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Carfilzomib, lenalidomide, and dexamethasone (KRd) effectively improve survival in patients with relapsed and refractory multiple myeloma (RRMM). However, the outcome of KRd treatment in Asian patients reflecting a general RRMM population outside of a clinical trial has not been reported. Fifty-five RRMM patients who were treated with carfilzomib in combination with Rd from the time of the first approval of KRd in the Republic of Korea were analyzed. The median age was 61 years. The percentage of patients with an ECOG performance status ≥ 3, creatinine clearance < 50 mL/min, high-risk cytogenetics, and ≥ 4 lines of prior treatment were 9%, 22%, 31%, and 27%, respectively. Forty-one patients started treatment with KRd, whereas the remaining 14 patients (25%) were added carfilzomib during the Rd treatment. In the whole cohort, the overall response rate was 73% and progression-free survival was 8.8 months. The addition of carfilzomib in patients who were refractory or had disease progression during Rd treatment reattained a response in half of the patients. The advantage of carfilzomib with Rd was significant in patients in the first relapse. Toxicity profile was acceptable, excluding severe infections. Carfilzomib in combination with Rd is effective and has a reasonable adverse event rate in Asian patients with RRMM., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Background: For patients with multiple myeloma (MM) that relapsed after treatment with bortezomib- and lenalidomide-based regimens, there were no other treatment options in Korea until 2016. We aimed to determine the efficacy of thalidomide plus dexamethasone-based regimens in patients with relapsed/refractory MM (RRMM)., Patients and Methods: We conducted a multicenter retrospective analysis in Korea for patients with RRMM treated with thalidomide-based regimens who previously received bortezomib and immunomodulatory agents (IMiDs), including thalidomide and lenalidomide., Results: In 47 patients with RRMM, the median age was 64 years and the median number of previous treatment lines, including bortezomib and IMiDs, was 3. Primary resistance to bortezomib and lenalidomide was observed in 12 (26%) and 8 (17%) patients, respectively. The most common regimen was a combination of thalidomide, cyclophosphamide, and dexamethasone. The overall response rate was 38%; 2 patients (4%) experienced a complete response, and 2 patients (4%) experienced a very good partial response. The overall response rate of patients previously exposed to thalidomide was 53%. The median progression-free survival was 5.9 months, and overall survival was 9.2 months. Patients with disease that responded to the thalidomide-based regimen had better progression-free survival compared to those who did not (median, 8.8 vs. 2.5 months; P = .008). The most common adverse events were anemia (51%) for hematologic toxicities and peripheral neuropathy (30%) for nonhematologic toxicities., Conclusion: Thalidomide-based regimens are potential salvage treatment options for patients with RRMM, even those with disease with prior resistance to IMiDs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Although lenalidomide plus dexamethasone (RD) is a therapeutic option for relapsed/refractory multiple myeloma (RRMM), limited real-world clinical data exist. The purpose of this study was to estimate efficacy and safety of RD in RRMM patients of the clinical practice. Data from patients at 25 university hospitals in South Korea between October 2009 and December 2016 were collected retrospectively. We report the effectiveness and safety of RD in 546 RRMM patients in routine clinical practice in South Korea. Patients (median age, 65 years) typically received median 7 cycles of RD, and 184 (33.7%) patients were treated with 10 or more cycles of RD. Patients with renal impairment (CLCr < 40 mL/min; 10.4%), comorbid conditions (≥ 2; 12.0%), and poor performance status (≥ 2; 25.1%) were included. The overall response rate was 64.2%: complete response (13.1%), very good partial response (VGPR 19.9%). With median follow-up duration of 18.6 months, median PFS and OS were 11.2 months and 25.2 months, respectively. In multivariate analysis, less than 2 comorbid conditions, normal LDH, failed one chemotherapy prior to RD, and ≥ 10 cycles of RD therapy had significantly prolonged PFS (P = 0.007, P = 0.011, P = 0.007, and P < 0.001, respectively). Adverse events were acceptable. RD is effective and safe in real-life clinical practice, including patients with comorbidities. RD is an effective and safe treatment in a real clinical setting which includes patients with comorbidities. Early and continual use of RD treatment may improve RRMM survival outcomes.

