Joung Soon Jang

Prognostic factors in primary diffuse large B-cell lymphoma of adrenal gland treated with rituximab-CHOP chemotherapy from the Consortium for Improving Survival of Lymphoma (CISL).

BackgroundThe objective of this study was to identify prognostic factors for survival in patients with primary diffuse large B-cell lymphoma (DLBCL) of the adrenal gland.MethodsThirty one patients diagnosed with primary adrenal DLBCL from 14 Korean institutions and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) were analyzed.ResultsComplete remission (CR) and overall response rate after R-CHOP chemotherapy were 54.8% and 87.0%. The 2-year estimates of overall survival (OS) and progression-free survival (PFS) were 68.3% and 51.1%. In patients achieving CR, significant prolongations of OS (P = 0.029) and PFS (P = 0.005) were observed. Ann Arbor stage had no influence on OS. There was no significant difference in OS between patients with unilateral involvement of adrenal gland and those with bilateral involvement. When staging was modified to include bilateral adrenal involvement as one extranodal site, early stage (I or II) significantly correlated with longer OS (P = 0.021) and PFS (P < 0.001).ConclusionsContrary to prior reports, our data suggests that outcomes of primary adrenal DLBCL are encouraging using a regimen of R-CHOP, and that achieving CR after R-CHOP is predictive of survival. Likewise, our modified staging system may have prognostic value.

Preventive effect of t,t-conjugated linoleic acid on 12-O-tetradecanoylphorbol-13-acetate-induced inhibition of gap junctional intercellular communication in human mammary epithelial MCF-10A cells.

The anti-tumor promotional effects of t9,t11-conjugated linoleic acid (t9,t11-CLA) and t10,t12-CLA were evaluated on the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inhibition of gap junctional intercellular communication (GJIC) in the human mammary epithelial cell line MCF-10A. The results were compared to those obtained from c9,t11-CLA, which is a more effective anti-tumor promoter on TPA-induced GJIC inhibition in MCF-10A cells than t10,c12-CLA. Cells were treated with 20 μM t9,t11-CLA, t10,t12-CLA, or c9,t11-CLA for 24 h followed by 60 nM TPA for 1 h. Both t9,t11-CLA and t10,t12-CLA equally protected MCF-10A cells from TPA-induced inhibition of GJIC with inferior efficacy to c9,t11-CLA.The protection was due to the ameliorated phosphorylation of connexin43 via suppression of extracellular signal-regulated kinases (ERK1/2) activation. Suppression of TPA-induced reactive oxygen species (ROS) generation by t9,t11-CLA and t10,t12-CLA was less effective, relative to c9,t11-CLA. The results suggest that the anti-promotional activities of t9,t11-CLA and t10,t12-CLA are equal but less potent than c9,t11-CLA in TPA-treated MCF-10A cells. The activity might be mediated by the attenuation of ROS production in MCF-10A cells by preventing the downregulation of GJIC during the cancer promotion stage.

Outcomes of Third-Line Docetaxel-Based Chemotherapy in Advanced Gastric Cancer Who Failed Previous Oxaliplatin-Based and Irinotecan-Based Chemotherapies.

Purpose Little is known about outcomes in the use of third-line chemotherapy in cases of advanced gastric cancer (AGC). The primary aim of this retrospective study was to evaluate outcomes of docetaxel-based chemotherapy in patients with AGC that progressed after both oxaliplatin-based and irinotecan-based regimens. Materials and Methods Eligible patients were those with AGC who had previous chemotherapy including fluoropyrimidine and oxaliplatin as well as fluoropyrimidine and irinotecan and who received subsequent docetaxel-based chemotherapy. Thirty-five patients were retrospectively recruited from 5 medical centers in Korea. Patients received either weekly or 3 weekly with docetaxel +/- cisplatin. Results Thirty-one out of 35 patients were evaluated for treatment response. A total of 94 cycles of chemotherapy (median, 2; range, 1 to 7) were administered. The overall response rate was 14.3%, and the disease control rate was 45.7%. The median progression-free survival (PFS) was 1.9 months (95% confidence interval [CI], 1.1 to 2.7 months). The median overall survival (OS) was 3.6 months (95% CI, 2.8 to 4.4 months). PFS and OS were significantly prolonged in patients of the Eastern Cooperative Oncology Group, with performance status of 0 or 1 in multivariate analysis (PFS: hazard ratio[HR], 0.411; 95% CI, 0.195 to 0.868; p=0.020 and OS: HR, 0.390; 95% CI, 0.184 to 0.826; p=0.014, respectively). Four of the 35 patients enrolled in the study died due to infection associated with neutropenia. Conclusion Our findings suggest that salvage docetaxel-based chemotherapy is a feasible treatment option for AGC patients with good performance status (PS), whereas chemotherapy for patients with poor PS (PS≤2) should be undertaken with caution for those who previously failed oxaliplatin- and irinotecan-based regimens.

