Expression Profiles of Circulating MicroRNAs in XELOX-Chemotherapy-Induced Peripheral Neuropathy in Patients with Advanced Gastric Cancer.

Gastric cancer (GC) is one of the most common cancers and a leading cause of cancer deaths around the world. Chemotherapy is one of the most effective treatments for cancer patients, and has remarkably enhanced survival rates. However, it has many side effects. Recently, microRNAs (miRNAs) have been intensively studied as potential biomarkers for cancer diagnosis and treatment monitoring. However, definitive biomarkers in chemotherapy-induced peripheral neuropathy (CIPN) are still lacking. The aim of this study was to identify the factors significant for neurological adverse events in GC patients receiving XELOX (oxaliplatin and capecitabine) chemotherapy. The results show that XELOX chemotherapy induces changes in the expression of hsa-miR-200c-3p, hsa-miR-885-5p, and hsa-miR-378f. Validation by qRT-PCR demonstrated that hsa-miR-378f was significantly downregulated in CIPN. Hsa-miR-378f was identified as showing a statistically significant correlation in GC patients receiving XELOX chemotherapy according to the analysis of differentially expressed (DE) miRNAs. Furthermore, 34 potential target genes were predicted using a web-based database for miRNA target prognostication and functional annotations. The identified genes are related to the peptidyl-serine phosphorylation and regulation of alternative mRNA splicing with enrichment in the gastric cancer, neurotrophin, MAPK, and AMPK signaling pathways. Collectively, these results provide information useful for developing promising strategies for the treatment of XELOX-chemotherapy-induced peripheral neuropathy.

Prognostic value of metabolic activity of the psoas muscle evaluated by preoperative 18F-FDG PET-CT in breast cancer: a retrospective cross-sectional study.

BACKGROUND: This study aimed to evaluate the potential of metabolic activity of the psoas muscle measured by 18F-fluorodeoxyglucose positron emission tomography-computed tomography to predict treatment outcomes in patients with resectable breast cancer. METHODS: The medical records of 288 patients who had undergone surgical resection for stages I-III invasive ductal carcinoma of the breast between January 2014 and December 2014 in Pusan National University Hospital were reviewed. The standardized uptake values (SUVs) of the bilateral psoas muscle were normalized using the mean SUV of the liver. SUVRmax was calculated as the ratio of the maximum SUV of the average bilateral psoas muscle to the mean SUV of the liver. SUVRmean was calculated as the ratio of the mean SUV of the bilateral psoas muscle to the mean SUV of the liver. RESULTS: Univariate analyses identified a higher T stage, higher N stage, estrogen receptor negativity, progesterone receptor negativity, human epidermal growth factor receptor 2 positivity, triple-negative breast cancer, mastectomy (rather than breast-conserving surgery), SUVRmean > 0.464, and SUVRmax > 0.565 as significant adverse factors for disease-free survival (DFS). Multivariate Cox regression analysis revealed that N3 stage (hazard ratio [HR] = 5.347, P = 0.031) was an independent factor for recurrence. An SUVRmax > 0.565 (HR = 4.987, P = 0.050) seemed to have a correlation with shorter DFS. CONCLUSIONS: A higher SUVRmax of the psoas muscle, which could be a surrogate marker of insulin resistance, showed strong potential as an independent prognostic factor for recurrence in patients with resectable breast cancer.

Transdermal granisetron versus palonosetron for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: a multicenter, randomized, open-label, cross-over, active-controlled, and phase IV study.