The Glasgow Prognostic Score (GPS) serves a prognostic role in several lymphomas. The objectives of the present study were to determine whether GPS predicts clinical outcomes and to compare the utility of four prognostic scores, including GPS, in patients diagnosed with peripheral T-cell lymphoma (PTCL). We selected for this retrospective study 96 patients consecutively diagnosed with PTCL according to the World Health Organization classification from January 2002 to February 2013 and followed up in five different institutions. Low GPS was a good prognostic biomarker of progression-free survival (PFS, P = 0.030) and overall survival (OS, P = 0.013). Estimated 3-year OS rates (low-risk vs. intermediate- or high-risk) by the International Prognostic Index (IPI), the Prognostic Index for T-cell lymphoma (PIT), the International Peripheral T-cell Lymphoma Project (IPTCLP) score, and GPS were 83% vs. 44% (P < 0.001), 68% vs. 37% (P = 0.004), 71% vs. 26% (P < 0.001) and 68% vs. 51% (P = 0.031), respectively. These results indicate that GPS has prognostic value for PTCL. In addition, all four prognostic scores demonstrate their usefulness in assessing PTCL outcomes.

Introduction: BCR-ABL1 mutations require consideration during second-line tyrosine kinase inhibitor selection for patients with chronic myeloid leukemia (CML). The present retrospective analysis compared the frequency of BCR-ABL1 mutations in Asian and white patients in whom imatinib therapy had failed., Patients and Methods: A nonstudy cohort (76 Asian patients from community clinical practices) and 2 study cohorts (29 Asian and 352 white patients from dasatinib phase II and III clinical trials) were identified., Results: In the nonstudy cohort, 80 mutations were identified; the most frequent was T315I (15%), followed by phosphate-binding loop mutations E255K (11%), G250E (10%), and Y253H (10%). Asian patients had a greater proportion of T315I and phosphate-binding loop mutations compared with the white patients. The nonstudy cohort was less likely to have multiple mutations compared with either study cohort. Single mutations highly resistant to dasatinib, nilotinib, and bosutinib were more frequent in the Asian than in the white cohorts., Conclusion: These results suggest that mutational analysis findings will be invaluable for choosing an appropriate second-line tyrosine kinase inhibitor in Asia., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Bortezomib-melphalan-prednisone (VMP) showed superior efficacy versus MP as first-line treatment for transplantation-ineligible multiple myeloma (MM). This study investigated the efficacy of VMP for Korean patients with MM.Overall, 177 MM patients received 9 cycles of VMP in this prospective, multicenter, observational study. The primary endpoint was 2-year progression-free survival (PFS).Thirty-nine (22%) patients were aged ≥ 75 years and 83 (47.4%) patients had International Staging System stage III. A median of 5 cycles were delivered. Overall response rate (ORR) was 72.9%, and complete response (CR) rate was 20.3%. With a median follow-up of 11.9 months, median PFS was 17 months. The 2-year PFS and overall survival (OS) rates were 29.2% and 80.0%, respectively. Median OS was not reached. PFS was significantly different depending on performance status (Eastern Cooperative Oncology Group < 2 vs. ≥ 2; p = 0.0002), β2-microglobulin level (< 5.5 vs. ≥ 5.5 mg/L; p = 0.0481), and cumulative dose of bortezomib (< 35.1 vs. ≥ 35.1 mg/m2; p < 0001). The common adverse events (AEs) were in line with the well-known toxicity profiles associated with VMP.In conclusion, VMP is a feasible and effective front-line treatment for transplant-ineligible older patients with MM in Korea. Continuing therapy with prompt adjustment of treatment according to AEs may be important to improve outcomes of elderly patients.