Differential inhibitory effects of conjugated linoleic acid isomers on mouse forestomach neoplasia induced by benzo(a)pyrene.

The differential anticarcinogenic activity of conjugated linoleic acid (CLA) isomers, including c9,t11-CLA, t10,c12-CLA, and t,t-CLA, was examined in a mouse forestomach carcinogenesis regimen induced by benzo(a)pyrene (BP). Female ICR mice (6-7 weeks of age, 26 +/- 1 g) were divided into six groups (30 mice/group, 5 mice/cage): control, linoleic acid, CLA, c9,t11-CLA, t10,c12-CLA, and t,t-CLA. Each mouse was orally given 0.1 mL of sample and 0.1 mL of olive oil on Monday and Wednesday and BP (2 mg in 0.2 mL of olive oil) on Friday. This cycle was repeated four times. Twenty-three weeks later, the experiment was terminated for tumor analysis. t,t-CLA significantly reduced (p < 0.05) both tumor number and tumor size per mouse, relative to CLA and c9,t11-CLA, but similar to t10,c12-CLA. Reduction in tumor incidence by t,t-CLA (84.6%) was similar to that by CLA, c9,t11-CLA, and t10,c12-CLA, but it was significantly reduced (p < 0.05), relative to 100% linoleic acid and control. t,t-CLA elevated the apoptotic index to 35%, relative to 23% for CLA, 21% for c9,t11-CLA, 29% for t10,c12-CLA, 7% for linoleic acid, and 4% for control. t,t-CLA up-regulated the expression of the Bax gene and activated caspase-3 enzymes but down-regulated expression of the Bcl-2 gene. Cytosolic phospholipase A(2) activity was not affected by the CLA isomers tested. These results suggest that t,t-CLA has superior anticarcinogenic potential on BP-induced mouse forestomach neoplasia to CLA, c9,t11-CLA, and t10,c12-CLA, via the induction of apoptosis through mitochondrial dysfunction.

A prospective multicentre phase II study of cisplatin and weekly docetaxel as first-line treatment for recurrent or metastatic nasopharyngeal cancer (KCSG HN07-01)

BACKGROUND The purpose of this phase II study was to determine the efficacy and toxicity of cisplatin and weekly docetaxel combination chemotherapy as a first-line treatment in patients with recurrent or metastatic nasopharyngeal cancer. PATIENTS AND METHODS Recurrent or metastatic nasopharyngeal cancer patients were enrolled and received a combination of weekly docetaxel (35 mg/m(2) on Day1 and Day8) and cisplatin (70 mg/m(2) D1) every 21 days, for up to a maximum of 6 cycles. The primary endpoint was objective response rate, and the secondary endpoints included toxicity of combination chemotherapy, progression-free survival, overall survival and 1-year survival rate. RESULTS In total, 47 patients were enrolled and analysed, and 46 patients (97.9%) completed the planned protocol. In an intent-to-treat analysis, 6 patients (12.8%) achieved complete response (CR) and 27 patients (57.4%) showed partial response (PR), with an objective response rate of 70.2%. The median progression-free survival and overall survival were 9.6 months (95% C.I. 5.7-13.5 months) and 28.5 months (95% C.I. 16.9-40.1 months), respectively, and the 1-year survival rate was 89.9%. The common grade 3 adverse events were stomatitis (1.2%), neutropenia (0.8%), anaemia (0.8%), infection (0.8%) and diarrhoea (0.8%). Grade 4 adverse events were not observed in this study. CONCLUSIONS The combination chemotherapy of cisplatin and weekly docetaxel is highly effective and shows favourable toxicity as a first-line chemotherapy in patients with recurrent or metastatic nasopharyngeal cancer.