BACKGROUND: Palonosetron is the second-generation 5-hydroxytryptamine 3 receptor antagonist (5-HT3RA) that has shown better efficacy than the first-generation 5-HT3RA for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC). Granisetron transdermal delivery system (GTDS), a novel transdermal formulation, was developed to deliver granisetron continuously over 7 days. This study compared the efficacy and tolerability of the GTDS to palonosetron for the control of CINV following MEC. MATERIAL AND METHOD: A total of 196 patients were randomized to GP or PG group. In this multicenter, randomized, open-label, cross-over, active-controlled, Phase IV study, GP group was assigned to receive transdermal granisetron (one GTDS patch, 7 days) in the first chemotherapy cycle, palonosetron (iv 0.25 mg/day, 1 days) in the second chemotherapy cycle before receiving MEC, and PG group was assigned to receive palonosetron in the first cycle and GTDS in the second cycle. Primary endpoint was the percentage of chemotherapy cycles achieving complete response (CR; defined as no emetic episodes and no rescue medication use) during the acute phase (0-24 h in post-chemotherapy; non-inferiority comparison with palonosetron). RESULTS: Total 333 cycles (165 in GTDS and 168 in palonosetron) were included in the per protocol analysis. The GTDS cycles showed non-inferiority to palonosetron cycles during the acute phase: CR was achieved by 124 (75.2 %) patients in the GTDS cycles and 134 (79.8 %) patients in the palonosetron cycles (treatment difference, -4.6 %; 95 % confidence interval, -13.6-4.4). There was no significant difference in CR rate during acute phase after the end of the first and second chemotherapy cycle between GP and PG group (p = 0.405, p = 0.074). Patients' satisfaction, assessed using Functional Living Index-Emesis (FLI-E), GTDS cycle were higher than those of palonosetron cycle in GP group (FLI-E score; median 1549.5 in GTDS cycle, median 1670.0 in palonosetron cycle). Both treatments were well tolerated and safe. CONCLUSION: Transdermal granisetron is a good alternative therapeutic option to palonosetron for preventing CINV after MEC.

A prospective, open-label, multicenter study of the clinical efficacy of extended-release hydromorphone in treating cancer pain inadequately controlled by other analgesics.

PURPOSE: The objective of this study was to evaluate whether extended-release hydromorphone (osmotic-controlled release oral delivery system [OROS] hydromorphone) treatment provided pain relief in cancer patients whose pain was inadequately controlled by other analgesics. METHODS: In this prospective, open-label, multicenter trial, patients who have sustained cancer pain with other analgesics were enrolled. After the baseline evaluation (visit 1), OROS hydromorphone was administered. Two evaluations (visits 2 and 3) were made: 29 ± 7 and 57 ± 7 days later, respectively. The primary end point was the pain intensity difference (PID) at visit 3 relative to visit 1 (expressed as percent PID). RESULTS: In total, 879 patients were screened and 432 completed all three visits. Of the 874 full analysis set patients, 343 (39.2 %) improved by more than 30 % PID. Of the 432 per-protocol patients, 282 (65.3 %) improved by more than 30 % PID. At visits 2 and 3, the degree of sleep disturbance, the number of awakenings, and the degree of sleep satisfaction were significantly better than at visit 1 (all P < 0.0001 for both visit 1-visit 2 and visit 1-visit 3). However, this pain relief was not associated with improved quality of life (P = 0.326 and P = 0.055 for visit 1-visit 2 and visit 1-visit 3, respectively). CONCLUSIONS: This study suggested that active pain management using the strong opioid OROS hydromorphone was beneficial in the management of cancer pain that was not controlled by other analgesics.

Endogenous Endophthalmitis From a Klebsiella pneumoniae Liver Abscess: The Incidence, Risk Factors, and Utility of Imaging.

PURPOSE: We investigated the rate of ophthalmologic examinations to detect endogenous endophthalmitis in patients with pyogenic liver abscesses (PLAs) and the incidence and risk factors of endophthalmitis from a PLA caused by Klebsiella pneumoniae (PLA-K). DESIGN: Retrospective case series. METHODS: A total of 536 patients admitted to a university hospital in Korea to treat PLAs during 2012-2022 were included. The proportion of patients who were referred for ophthalmologic examinations was investigated and the incidence of endophthalmitis in 248 patients with PLA-K was calculated. Univariate and multivariate logistic regression analyses were performed to define risk factors including demographic characteristics, underlying diseases, radiologic findings, and systemic conditions. RESULTS: A comprehensive ophthalmologic examination was performed in 73.7% of all patients with PLAs, and the incidence of endophthalmitis from a PLA-K was 7.3%. A liver abscess >5 cm increased the incidence of endogenous endophthalmitis 4-fold compared with smaller abscesses (odds ratio [OR] = 4.01 [95% confidence interval {CI}, 1.02-15.78], P = .047) and portal or hepatic vein thrombophlebitis increased the incidence approximately 4-fold (OR = 4.04 [95% CI, 1.10-14.83], P = .036). Acute cholangitis was approximately 8-fold (OR = 8.33 [95% CI, 1.25-55.71], P = .029), and disseminated intravascular coagulation was approximately 6-fold (OR = 5.76 [95% CI, 1.22-27.21], P = .027) more related to prevalence of endophthalmitis. Other extrahepatic infections increased the incidence approximately 43-fold (OR = 43.06 [95% CI, 10.14-182.90], P < .001). CONCLUSIONS: Clinicians should consider the risk of endogenous endophthalmitis when PLA-K patients have large liver abscesses (>5 cm), acute cholangitis, portal or hepatic vein thrombophlebitis, disseminated intravascular coagulation, or other extrahepatic infections.