Background/aims: CD11c is a dendritic cell marker in humans, which potentially induces a cytotoxic effect on lymphoma cells. Forkhead boxP3 (FOXP3) is a regulator of T lymphocyte in the microenvironment of the lymphoma. The principal objective of this study was to determine whether the tumors' microenvironment expressions of CD11c and FOXP3 are predictive of clinical outcomes in diffuse large B-cell lymphoma (DLBCL) patients receiving treatment with rituximab, cyclophosphamide, anthracycline, vincristine, and prednisone (R-CHOP) combination chemotherapy., Methods: The study population consisted of 100 patients with DLBCL. The CD11c and FOXP3 expression in primary tumors' microenvironment were evaluated using an immunohistochemistry (IHC)., Results: CD11c and FOXP3 expression positivity in microenvironment were 25% and 35%, respectively. Each one counted for 1 point. In CD11c and FOXP3 stain, positive was counted as 0 and negative was 1. The points were separated into low risk (0 to 1) and high risk (2) groups. Only the extranodal DLBCL patient group analysis conveyed significant differences of progression-free survival ( p = 0.019) and overall survival ( p = 0.039) between the two groups., Conclusions: We can achieve possible clinical significance of lymphoma tumor microenvironments through CD11c and FOXP3 IHC stains in extranodal DLBCL patients receiving R-CHOP therapy.

We analyzed the treatment responses, toxicities, and survival outcomes of patients with relapsed or refractory multiple myeloma who received daily thalidomide, cyclophosphamide, and dexamethasone (CTD) or daily thalidomide, melphalan, and prednisolone (MTP) at 17 medical centers in Korea. Three-hundred and seventy-six patients were enrolled. The combined chemotherapy of thalidomide, corticosteroid, and an alkylating agent (TAS) was second-line chemotherapy in 142 (37.8%) patients, and third-line chemotherapy in 135 (35.9%) patients. The response rate overall was 69.4%. Patients who were not treated with bortezomib and lenalidomide before TAS showed a higher response rate compared to those who were exposed to these agents. The estimated median progression-free survival and overall survival times were 10.4 months and 28.0 months, respectively. The adverse events during TAS were generally tolerable, but 39 (10.4%) patients experienced severe infectious complications. There were no differences in terms of efficacy between CTD and MTP, but infectious complications were more common in CTD group. TAS is an effective treatment regimen which induces a high response rate in relapsed or refractory multiple myeloma patients. Due to the high incidence of grade 3 or 4 infection, proper management of infection is necessary during the TAS treatment, especially the CTD., (© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

We conducted a retrospective analysis of lenalidomide with dexamethasone for patients with relapsed/refractory multiple myeloma (RRMM) who were treated within the Korean patient access program. Lenalidomide has been approved for RRMM for several years in Europe and North America, but has not been accessible to Asian patients in the past. Between 2008 and 2012, 110 patients from 20 hospitals were enrolled. The overall response rate (ORR) was 43.6 % with 15.4 % of very good partial response (VGPR) or better. The median time to progression (TTP) in this heavily pretreated patient population was 8.0 months, and median overall survival (OS) was 23 months. Hematologic toxicities, fatigue, anorexia, and constipation were the most common adverse events. The number of previous treatment lines, previous exposure to thalidomide, refractoriness to thalidomide and bortezomib, pretreatment white blood cell count (WBC), platelet count, t(14;16), and 17p deletion were significant prognostic factors for TTP, and creatinine clearance, refractoriness to thalidomide and bortezomib, performance status, platelet count, and 17p deletion were significant for OS in univariate analysis. In multivariate analysis, WBC and platelet count were significant prognostic factors for TTP and performance status for OS. For Korean myeloma patients, lenalidomide showed considerable efficacy, and toxicities were comparable to the data published in Europe and North America.

The dose intensity of daunorubicin (DNR) delivered during the induction period represented the major prognostic factor for the outcome of adult acute lymphoblastic leukemia (ALL). The aim of this study was to determine the survival or toxicity of escalated doses of DNR in induction treatment of adult patients with acute lymphoblastic leukemia who are at least 15 years of age. For induction chemotherapy, all patients were given 90 mg/m(2)/day of DNR by continuous intravenous (IV) infusion over 24 h daily on days 1-3, 2 mg of vincristine IV push on days 1 and 8, and 60 mg/m(2)/day of prednisolone per oral (PO) on days 1-14 in conjunction with 4,000 units/m(2)/day of L-asparaginase intramuscular or subcutaneous on days 17-28. The median patient age was 32 years (range, 15-69). Complete remission (CR) was achieved in 169 (88.5 %) patients, while 4 died before CR was reached. Additionally, 11 patients died from leukemia progression, 4 had refractory disease, and 3 had follow-up loss. The median follow-up time was 697 days (range, 12-2,270). The 3-year cumulative incidence of relapse was 49.3 %. The probabilities of disease-free survival and overall survival at 3 years were 46.1 and 43.1 %, respectively. The dose of DNR was 100 % of the target dose, and there were no additional specific toxicities. The results show that escalated doses of DNR in induction chemotherapy are similar with the standard dose in response and toxicities. Our study indicates that a more effective regimen or better chemotherapy agents are needed to improve the CR rate and prolong survival in Philadelphia-negative adult ALL.

