment (GA) at baseline. We reviewed the daily medications taken by patients at the time of GA before starting chemotherapy. PIMs were assessed according to the 2015 Beers criteria, and DDIs were assessed by a clinical pharmacist using Lexi-comp Drug Interactions. We evaluated the association between polypharmacy and clinical outcomes including treatment-related toxicity, and hospitalization using logistic regression and Cox regression analyses. RESULTS: In total, 301 patients (median age 75 years; range, 70-93) were enrolled; the most common cancer types were colorectal cancer (28.9%) and lung cancer (24.6%). Mean number of daily medications was 4.7 (±3.1; range, 0-14). The prevalence of polypharmacy (≥5 medications) was 45.2% and that of excessive polypharmacy (≥10 medications) was 8.6%. PIM use was detected in 137 (45.5%) patients. Clinically significant DDIs were detected in 92 (30.6%) patients. Polypharmacy was significantly associated with hospitalization or emergency room (ER) visits (odds ratio: 1.73 [1.18-2.55], p < .01). Neither polypharmacy nor PIM use showed association with treatment-related toxicity. CONCLUSION: Polypharmacy, PIM use, and potential major DDIs were prevalent in Korean geriatric patients with cancer. Polypharmacy was associated with a higher risk of hospitalization or ER visits during the chemotherapy period. IMPLICATIONS FOR PRACTICE: This study, which included 301 older Korean patients with cancer, highlights the increased prevalence of polypharmacy in this population planning to receive palliative chemotherapy. The prevalence of polypharmacy and excessive polypharmacy was 45.2% and 8.6%, respectively. The prescription of potentially inappropriate medications (PIMs) was detected in 45.5% and clinically significant drug-drug interaction in 30.6% of patients. Given the association of polypharmacy with increased hospitalization or emergency room visits, this study points to the need for increased awareness and intervention to minimize polypharmacy in the geriatric cancer population undergoing chemotherapy. Moreover, specific criteria for establishing PIMs should be adopted for the treatment of older adults with cancer.

Cardiovascular Toxicity of Targeted Therapies for Cancer: An Overview of Systematic Reviews.

BACKGROUND: Several targeted therapies for cancer have been associated with cardiovascular toxicity. The evidence for this association has not been synthesized systematically nor has the quality of evidence been considered. We synthesized systematic review evidence of cardiovascular toxicity of individual targeted agents. METHODS: We searched MEDLINE, Embase, and the Cochrane Database of Systematic Reviews for systematic reviews with meta-analyses of cardiovascular outcomes for individual agents published to May 2020. We selected reviews according to prespecified eligibility criteria (International Prospective Register of Systematic Reviews CRD42017080014). We classified evidence of cardiovascular toxicity as sufficient, probable, possible, or indeterminate for specific cardiovascular outcomes based on statistical significance, study quality, and size. RESULTS: From 113 systematic reviews, we found at least probable systematic review evidence of cardiovascular toxicity for 18 agents, including high- and all-grade hypertension for bevacizumab, ramucirumab, axitinib, cediranib, pazopanib, sorafenib, sunitinib, vandetanib, aflibercept, abiraterone, and enzalutamide, and all-grade hypertension for nintedanib; high- and all-grade arterial thromboembolism (includes cardiac and/or cerebral events) for bevacizumab and abiraterone, high-grade arterial thromboembolism for trastuzumab, and all-grade arterial thromboembolism for sorafenib and tamoxifen; high- and all-grade venous thromboembolism (VTE) for lenalidomide and thalidomide, high-grade VTE for cetuximab and panitumumab, and all-grade VTE for bevacizumab; high- and all-grade left ventricular ejection fraction decline or congestive heart failure for bevacizumab and trastuzumab, and all-grade left ventricular ejection fraction decline/congestive heart failure for pazopanib and sunitinib; and all-grade corrected QT interval prolongation for vandetanib. CONCLUSIONS: Our review provides an accessible summary of the cardiovascular toxicity of targeted therapy to assist clinicians and patients when managing cardiovascular health.

Zoledronic acid and skeletal-related events in patients with bone metastatic cancer or multiple myeloma.