Treatment outcomes between concurrent chemoradiotherapy and combination of surgery, radiotherapy, and/or chemotherapy in stage III and IV maxillary sinus cancer: multi-institutional retrospective analysis.

PURPOSE: The incidence of maxillary sinus cancer (MSC) is extremely rare, representing less than 1% of all cancers. Because of its rarity, the management of locally advanced MSC is a challenging issue. The objective of the present study was to retrospectively compare the efficacy of 2 traditional treatment strategies, concurrent chemoradiotherapy (CCRT) versus combination of surgery and radiotherapy and/or chemotherapy (SRCT) in MSC. PATIENTS AND METHODS: From 1989 to 2010, 65 patients with histologically confirmed stage III or IVA/IVB were retrospectively analyzed. RESULTS: The median age of our subjects was 60 years (range 36 to 81). The present study involved 18 women (27.7%) and 47 men (72.3%). Of the 65 patients, 52 (80.0%) had squamous cell carcinoma. The TNM stage was stage III, as determined by the American Joint Committee on Cancer, 6th edition, in 27 patients (41.5%). Stage IVA or IVB was observed in 38 patients (58.5%). Of the 65 patients, 41 underwent treatment. Of these 41 patients, 26 and 15 patients underwent SRCT and CCRT, respectively. During the 75.6 months (range 6.4 to 249.4) of median follow-up, the median progression-free survival duration was 45.1 months (95% confidence interval 0.0 to 142.7). The 5-year overall survival rate was 64.8%. However, the patients who had undergone surgery had better progression-free survival (hazard ratio 2.363, 95% confidence interval 1.098 to 5.085, P = .028) and overall survival (hazard ratio 4.989, 95% confidence interval 1.646 to 15.118, P = .004). The SRCT group had a better progression-free survival (P = .043) and overall survival (P = .029) duration than did the CCRT group. CONCLUSION: SRCT might be superior to CCRT for locally advanced MSC. Additional studies comparing the treatment outcomes of CCRT with SRCT are warranted.

Clinical importance of Bcl-6-positive non-deep-site involvement in non-HIV-related primary central nervous system diffuse large B-cell lymphoma.

In several studies of primary central nervous system lymphoma (PCNSL), deep-site involvement of the brain, as well as age and performance status (PS), were found to be independent prognostic factors. In immunocompetent patients, most primary central nervous system lymphomas (PCNSL) are diffuse large B-cell lymphomas (DLBCL), and recent studies have shown that Bcl-6 would be a favorable prognostic biomarker in PCNS-DLBCL. The objective of this study is to evaluate the clinical importance of the central nervous system (CNS) involvement pattern combined with Bcl-6 expression in PCNS-DLBCL patients. This study included 65 immunocompetent patients with PCNS-DLBCL who underwent treatment with high-dose methotrexate with whole-brain radiotherapy. Immunochemistry was performed for the Bcl-6 and Ki-67 antigens. Forty-four patients were male and 21 patients were female, with median age of 59 years. During the median follow-up period of 26 months, progression-free survival (PFS) was 25% and overall survival (OS) was 31%. Of 65 cases that could be subclassified, 31 patients were Bcl-6 positive and 34 patients were negative. Deep-site involvement of the brain was observed in 31 patients. The Bcl-6-positive group and the group having non-deep-site involvement of the brain were associated with favorable progression-free survival (PFS) (P < 0.001; P < 0.001) and overall survival (OS) (P = 0.001; P < 0.001). Results of univariate analysis showed that age above 60 years, Eastern Cooperative Oncology Group (ECOG) PS above 2, elevated lactate dehydrogenase (LDH) state, complete response (CR), and Bcl-6-positive and deep-site involvement were prognostic factors associated with PFS and OS. Results of multivariate analysis revealed that age above 60 years, ECOG above 2, elevated LDH state, Bcl-6 positivity, and deep-site involvement were independent prognostic factors for prediction of outcome. According to the combined prognostic value of Bcl-6 expression and the deep-site involvement pattern, the subgroup having Bcl-6-positive non-deep-site involvement of the brain showed more favorable PFS and OS than the other subgroups (P < 0.001, P < 0.001), whereas differences of survival among the other three subgroups were not significant (P = 0.054, P = 0.056). Bcl-6 positivity was found to be an independent prognostic factor for survival. Bcl-6 expression was associated with higher PFS and OS in patients having non-deep-site involvement. However, this was counteracted in the group of patients having deep-site involvement of the brain.