Background: The aim of this study is to evaluate the associations between vascular endothelial growth factor (VEGF) Single-nucleotide polymorphisms (SNPs) and clinical outcome in advanced gastric cancer patients treated with oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX)., Methods: Genomic DNA was isolated from whole blood, and six VEGF (-2578C/A, -2489C/T, -1498 T/C, -634 G/C, +936C/T, and +1612 G/A) gene polymorphisms were analyzed by PCR. Levels of serum VEGF were measured using enzyme-linked immunoassays., Results: Patients with G/G genotype for VEGF -634 G/C gene polymorphism showed a lower response rate (22.2%) than those with G/C or C/C genotype (32.3%, 51.1%; P = 0.034). Patients with the VEGF -634 G/C polymorphism G/C + C/C genotype had a longer progression free survival (PFS) of 4.9 months, compared with the PFS of 3.5 months for those with the G/G (P = 0.043, log-rank test). By multivariate analysis, this G/G genotype of VEGF -634 G/C polymorphism was identified as an independent prognostic factor (Hazard ratio 1.497, P = 0.017)., Conclusion: Our data suggest that G/G genotype of VEGF -634 G/C polymorphism is related to the higher serum levels of VEGF, and poor clinical outcome in advanced gastric cancer patients.

We performed a phase II trial to evaluate the efficacy and safety of the modified fludarabine, cytarabine, and attenuated-dose idarubicin (m-FLAI) regimen in elderly acute myeloid leukemia (AML) patients. Elderly (≥60 years) AML patients who had not previously received chemotherapy were enrolled in the study. Patients received two consecutive cycles of m-FLAI chemotherapy as an induction. The m-FLAI regimen comprised fludarabine (25 mg/m(2) , days 1-4), cytarabine (1,000 mg/m(2) , days 1-4), and attenuated-dose idarubicin (5 mg/m(2) , days 1-3). The primary end point was complete remission (CR) rate. Secondary end points were overall survival (OS), event-free survival (EFS), and treatment-related mortality (TRM). There were 108 patients (median age 68.4 years, M:F = 64:44) enrolled in the study. CR was achieved in 56.5% of patients, and the TRM rate was 21.3%. Median OS and median EFS were 10.2 and 6.6 months, respectively. The mortality at 30 and 60 days was 15 and 21%, respectively. Performance status and comorbidity did not have prognostic value in this patient cohort. Bone marrow expression of CD117 was associated with increased EFS and OS. m-FLAI is an effective induction regimen for previously untreated AML in elderly patients. In addition, bone-marrow CD117 expression is an independent favorable prognostic factor in elderly AML patients. (ClinicalTrials.gov number, NCT01247493)., (Copyright © 2012 Wiley Periodicals, Inc.)

Core binding factor (CBF)-positive acute myeloid leukemia (AML) presents a favorable prognosis, except for patients with KIT mutation, especially D816 mutation. The current retrospective study attempted to validate a prognostic role of KIT mutation in 121 Korean patients with CBF AML. The study patients consisted of 121 patients with CBF AML (82 patients with RUNX1/RUNX1T1 [67.8 %] and 39 patients with CBFB/MYH11 [32.2 %]) recruited from eight institutions in Korea. All patients received idarubicin plus cytarabine or behenoyl cytosine arabinoside 3 + 7 induction chemotherapy. The KIT gene mutation status was determined by direct sequencing analyses. A KIT mutation was detected in 32 cases (26.4 %) in our series of patients. The KIT mutation was most frequent in exon 17 (n = 18, 14.9 %; n = 16 with D816 mutation), followed by exon 8 (n = 10, 8.3 %). The presence of KIT D816 mutation was associated with adverse outcomes for the event-free survival (p = 0.03) and for the overall survival (p = 0.02). The unfavorable impact of D816 mutation was more prominent when the analysis was confined to the RUNX1/RUNX1T1 subtype. The KIT mutation was detected in 26.4 % of Korean patients with CBF AML. The KIT D816 mutation demonstrated an unfavorable prognostic implication, particularly in the RUNX1/RUNX1T1 subtype.