Ramosetron Versus Ondansetron in Combination With Aprepitant and Dexamethasone for the Prevention of Highly Emetogenic Chemotherapy-Induced Nausea and Vomiting: A Multicenter, Randomized Phase III Trial, KCSG PC10-21

BACKGROUND A combination of serotonin receptor (5-hydroxytryptamine receptor type 3) antagonists, NK-1 receptor antagonist, and steroid improves the complete response (CR) of chemotherapy-induced nausea and vomiting (CINV) in cancer patients. Ramosetrons efficacy in this triple combination regimen has not been investigated. This prospective, multicenter, single-blind, randomized, phase III study compares a combination of ramosetron, aprepitant, and dexamethasone (RAD) with a combination of ondansetron, aprepitant, and dexamethasone (OAD) to prove the noninferiority of RAD in controlling highly emetogenic CINV. METHODS Aprepitant and dexamethasone were orally administered for both arms. Ramosetron and ondansetron were intravenously given to the RAD and OAD groups. The primary endpoint was no vomiting and retching and no need for rescue medication during the acute period (day 1); the noninferiority margin was -15%. RESULTS A total of 299 modified intention-to-treat cancer patients who received RAD (144 patients) and OAD (155 patients) were eligible for the efficacy analysis. The CR rates of RAD versus OAD were 97.2% versus 93.6% during the acute period, 77.8% versus 73.6% during the delayed period (day 2-5), and 77.1% versus 71.6% during the overall period. Furthermore, RAD was noninferior to OAD in subgroups stratified by age, cancer type, chemotherapeutic agents, and schedule. Repeated measures analysis showed that in male patients, RAD was superior to OAD. Profiles of adverse events were similar in both groups. CONCLUSION RAD is as effective and tolerable as OAD for CINV prevention in patients receiving highly emetogenic chemotherapy. Ramosetron could be considered one of the best partners for aprepitant.

A randomized, phase II study of gefitinib alone versus nimotuzumab plus gefitinib after platinum-based chemotherapy in advanced non-small cell lung cancer (KCSG LU12-01)

We aimed to evaluate the efficacy of dual inhibition of epidermal growth factor receptor (EGFR) with nimotuzumab (EGFR monoclonal antibody) plus gefitinib (EGFR-tyrosine kinase inhibitor) in advanced non-small cell lung cancer (NSCLC) after platinum-based chemotherapy. An open label, randomized, phase II trial was conducted at 6 centers; 160 patients were randomized (1:1) to either gefitinib alone or nimotuzumab (200 mg, i.v. weekly) plus gefitinib (250 mg p.o. daily) until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS) at 3 months. Of the total 160 enrolled patients, 155 (77: gefitinib, 78: nimotuzumab plus gefitinib) received at least one dose and could be evaluated for efficacy and toxicity. The majority had adenocarcinoma (65.2%) and ECOG performance status of 0 to 1 (83.5%). The median follow-up was 22.1 months, and the PFS rate at 3 months was 48.1% in gefitinib and 37.2% in nimotuzumab plus gefitinib (P = not significant, NS). The median PFS and OS were 2.8 and 13.2 months in gefitinib and 2.0 and 14.0 months in nimotuzumab plus gefitinib. Combined treatment was not associated with superior PFS to gefitinib alone in patients with EGFR mutation (13.5 vs. 10.2 months in gefitinib alone, P=NS) or those with wild-type EGFR (0.9 vs. 2.0 months in gefitinib alone, P=NS). Combined treatment did not increase EGFR inhibition-related adverse events with manageable toxicities. The dual inhibition of EGFR with nimotuzumab plus gefitinib was not associated with better outcomes than gefitinib alone as a second-line treatment of advanced NSCLC (NCT01498562).