Heart Rate Variability as a Non-invasive Objective Parameter for Predicting the Occurrence of Chemotherapy-induced Peripheral Neuropathy in Patients With Gastrointestinal Cancer.

BACKGROUND/AIM: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common chemotoxicities. However, no effective clinical CIPN screening methods have been reported. This study aimed to investigate whether changes in heart rate variability (HRV) could predict the development of CIPN for early symptom control in chemotherapy-prescribed patients with gastrointestinal (GI) cancer. PATIENTS AND METHODS: Fifty-five GI cancer outpatients undergoing palliative chemotherapy including taxanes and/or platinum compounds were enrolled. CIPN was diagnosed using National Cancer Institute Common Toxicity Criteria for Adverse Event (NCI-CTCAE). HRV measures were derived from electrocardiogram signals. RESULTS: Twelve weeks after starting chemotherapy, 39 (70.9%) patients who complained of NCI-CTCAE grade 1-3 sensory changes were diagnosed with CIPN. Standard deviation of normal-to-normal R-R intervals (SDNN), high frequency (HF), low frequency (LF), and LF/HF ratio changed significantly during 3 assessment periods. Percentage changes in SDNN and HF were related to the occurrence of CIPN symptoms. A decision tree model indicated that patients with a rapid percentage change decrease in SDNN and HF were CIPN-positive. CONCLUSION: Using SDNN and HF, our decision tree predicted CIPN occurrence. The changes in HRV may occur earlier than sensory CIPN symptoms.

Treatment with Ramucirumab-paclitaxel in a metastatic gastric cancer patient undergoing hemodialysis: A case report.

RATIONALE: Ramucirumab, a human Ig 1 monoclonal antibody against vascular endothelial growth factor receptor-2, in combination with paclitaxel is a second-line chemotherapy for patients with metastatic gastric cancer. Several reports have suggested that dose adjustments of cetuximab, an anti- epidermal growth factor receptor antibody, are not required in patients with renal impairment. However, the combination chemotherapy of ramucirumab and cytotoxic drug for hemodialysis (HD) patients has not been reported. PATIENT CONCERNS: A 65-year-old man on HD was diagnosed with gastric cancer and underwent a subtotal gastrectomy with D2 lymphadenectomy. Abdominal computed tomography (CT) was examined after completion of 8 cycles of adjuvant chemotherapy with capecitabine combination oxaliplatin. DIAGNOSIS: The patient was diagnosed with advanced gastric cancer at stage IIIb (pT3N2M0) 11 months ago. Unfortunately, 9 months after the start of adjuvant chemotherapy, multiple liver metastases from gastric cancer were found by abdominal CT. INTERVENTIONS: He began receiving weekly paclitaxel(80 mg/m2) and every 15-day ramucirumab (8 mg/kg). HD was performed next day after administration of chemotherapy and repeated 3 times a week. OUTCOMES: He was treated with ramucirumab without dose adjustment. The metastatic liver mass had a partial response, after 2 and 4 cycles of chemotherapy and had a stable disease up to 12 cycles of chemotherapy. No obvious adverse effect was observed during treatment. However, after 14 cycles chemotherapy, follow-up abdominal CT revealed progression disease of multiple liver metastasis and lymph nodes invasion. LESSONS: The paclitaxel chemotherapy with ramucirumab is effective and safe in HD patients with metastatic gastric cancer. As seen in patients with normal kidney function, ramucirumab can be safely administered without a dose reduction.