Background: Tumor vascular endothelial growth factor (VEGF) is a key angiogenic factor and may have an impact on tumor progression and response to chemotherapy. The insulin-like growth factor (IGF) system is related to cell proliferation and tumor growth. However, there is limited available data regarding the clinical and prognostic significance of VEGF or IGF-1 in advanced gastric cancer. The aim of this study was to evaluate the prognostic significance of serum VEGF and IGF-1 levels in advanced gastric cancer patients who were treated with oxaliplatin/5-fluorouracil (FOLFOX)., Methods: The study population consisted of 100 advanced gastric cancer patients (median age 56 years). Patients were treated with oxaliplatin 85 mg/m(2) as a 2-hour infusion on day 1 plus leucovorin 20 mg/m(2) over 10 min, followed by a 5-fluorouracil (5-FU) bolus 400 mg/m(2) and 22 h of continuous infusion of 600 mg/m(2) on days 1-2. Treatment was repeated in 2-week intervals. The levels of serum VEGF and IGF-1 were measured using enzyme-linked immunoassays., Results: There was a significant correlation between the serum level of VEGF and Lauren's classification (p = 0.030) and previous operations (p = 0.010). IGF-1 was associated with the number of metastases (p = 0.012). The median level of serum VEGF was decreased after FOLFOX chemotherapy (p = 0.034). However, none of the measured serum markers were significantly correlated with response. In univariate analysis, overall survival (p < 0.001) was significantly shorter in patients with high serum levels of VEGF. Multivariate analysis revealed that VEGF was an independent factor for overall survival (HR 2.221; 95% CI 1.377-3.583, p = 0.001). Furthermore, IGF-1 had no significant influence on the clinical outcome., Conclusion: A high level of serum VEGF is an independent prognostic factor in patients with advanced gastric cancer treated with chemotherapy. This may help to identify the patients who are more sensitive to the FOLFOX regimen., (Copyright © 2013 S. Karger AG, Basel.)

Aim: Adjuvant chemoradiation has become a standard of care in the USA. We evaluated the efficacy and toxicity of adjuvant chemoradiation versus chemotherapy in completely resected locally advanced gastric cancer., Methods: Patients with stage IIIA, IIIB and IV (without metastasis) gastric cancer were treated with chemoradiation and 5-fluorouracil/cisplatin (FP) (arm A) or FP (arm B). Arm A consisted of one cycle of FP followed by 4500 cGY to radiation field with capecitabine. One month after completion of radiotherapy, patients received three additional cycles of FP every 3 weeks. Arm B consisted of six cycles of FP., Results: A total of 61 patients were enrolled, of whom 31 were placed in arm A and 30 in arm B. The median follow-up duration was 77.2 months (range 24-92.8 months). We did not find any difference in 3-year disease-free survival between arm A and B (80.0 vs 75.2%, respectively; P = 0.887). There was no significant difference between the arms in 5-year disease-free survival (76.7 vs 59.1%, respectively; P = 0.222) or overall survival (70.1 vs 70.0%, respectively; P = 0.814). Seven patients (22.6%) relapsed in arm A and 12 patients (40%) relapsed in arm B. Grade 3/4 neutropenia occurred in 48.5% of patients in arm A and 22.9% in arm B. Grade 3 nausea or vomiting occurred in 6% in arm A and 14.6% in arm B., Conclusion:   We could not make any conclusion about the benefit of adding radiation to adjuvant chemotherapy., (© 2010 Blackwell Publishing Asia Pty Ltd.)