Erratum to: Efficacy and safety of aprepitant for the prevention of chemotherapy-induced nausea and vomiting during the first cycle of moderately emetogenic chemotherapy in Korean patients with a broad range of tumor types (Supportive Care in Cancer, (2017), 25, 3, (801-809), 10.1007/s00520-016-3463-0)

Unfortunately, the original version of this article contained errors. The names of Sung Yong Lee and Cho Eun Kim were incorrectly captured and are now corrected in this article. Affiliation 12 is also corrected. The baseline demographics table (Table 2) incorrectly reported percentages calculated out of the total population in each chemotherapy group, instead of out of the total population (as with the rest of the table). Below are the correct percentages:

Antiemetic Corticosteroid Rotation from Dexamethasone to Methylprednisolone to Prevent Dexamethasone‐Induced Hiccup in Cancer Patients Treated with Chemotherapy: A Randomized, Single‐Blind, Crossover Phase III Trial

BACKGROUND To assess whether the rotation of dexamethasone to methylprednisolone decreases the intensity of dexamethasone-induced hiccup (DIH) in cancer patients treated with chemotherapy. MATERIALS AND METHODS Adult patients who experienced DIH within 3 days after the administration of dexamethasone as an antiemetic were screened. Eligible patients were randomly assigned to receive dexamethasone (n = 33) or methylprednisolone (n = 32) as an antiemetic (randomization phase). In the next cycle of chemotherapy, the dexamethasone group received methylprednisolone and vice versa in the methylprednisolone group (crossover phase). The primary endpoint was the difference in hiccup intensity as measured using the numeric rating scale (NRS) between two groups. RESULTS No female patients were enrolled, although the study did not exclude them. At the randomization phase, hiccup frequency was 28/33 (84.8%) in the dexamethasone group versus 20/32 (62.5%) in the methylprednisolone group (p = .04). Intensity of hiccup was significantly higher in the dexamethasone group than that in the methylprednisolone group (mean NRS, 3.5 vs. 1.4, p < .001). At the crossover phase, hiccup intensity was further decreased after the rotation of dexamethasone to methylprednisolone in the dexamethasone group (mean NRS, 3.5 to 0.9, p < .001), while it was increased by rotating methylprednisolone to dexamethasone in the methylprednisolone group (mean NRS, 1.4 to 3.3, p = .025). There were no differences in emesis intensity between the two groups at either the randomization or crossover phases. Clinicaltrials.gov identifier: NCT01974024. CONCLUSION Dexamethasone-induced hiccup is a male-predominant phenomenon that can be ameliorated by rotating dexamethasone to methylprednisolone without compromising the antiemetic efficacy. IMPLICATIONS FOR PRACTICE In this randomized, multicenter, phase III trial, hiccup intensity was significantly lower when the antiemetic corticosteroid was rotated from dexamethasone to methylprednisolone without a change in emesis intensity than that when dexamethasone was maintained. At the crossover phase, hiccup intensity was increased again if dexamethasone was readministered instead of methylprednisolone. The present study demonstrated that dexamethasone-induced hiccup can be improved by rotating from dexamethasone to methylprednisolone without compromising its antiemetic efficacy.

Combination Chemotherapy with Mitomycin C, Vinorelbine, and Cisplatin (MVrP) in Patients with Advanced Non-Small Cell Lung Cancer.

PURPOSE A phase II study was conducted in patients with advanced non-small cell lung cancer (NSCLC) in order to evaluate the efficacy and toxicity of the combination chemotherapy regimen of mitomycin C, vinorelbine, and cisplatin (MVrP). MATERIALS AND METHODS Between June 1996 and December 2000, fifty-nine patients with unresectable stage IIIB to IV, pathologically documented NSCLC were enrolled in this study. One cycle consisted of mitomycin C 10 mg/m2 i.v. day 1, vinorelbine 30 mg/m2 i.v. days 1 & 15, and cisplatin 80 mg/m2 i.v day 1 and the next cycle consisted of vinorelbine 30 mg/m2 i.v. days 29 & 43, and cisplatin 80 mg/m2 i.v day 29. Each cycle was alternated and treatments were repeated every 8 weeks. RESULTS We were able to evaluate fifty-three of 59 patients. Objective responses were seen in 22 (41.5%) patients (CR 0%, PR 41.5%). The median duration of response was 13.7 weeks and the median time to progression was 17.7 weeks. The median overall survival was 45.6 weeks. There was a significantly longer survival seen in responders (p=0.041). The toxicities of this regimen were acceptable without treatment related toxic death. CONCLUSION This study suggests that a combination regimen of mitomycin C, vinorelbine, and cisplatin is relatively effective and well tolerated for the treatment of advanced NSCLC.