Prognosis palliative care study, palliative prognostic index, palliative prognostic score and objective prognostic score in advanced cancer: a prospective comparison.

BACKGROUND: Predicting how long a patient with far advanced cancer has to live is a significant part of hospice and palliative care. Various prognostic models have been developed, but have not been fully compared in South Korea. OBJECTIVES: We aimed to compare the accuracy of the Prognosis in Palliative Care Study (PiPS), Palliative Prognostic Index (PPI), Palliative Prognostic Score (PaP) and Objective Prognostic Score (OPS) for patients with far advanced cancer in a palliative care unit in South Korea. METHODS: This prospective study included patients with far advanced cancer who were admitted to a single palliative care unit at the National University Hospital. Variables for calculating the prognostic models were recorded by a palliative care physician. The survival rate was estimated using the Kaplan-Meier method. The sensitivity, specificity, positive predictive value and negative predictive value of each model were calculated. RESULTS: A total of 160 patients participated. There was a significant difference in survival rates across all groups, each categorised through the five prognostic models. The overall accuracy (OA) of the prognostic models ranged between 54.5% and 77.6%. The OA of clinicians' predictions of survival ranged between 61.9% and 81.3%. CONCLUSION: The PiPS, PPI, PaP and OPS were successfully validated in a palliative care unit of South Korea. There was no difference in accuracy between the prognostic models, and OA tended to be lower than in previous studies.

Clinical impact of bulky mass in the patient with primary extranodal diffuse large B cell lymphoma treated with R-CHOP therapy.

Although numerous studies about primary extranodal diffuse large B cell lymphoma (DLBCL) were reported sporadically, the literature of clinical value of immunophenotype and bulky diameter in rituximab era is limited. Ninety-six patients with primary extranodal DLBCL receiving R-CHOP therapy were analyzed to evaluate whether immunophenotype and size of bulky disease are significantly important. The International Prognostic Index was still an important prognostic factor for progression-free survival (PFS) and overall survival (OS; p = 0.003, p = 0.027). Difference of survival between germinal center (GC) type and non-GC type was not different (PFS: p = 0.192; OS: p = 0.197). In two separated groups according to extranodal maximum tumor diameter (EN-MTD) 7.5 cm as cutoff value for survival, the group of EN-MTD > or =7.5 cm had lower PFS and OS than <7.5 cm (PFS: p = 0.001; OS: p = 0.008). In four divided subgroups according to EN-MTD combined with immunophenotype, the subgroup of non-GC type with EN-MTD > or = 7.5 cm had lower PFS and OS compared with the other subgroups (PFS: p < 0.001; OS: p = 0.008). Multivariate analysis revealed that non-GC with EN-MTD > or = 7.5 cm was an independent prognostic parameter (PFS: HR = 5.407, 95%CI = 2.378-12.294, p < 0.001; OS: HR = 4.136, 95%CI = 1.721-9.941, p = 0.002). Bulky primary extranodal DLBCL would be associated with unfavorable outcome especially in non-GC type.

Measurement of tumor volume by PET to evaluate prognosis in patients with head and neck cancer treated by chemo-radiation therapy.

PURPOSE: To evaluate the prognostic value of the metabolic tumor volume measured on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging and other clinical factors in patients treated for locally advanced head-and-neck cancer (HNC) at a single institution. MATERIALS AND METHODS: Between June 2005 and August 2008, 59 patients with HNC that underwent pretreatment FDG-PET studies received neoadjuvant chemotherapy and radiation therapy. Metabolically active tumor regions were delineated on the pretreatment PET scans by a fixed SUV of 2.5. We evaluated the relationship of the 18F-fluorodeoxyglucose-PET maximum standardized uptake value (SUV) and the metabolic tumor volume (MTV) with the progression-free survival (PFS) and overall survival (OS). RESULTS: The MTV and lymph node metastasis were predictive of the PFS and OS. The lymph node status did not correlate with the MTV. A higher MTV of 9.3 cm(3) was significantly associated with an increased risk of recurrence (2.19-fold, p = 0.006) and death (1.62-fold, p = 0.051). Separation of patients with tumor volumes

Clinical value of absolute lymphocyte counts before bortezomib-dexamethasone therapy in relapsed multiple myeloma patients.