INTRODUCTION: Investigations of ZA effectiveness using large, real-world databases are rare. We examined whether zoledronic acid (ZA) decreased the risk of skeletal-related events (SREs) among patients with bone metastases (BMs) from breast cancer (BC) or prostate cancer (PC), or multiple myeloma (MM) in routine clinical practice. MATERIALS AND METHODS: We conducted a propensity score-matched cohort study using the Korean National Health Insurance database. Our cohort included patients diagnosed with BM after BC or PC, or MM between 2004 and 2015. SRE was defined as having a record of pathologic fracture, spinal cord compression, radiation, or surgery to bone. The incidence of multiple SREs was calculated according to SRE history. We calculated the incidence rate ratio (IRR) to examine the relative difference in the risk of SREs of ZA users compared to those of ZA non-user. RESULTS: Among 111,679 patients, diagnosed with BM and one of the three cancer types, 5608 were included in the analysis after propensity score matching. A decreased risk of SREs was observed for the ZA use in patients with history of SRE in BC [IRR = 0.74, 95% confidence interval (CI) = 0.66-0.83], PC (IRR = 0.86, 95% CI = 0.73-1.02), and MM (IRR = 0.74, 95% CI = 0.59-0.93). For patients without SRE history, ZA use was not associated with decreased risks of SREs, but rather increased the risks (BC: IRR = 1.96, 95% CI 1.87-2.05; PC: IRR = 1.66, 95% CI 1.54-1.80; MM: IRR = 1.92, 95% CI 1.57-2.34). CONCLUSIONS: Our study suggests that the ZA use was associated with a decreased risk of SRE for patients with SRE history. However, no preventive effects of ZA were observed for patients without history.

Serum biomarkers for predicting overall survival and early mortality in older patients with metastatic solid tumors.

OBJECTIVES: We aimed to explore serum biomarkers for predicting survival of older patients with metastatic solid tumors who received first line palliative chemotherapy. MATERIALS AND METHODS: Serum samples were prospectively collected before first-line chemotherapy at 11 academic centers in Korea. All patients were participants in a prospective cohort study of older patients with metastatic solid tumors. Serum levels of C-reactive protein (CRP), CXCL10, SIRT1, VEGF-A, activin A, C-terminal telopeptide of type I collagen (CTx), total 25-hydroxyvitamin D were measured by ELISA and interleukin-6 (IL-6), myostatin, irisin, FGF-19, FGF-21, FGF-23 by Luminex multiplex assay. Overall survival (OS) was determined. RESULTS: Serum samples from 138 patients (median age: 75 years, range: 70-92 years) were collected from February 2014 to December 2016. During a median follow up time of 13.8 months, 73 (52.9%) patients died. Among 13 serum markers, CRP (log-rank, P = 0.009), activin A (P = 0.007), and myostatin (P = 0.047) were significantly correlated with OS in univariate analyses. Activin A (hazard ratio [HR] 2.22, 95% confidence interval [CI] 1.32-3.72; P = 0.003) and myostatin (HR 3.02, 95% CI 1.39-6.57; P = 0.005) were significantly associated with OS after adjustment for other clinical factors. In predicting early (6-month) mortality, two inflammatory markers, IL-6 and CRP, were included in the decision-tree model. CONCLUSION: In older patients with cancer, high serum concentrations of activin A and myostatin were predictive of poor OS. IL-6 and CRP might be useful to select older patients at risk of early mortality. These markers could be incorporated into predictive tools for clinical decision-making and warrant further investigation.

Prospective Validation of The Korean Cancer Study Group Geriatric Score (KG)-7, a Novel Geriatric Screening Tool, in Older Patients with Advanced Cancer Undergoing First-line Palliative Chemotherapy.