Background: To determine the activity and toxicities of a low-dose leucovorin plus 5-fluorouracil (5-FU) regimen, combined with irinotecan and administered every 2 weeks (modified FOLFIRI), as a first-line therapy for patients with advanced gastric cancer., Method: Patients were treated with cycles of 150 mg/m irinotecan on day 1 plus 50 mg of LV, followed by a 400 mg/m 5-FU bolus and a 22-hour continuous infusion of 600 mg/m 5-FU on days 1 and 2., Results: The median patient age was 55 years (range, 29-75 years), and 77% (34/44) of the patients had a performance status (Eastern Cooperative Oncology Group) of 0 or 1. Of the 44 patients evaluated for their tumor response, 3 patients (6.8%) and 14 patients (31.8%) achieved a complete and partial response, respectively, with an overall response rate of 38.6% (95% confidence interval, 23.7%-53.6%). 13 patients (29.6%) evidenced a stable disease, and 14 patients (31.8%) progressed during the course of the treatment. The median time to progression and overall survival time were 4.9 months (range, 0.9-22.8 months) and 10.3 months (range, 1.2-29.0 months) from the start of the chemotherapy, respectively. A total of 293 cycles were assessed for toxicity. The major hematologic toxicities included grade 1 to 2 anemia (27.6%), neutropenia (48.8%), and grade 3 to 4 neutropenia (12.6%). There were 7 cycles of neutropenic fever. Nonhematological toxicities were observed grade 3 vomiting (6.8%), grade 3 diarrhea (4.5%), and grade 3 mucositis (2.3%). We noted no treatment-related deaths., Conclusions: The modified FOLFIRI regimen-lowering of irinotecan and LV doses-is a safe and feasible regimen as a first-line therapy for patients with recurrent or metastatic gastric cancer.

Background: Gemcitabine-based chemotherapy is a commonly used first-line treatment for patients with pancreatic and biliary tract cancer. However, a standard second-line chemotherapy regimen has yet to be developed after gemcitabine treatment. We attempted to evaluate the efficacy and safety of a combination of continuous 5-fluorouracil, doxorubicin, and mitomycin-C (conti-FAM) as a second-line treatment in pancreatic and biliary tract cancer., Methods: Patients with advanced pancreatic or biliary tract cancer who were previously treated with gemcitabine-based chemotherapy were enrolled in the study. Chemotherapy was administered as follows: 5-fluorouracil, 800 mg/m2 on days 1 to 5 over 10 hours; mitomycin-C, 8 mg/m2 on day 1; and doxorubicin, 30 mg/m2 on day 1 every 4 weeks., Results: A total of 31 patients received 95 cycles of chemotherapy. Fifteen of the patients had pancreatic cancer. Eleven of the patients had cholangiocarcinoma. Gallbladder cancer was observed in 5 patients. Four (12.9%) patients evidenced partial responses. Eight patients (25.8%) had stable disease. The median time to progression and overall survival time were 2.3 (95% CI: 1.0-3.6) months and 6.7 (95% CI: 4.4-9.0) months, respectively. Major hematologic toxicities included grade 1 to 2 anemia (64.2%), neutropenia (32.6%), thrombocytopenia (20%), and grade 3 to 4 neutropenia (10.5%). The most frequently detected nonhematological toxicities were grade 2 and 3 nausea/vomiting (35.5%). One patient was diagnosed with hemolytic uremic syndrome after 8 cycles of treatment., Conclusion: The conti-FAM regimen seems to constitute a safe and feasible salvage therapy in patients with advanced bilio-pancreatic cancer who had been treated previously via gemcitabine-based chemotherapy.