A high absolute lymphocyte count (ALC) at diagnosis is known as a surrogate marker of favorable prognosis in newly diagnosed multiple myeloma (MM). Recent studies showed tumor sensitization and enhanced cytotoxicity of bortezomib. We hypothesized that a high ALC before bortezomib treatment would contribute to tumor sensitization and activated cytotoxicity of bortezomib in relapsed MM. Ninety-seven relapsed MM patients who underwent bortezomib-dexamethasone (Vel-Dex) therapy were analyzed. Median follow-up duration was 21 months and median age was 61 years. Complete response (CR) and very good partial response (VGPR) after 2 cycles of Vel-Dex therapy were higher in the high-ALC group (>or=1.1 x 10(9)/l) (CR + VGPR 50.0% in the high-ALC group vs. 10.4% in the low-ALC group, p = 0.001), and stable disease (SD) rate was lower in the high-ALC group (SD 11.8% in the high-ALC group vs. 44.8% in the low-ALC group, p < 0.001). In the univariate analysis, the low-ALC group before therapy was associated with shorter progression-free survival (PFS) [hazard ratio (HR), 2.780; 95% confidence interval (95% CI) 1.703-4.536, p < 0.001]. Multivariate analysis revealed that a low ALC represented an independent predictive factor for PFS (HR 1.937, 95% CI 1.168-3.212, p = 0.010). A low ALC just before Vel-Dex therapy was associated with a poor prognosis in relapsed MM.

Comparison of gemcitabine plus nab-paclitaxel and FOLFIRINOX in metastatic pancreatic cancer.

BACKGROUND: Gemcitabine plus nab-paclitaxel (GA) and modified FOLFIRINOX (FFX) have been widely used as standard first-line treatment in pancreatic cancer. However, it is unclear which regimen is more efficacious. AIM: To evaluate a retrospective analysis comparing the efficacy and safety of FFX and GA as first-line chemotherapeutic regimens in patients with metastatic pancreatic cancer. METHODS: We retrospectively analyzed and compared outcomes in 101 patients who presented with pancreatic cancer and were treated with either GA (n = 54) or FFX (n = 47). Moreover, we performed subgroup analysis based on the neutrophil/lymphocyte ratio (NLR) and Eastern Cooperative Oncology Group (ECOG) performance status. RESULTS: There were no significant differences between two groups in baseline characteristics, except for the ECOG performance status. The median progression-free survival (PFS) (6.43 mo vs 4.90 mo, P = 0.058) was comparable between two groups; however, median overall survival (OS) (10.17 mo vs 6.93 mo, P = 0.008) was longer in patients who received GA regimen. In patients with ECOG 0 (PFS: 8.93 mo vs 5.43 mo, P = 0.002; OS: 16.10 mo vs 6.97 mo, P = 0.000) and those with NLR < 3 (PFS: 8.10 mo vs 6.57 mo, P = 0.008; OS: 12.87 mo vs 9.93 mo, P = 0.002), GA regimen showed higher efficacy. CONCLUSION: GA regimen may be recommended to the patients with NLR < 3 or ECOG 0 status although GA and FFX showed comparable efficacy outcomes in patients with metastatic pancreatic cancer.

First-line chemotherapy in very elderly patients with metastatic pancreatic cancer: Gemcitabine monotherapy vs combination chemotherapy.