PURPOSE: The purpose of this study was to prospectively validate the Korean Cancer Study Group Geriatric Score (KG)-7, a novel geriatric screening tool, in older patients with advanced cancer planned to undergo first-line palliative chemotherapy. MATERIALS AND METHODS: Participants answered the KG-7 questionnaire before undergoing geriatric assessment (GA) and first-line palliative chemotherapy. The performance of KG-7 was evaluated by calculating the sensitivity (SE), specificity (SP), positive and negative predictive value (PPV and NPV), balanced accuracy (BA), and area under the curve (AUC). RESULTS: The baseline GA and KG-7 results were collected from 301 patients. The median age was 75 years (range, 70 to 93 years). Abnormal GA was documented in 222 patients (73.8%). Based on the ≤ 5 cut-off value of KG-7 for abnormal GA, abnormal KG-7 score was shown in 200 patients (66.4%). KG-7 showed SE, SP, PPV, NPV, and BA of 75.7%, 59.7%, 84.4%, 46.0%, and 67.7%, respectively; AUC was 0.745 (95% confidence interval, 0.687 to 0.803). Furthermore, patients with higher KG-7 scores showed significantly longer survival (p=0.006). CONCLUSION: KG-7 appears to be adequate in identifying patients with abnormal GA prospectively. Hence, KG-7 can be a useful screening tool for Asian countries with limited resources and high patient volume.

Predicting cumulative incidence of adverse events in older patients with cancer undergoing first-line palliative chemotherapy: Korean Cancer Study Group (KCSG) multicentre prospective study.

BACKGROUND: Older patients have increased risk of toxicity from chemotherapy. Current prediction tools do not provide information on cumulative risk. METHODS: Patients aged ≥ 70 years with solid cancer were prospectively enrolled. A prediction model was developed for adverse events (AEs) ≥ Grade 3 (G3), based on geriatric assessment (GA), laboratory, and clinical variables. RESULTS: 301 patients were enrolled (median age, 75 years). Median number of chemotherapy cycles was 4. During first-line chemotherapy, 53.8% of patients experienced AEs ≥ G3. Serum protein < 6.7 g/dL, initial full-dose chemotherapy, psychological stress or acute disease in the past 3 months, water consumption < 3 cups/day, unable to obey a simple command, and self-perception of poor health were significantly related with AEs ≥ G3. A predicting model with these six variables ranging 0-8 points was selected with the highest discriminatory ability (c-statistic= 0.646), which could classify patients into four risk groups. Predicted cumulative incidence of AEs ≥ G3 was discriminated according to risk groups. CONCLUSIONS: This prediction tool could identify the risk of AEs ≥ G3 after chemotherapy and provide information on the cumulative incidence of AEs in each cycle. CLINICAL TRIAL ID: WHO ICTRP number, KCT0001071.

Kaposi's Varicelliform-Like Eruption in a Patient Treated with Everolimus for Metastatic Renal Cell Carcinoma: Report of a Rare Case.

Kaposi's varicelliform eruption is a cutaneous eruption caused by the herpes simplex virus and a few other viruses that infect persons with pre-existing dermatosis such as atopic dermatitis. We report the case of a 56-year-old man who was treated with the mammalian target of rapamycin inhibitor, everolimus, for metastatic renal cell carcinoma. He presented with painful, umbilicated vesicles and pustules on his face, genital region, forearms, and legs suggestive of Kaposi's varicelliform eruption. He did not have a history of any visceral viral disease and pre-existing dermatosis. The diagnosis was based on the clinical features. He was treated with acyclovir for 7 days, with improvement of his skin lesions. We discuss the clinical manifestations of the Kaposi varicelliform-like eruption in an immunocompromised patient treated with everolimus.

Overexpression of class III beta tubulin and amplified HER2 gene predict good response to paclitaxel and trastuzumab therapy.