Oxaliplatin and irinotecan have proven effective in the treatment of gastric cancer. We attempted to determine whether single nucleotide polymorphisms in ERCC1, GST, TS and UGT1A1 predicted overall survival in gastric cancer patients receiving FOLFOX and/or FOLFIRI chemotherapy. Total genomic DNA was extracted from the whole blood of patients. The PCR-restriction fragment length polymorphism technique was applied in order to detect the known variant sites of ERCC1, GST, TS and UGT1A1. The response rate of FOLFOX (N=75) was 24%. Grade 3-4 neutropenia and neurotoxicity were observed at frequencies of 34.7 and 16%, respectively. TTP and OS of first-line administration of FOLFOX (N=35) were 3.1 months (95% CI, 0.1-6.1 months) and 13.9 months (95% CI, 12.2-15.6 months), respectively. Only the GSTM1 positive genotype exhibited a significantly better time to progression (P=0.023). However, significant genotypic variation of TS, GST and ERCC1, which was assumed to affect the activity of oxaliplatin, was not observed to affect RR, toxicity and overall survival. The response rate of FOLFIRI (N=74) was 23%. Grade 3-4 neutropenia and diarrhea were observed in 55.4 and 9.5% of cases, respectively. TTP and OS of first-line administration of FOLFIRI (N=33) was 4.9 months (95% CI, 3.5-6.4 months) and 19.0 months (95% CI, 8.5-29.5 months). The low expression type (2R/2R, 2R/3C and 3C/3C) of TS was associated with a high incidence of grade >or=3 neutropenia. However, significant genotypic variation of UGT1A1, which was assumed to affect irinotecan toxicity, was not observed to affect RR, toxicity or survival. In this study, the GSTM1 positive genotype evidenced a significantly better time to progression in cases of advanced gastric cancer being treated with FOLFOX. The low expression type (2R/2R, 2R/3C and 3C/3C) of TS was associated with a high incidence of grade >or=3 neutropenia in cases of advanced gastric cancer treated with FOLFIRI.

Background: The aim of this study was to determine whether the expression of the excision repair cross-complementing 1 (ERCC1), thymidylate synthase (TS) and glutathione S-transferase pi (GSTpi) predict clinical outcome in patients with advanced colorectal cancer treated with fluorouracil (5-FU)/oxaliplatin chemotherapy., Methods: The study population consisted of 70 patients with advanced colorectal cancer (median age, 54 years). Patients were treated with oxaliplatin 85 mg/m as a 2-hour infusion on days 1 plus leucovorin (LV) 20 mg/m over 10 minutes, followed by 5-FU bolus 400 mg/m and a 22-hour continuous infusion of 600 mg/m from day 1 to 2. Treatment was repeated at 2-week intervals. The expression of ERCC1, TS, and GSTpi in primary tumors was examined using immunohistochemistry., Results: ERCC1, TS, and GSTpi were positive in 55.7%, 68.6%, and 71.4% of cases, respectively. Patients without TS expression were more likely to respond to chemotherapy (P = 0.009). There were no significant differences between response to treatment and the ERCC1 or GSTpi expression pattern (P = 0.768, P = 0.589, respectively). The median overall survival (OS) was significantly longer in patients without ERCC1 expression (P = 0.0474). Patients who were ERCC1 positive combined with TS positive, or those with ERCC1 positive combined with TS positive and GSTpi positive had a poor OS (P = 0.0017, P = 0.0323, respectively). Multivariate analysis revealed that both ERCC1 and TS expression significantly impacted OS (hazard ratio 1.72, P = 0.023)., Conclusion: Immunohistochemical study of ERCC1 and TS may be useful for the prediction of clinical outcome in patients with advanced colorectal cancer treated with 5-FU and oxaliplatin.

High-dose chemotherapy followed by autologous stem cell transplantation (HDT/ASCT) offers a rescue option for T cell lymphoma patients with poor prognosis. However, the effectiveness of HDT/ASCT in patients with various peripheral T cell subtypes, optimal transplant timing, and the prognostic factors that predict better outcomes, have not been identified. We retrospectively investigated the clinical outcomes and prognostic factors for HDT/ASCT in 64 Korean patients with peripheral T cell lymphoma, unspecified (PTCL-U) between March 1995 and February 2007. The median age at transplantation was 44 years (range: 15-63 years). According to the age-adjusted International Prognostic Index (a-IPI) and the prognostic index of PTCL (PIT), 8 patients (12.5%) were in the high-risk group and 16 (26.6%) had the 2-3 PIT factors, respectively. After a median follow-up of 29.7 months, the 3-year overall survival (OS) and progression-free survival (PFS) rates were 53.0% +/- 7.5% and 44.3% +/- 7.0%, respectively. Univariate analysis showed that poor performance status, high lactate dehydrogenase (LDH) levels, high a-IPI score, high PIT classes, failure to achieve complete response (CR) at transplantation, and nonfrontline transplantation were associated with poor OS. Multivariate analysis showed that failure to achieve CR at transplantation (hazard ratio [HR] 2.23; 95% confidence interval [CI] 1.78-7.93) and 2-3 PIT factors (HR 3.76; 95% CI 1.02-5.42) were independent prognostic factors for OS. Failure to achieve CR at transplantation and high PIT are negative predictable factors for survival following HDT/ASCT in patients with PTCL-U.