BACKGROUND: Combination chemotherapy (gemcitabine plus nab-paclitaxel and FOLFIRINOX) is widely used as the standard first-line treatment for pancreatic cancer. Considering the severe toxicities of combination chemotherapy, gemcitabine monotherapy (G mono) could be used as a first-line treatment in very elderly patients or those with a low Eastern Cooperative Oncology Group status. However, reports on the efficacy of G mono in patients older than 75 years are limited. AIM: To evaluate the efficacy of G mono and combination chemotherapy by comparing their clinical outcomes in very elderly patients with pancreatic cancer. METHODS: We retrospectively analyzed 104 older patients with pancreatic cancer who underwent chemotherapy with G mono (n = 45) or combination therapy (n = 59) as a first-line treatment between 2011 and 2019. All patients were histologically diagnosed with ductal adenocarcinoma. Primary outcomes were progression-free survival and overall survival. We also analyzed subgroups according to age [65-74 years (elderly) and ≥ 75 years (very elderly)]. Propensity score matching was performed to compare the outcomes between the two chemotherapy groups. RESULTS: The baseline characteristics were significantly different between the two chemotherapy groups, especially regarding age, ratio of multiple metastases, tumor burden, and Eastern Cooperative Oncology Group performance status. After propensity score matching, the baseline characteristics were not significantly different between the chemotherapy groups in elderly and very elderly patients. In the elderly patients, the median progression-free survival (62 d vs 206 d, P = 0.000) and overall survival (102 d vs 302 d, P = 0.000) were longer in the combination chemotherapy group. However, in the very elderly patients, the median progression-free survival (147 d and 174 d, respectively, P = 0.796) and overall survival (227 d and 211 d, respectively, P = 0.739) were comparable between the G mono and combination chemotherapy groups. Adverse events occurred more frequently in the combination chemotherapy group than in the G mono group, especially thromboembolism (G mono vs nab-paclitaxel vs FOLFIRINOX; 8.9% vs 5.9% vs 28%, P = 0.041), neutropenia (40.0% vs 76.5% vs 84.0%, P = 0.000), and neuropathy (0% vs 61.8% vs 28.0%, P = 0.006). CONCLUSION: In elderly patients, combination therapy is more effective than G mono. However, G mono is superior for the management of metastatic pancreatic cancer in very elderly patients.

Ramosetron versus Palonosetron in Combination with Aprepitant and Dexamethasone for the Control of Highly-Emetogenic Chemotherapy-Induced Nausea and Vomiting.

PURPOSE: The purpose of this study was to compare ramosetron (RAM), aprepitant (APR), and dexamethasone (DEX) [RAD] with palonosetron (PAL), APR, and DEX [PAD] in controlling highly-emetogenic chemotherapy (HEC)-induced nausea and vomiting. MATERIALS AND METHODS: Patients were randomly assigned (1:1) to receive RAD or PAD:RAM (0.3 mg intravenously) or PAL (0.25 mg intravenously) D1, combined with APR (125 mg orally, D1 and 80 mg orally, D2-3) and DEX (12 mg orally or intravenously, D1 and 8 mg orally, D2-4). Patients were stratified by sex, cisplatin-based chemotherapy, and administration schedule. The primary endpoint was overall complete response (CR), defined as no emesis and no rescue regimen during 5 days of HEC. Secondary endpoints were overall complete protection (CP; CR+nausea score < 25 mm) and total control (TC; CR+nausea score < 5 mm). Quality of life was assessed by Functional Living Index Emesis (FLIE) questionnaire on D0 and D6. RESULTS: A total of 279 patients receiving RAD (n=137) or PAD (n=142) were evaluated. Overall CR rates in RAD and PAD recipients were 81.8% and 79.6% (risk difference [RD], 2.2%; 95% confidence interval [CI], -7.1 to 11.4), respectively. Overall CP and TC rates for RAD and PAD were 56.2% and 58.5% (RD, -2.3%; 95% CI, -13.9 to 9.4) and 47.5% vs. 43.7% (RD, 3.8%; 95% CI, -7.9 to 15.5), respectively. FLIE total score ≥ 108 (no impact on daily life) was comparable between RAD and PAD (73.9% vs. 73.4%, respectively). Adverse events were similar between the two groups. CONCLUSION: In all aspects of efficacy, safety and QOL, RAD is non-inferior to PAD for the control of CINV in cancer patients receiving HEC.

Is the early cyclosporine A level predictive of the outcome of immunosuppressive therapy in severe aplastic anemia?