Through this study, we aimed to validate several biomarkers that have been known to possibly predict the outcomes of the trastuzumab and paclitaxel (TP). Human epidermal growth factor 2 (HER2) positive metastatic breast cancer (MBC) patients who had been treated with TP in single institute from 2006 to 2009 were included in this study. For procured formalin fixed paraffin embedded tumor tissues, HER2 amplification index (AI) and polymorphisms of the immunoglobulin G fragment C receptors (FCGR) were assessed as biomarkers to the trastuzumab and expression of class III beta tubulin (bTubIII) was evaluated as a predictive factor to the paclitaxel. Of 46 patients treated with TP, 27 patients could be evaluated for HER2 AI, 31 for bTubIII, and 26 for FCGR gene polymorphism. The median of the HER2 AI was 5.0 (range, 1.4-15.5) and a higher HER2 AI (≥ 5.0) was significantly correlated with better response rate (RR) (80% vs. 42%, P=0.049) and longer progression-free survival (PFS) (13.6 vs. 6.9 months, P=0.023). High bTubIII expression showed higher RRs than did low expression (81% vs. 40%, P=0.040) in addition to longer PFS (16.2 months vs. 8.8 months, P=0.04). However, polymorphisms in FCGR 2A-H131R or FCGR 3A-V158F were not predictive of RR or PFS. Our results suggest that a high HER2 AI and high bTubIII expression could be predictive of the outcomes to TP therapy but no evidence was found in terms of FCGR polymorphisms.

Prognostic and predictive value of carcinoembryonic antigen and cytokeratin-19 fragments levels in advanced non-small cell lung cancer patients treated with gefitinib or erlotinib.

PURPOSE: The prognostic and predictive value of pretreatment serum levels of carcinoembryonic antigen (CEA) and cytokeratin-19 fragments (CYFRA 21-1) were assessed in advanced non-small cell lung cancer (NSCLC) patients treated with gefitinib or erlotinib. MATERIALS AND METHODS: Pretreatment CEA and CYFRA 21-1 were measured in 123 advanced NSCLC patients receiving gefitinib or erlotinib. High CEA levels (h-CEA) were significantly associated with females, patients with adenocarcinoma, and non-smokers. RESULTS: Low CYFRA 21-1 levels (l-CYFRA) were significantly associated with a good performance status (ECOG PS 0-1). The overall response rate (RR) was 27.6%, and higher RR was associated with adenocarcinoma, h-CEA, and epidermal growth factor receptor (EGFR) mutation. Patients with h-CEA had significantly longer progression-free survival (PFS) (p=0.021). Patients with l-CYFRA had significantly longer PFS and overall survival (p=0.006 and p<0.001, respectively). Of note, h-CEA and l-CYFRA had good prognosis in patients with unknown EGFR mutation status or patients with squamous cell carcinoma (p=0.021 and p=0.015, respectively). A good ECOG PS (HR=0.45, p=0.017), h-CEA (HR=0.41, p=0.007), l-CYFRA 21-1 (HR=0.52, p=0.025), and an EGFR mutation (HR=0.22, p<0.001) were independently predictive of a longer PFS. CONCLUSION: h-CEA and l-CYFRA 21-1 may be prognostic and predictive serum markers for higher response and longer survival in patients with advanced NSCLC receiving gefitinib or erlotinib, especially in patients with unknown EGFR mutation status or patients with squamous cell carcinoma.

Elevated serum C-reactive protein as a prognostic marker in small cell lung cancer.

PURPOSE: Elevated C-reactive protein (CRP) is associated with poor prognosis in several tumor types. The purpose of this study was to investigate serum CRP as a prognostic marker in small cell lung cancer (SCLC). MATERIALS AND METHODS: The pretreatment serum CRP level was measured in 157 newly diagnosed SCLC patients, and correlation between serum CRP level and other clinical parameters was analyzed. Multivariate analyses were performed to find prognostic markers using Cox's proportional hazards model. RESULTS: The initial CRP concentration was within the normal range in 72 (45.9%) patients and elevated in 85 (54.1%) patients. There was a significant correlation between serum CRP level and the extent of disease (p<0.001), weight loss (p=0.029) and chest radiation (p=0.001). Median overall survival (OS) in the normal CRP group was significantly longer than with the high CRP group (22.5 months vs. 11.2 months, p<0.001). Extent of disease (p<0.001), age (p=0.025), and performance status (p<0.001) were additional prognostic factors on univariate analysis. On multivariate analysis, elevated serum CRP level was an independent prognostic factor for poor survival (HR=1.8; p=0.014), regardless of the extent of disease (HR=3.7; p<0.001) and performance status (HR=2.2; p<0.001). CONCLUSION: High level of CRP was an independent poor prognostic serum marker in addition to previously well-known prognosticators in patients with SCLC.