Immunosuppressive therapy (IST) has provided an alternative treatment option for cure of aplastic anemia patients who cannot receive bone marrow transplantation. Although there have been many recent studies on the efficacy of antithymoglobulin (ATG) combined with cyclosporine A (CsA), there is no data on the correlation between the variability of CsA levels and the response to IST. Therefore, we retrospectively assessed the factors associated with IST efficacy in patients with acquired severe aplastic anemia (SAA). Sixty-six patients were treated with ATG combined with CsA for 6 months. In the response group, the CsA levels were increased rapidly to more than 200 ng/mL within the first 2 wk after starting the IST. However, the non-response group had a pattern of slower increase of the CsA levels. The CsA levels, during the first and second week of treatment with IST, were significantly different in the responders and non-responders. The factors predictive of response to IST and survival were analyzed. The univariate analysis showed that a younger age at the initiation of IST, a high absolute neutrophil count prior to starting IST, a short interval between the diagnosis and initiation of IST, and high CsA levels during the first and second week of IST treatment were positively associated with the response rate and overall survival. The multivariate analysis showed that these four factors were independent factors associated with a longer patient survival. A high response rate was associated with a short interval between diagnosis and initiation of IST as well as high CsA levels during the first and second week of IST. Therefore, early intensification of CsA levels might improve patient outcome.

Oral fluoropyrimidines (capecitabine or S-1) and cisplatin as first line treatment in elderly patients with advanced gastric cancer: a retrospective study.

BACKGROUND: This study aimed to evaluate the safety and efficacy of oral fluoropyrimidines and cisplatin therapy in elderly patients with untreated advanced gastric cancer (AGC) retrospectively. In addition, we evaluated the relative activity and toxicity of these agents in this patient population. METHODS: Clinical data from 72 patients with previously untreated AGC, who were treated with capecitabine/cisplatin and S-1/cisplatin, were reviewed. Oral fluoropyrimidines were administered orally twice a day on Days 1-14. The dose of capecitabine was 1250 mg/m(2) and that of S-1 was 50 mg [body surface area (BSA) < 1.5 m(3)] or 60 mg (BSA > 1.5 m(3)) twice a day. Cisplatin was administered intravenously on Day 1 (before the first dose of capecitabine or S-1) at a dose of 70 mg/m(2) over a 2 h period. The chemotherapy cycle was of 3 weeks (with oral capecitabine or S-1). RESULTS: Thirty-two and 40 patients received the S-1 and capecitabine regimens, respectively, and were included in the analysis. The S-1 protocol had a response rate of 40.6%, a median time-to-progression (TTP) of 5.4 months and a median survival of 9.6 months. The capecitabine had a response rate of 55%, a median TTP of 5.9 months and a median survival of 10.2 months. Each protocol had a similar incidence of Grade 3 or 4 adverse events. However, there was a higher rate of the hand-foot syndrome (6 versus 37%) and diarrhea (25 versus 32%) in the capecitabine group. CONCLUSION: Oral fluoropyrimidines and cisplatin in elderly patients with untreated AGC showed encouraging results. The treatment was well tolerated with a manageable toxicity profile. The comparison of S-1 with capecitabine showed that capecitabine had a slightly higher response rate (statistically not significant) in addition to a higher rate of adverse events such as the hand-foot syndrome and diarrhea. These data should be warranted with further prospective studies.

Influence of lactate dehydrogenase and cyclosporine A level on the incidence of acute graft-versus-host disease after allogeneic stem cell transplantation.

Previous reports have suggested that a high serum cyclosporine A (CsA) level could result in a lower incidence of acute-graft-versus-host disease (aGVHD). An elevated serum lactate dehydrogenase (LDH) level has been reported to be an adverse predictor of outcome in stem cell transplantation (SCT) for acute myeloid leukemia. In this study, we retrospectively analyzed the records of 24 patients who received allogeneic SCT from an HLA-matched sibling donor for acute and chronic myelogenous leukemia. Univariate analysis showed that two factors (the serum CsA level at the third week after SCT and the LDH level at the third week after SCT) were significantly associated with the incidence of aGVHD among several variables (age, sex, stem cell source, cell dose, C-reactive protein, absolute lymphocyte count, conditioning regimens, and time to engraftment). A higher serum level of CsA and lower serum LDH level at the third week after SCT were associated with a lower incidence of aGVHD (P=0.015, 0.030). In multivariate analysis, the serum CsA level (hazard ratio [HR], 0.12; 95% confidence interval [CI], 0.022-0.652, P=0.0014) and serum LDH level (HR, 6.59; 95% CI, 1.197-36.316, P=0.030) at the third week after SCT were found to be independent factors that were significantly associated with the development of aGVHD. We conclude that a high CsA level and low LDH level might predict a low cumulative incidence of aGVHD after allogeneic transplantation from a matched sibling donor.