Primary penile lymphoma is rarely observed in cases of extranodal malignant lymphoma. Owing principally to its rarity, no definite treatment modality has been established. We report the case of a 42-year-old man who presented with hematuria and a painless palpable mass on the penis which had persisted for 2 months. A 1.5 x 1.4 cm round mass was detected in the shaft of the penis. Histopathological examination of the excisional biopsy revealed CD20+ diffuse large B cell lymphoma. The patient was classified as having a stage I(AE) lymphoma. Because radiation often causes considerable early morbidity and later loss of function of the penis, 6 cycles of combination chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisolone) with rituximab were administered at 3-week intervals. After treatment, the patient showed a complete response and has maintained this status for the past 7 months. Multiple options, such as surgical amputation, radiotherapy and chemotherapy, are available for treatment of this condition. However, in order to minimize treatment-related morbidity and to maintain quality of life after treatment, combination chemotherapy including rituximab could be considered the treatment of choice after local excision., (Copyright 2008 S. Karger AG, Basel.)

Aim: To evaluate the combination of bevacizumab with infusional 5-fluorouracil (5-FU), leucovorin (LV) and irinotecan (FOLFIRI) in patients with advanced colorectal cancer (CRC) pretreated with combination regimens including irinotecan and oxaliplatin., Methods: Fourteen patients (median age 56 years) with advanced CRC, all having progressed after oxaliplatin- and irinotecan-based combination chemotherapy, were enrolled in this study. Patients were treated with 2 h infusion of irinotecan 150 mg/m2 on d 1, plus bevacizumab 5 mg/kg iv infusion for 90 min on d 2, and iv injection of LV 20 mg/m2 followed by a bolus of 5-FU 400 mg/m2 and then 22 h continuous infusion of 600 mg/m2 given on two consecutive days every 14 d., Results: The median number of cycles of chemotherapy was six (range 3-12). The response rate was 28.5%, one patient had a complete response, and three patients had a partial response. Eight patients had stable disease. The median time to progression was 3.9 mo (95% CI 2.0-8.7), and the median overall survival was 10.9 mo (95% CI 9.6-12.1). Grade 3/4 neutropenia occurred in five patients, and two of these developed neutropenic fever. Grade 3 hematuria and hematochezia occurred in one. Grade 2 proteinuria occurred in two patients. However, hypertension, bowel perforation or thromboembolic events did not occur in a total of 90 cycles., Conclusion: Bevacizumab with FOLFIRI is well tolerated and a feasible treatment in patients with heavily treated advanced CRC.

Background: Clinical studies regarding chemotherapy for gastric cancer patients with malignant ascites have been classically rather limited in scope, largely because peritoneal seeding produces no measurable lesions, and patients generally exhibited poor performance status. Herein, we have evaluated the efficacy and toxicity of a fortnightly modified FOLFOX-4 (m-FOLFOX) regimen., Methods: Gastric cancer patients with cytologically confirmed malignant ascites were treated with cycles of oxaliplatin at 85 mg/m(2) plus leucovorin 20 mg/m(2) on the first day of treatment, followed by 5-fluorouracil (5-FU) via a 400 mg/m(2) bolus and a 22 h continuous infusion of 600 mg/m(2) 5-FU on Days 1-2 at 2-week intervals., Results: Forty-eight patients participated in this study. Twenty-two patients (45.8%) were treated with m-FOLFOX-4 as a first line palliative treatment. Twenty-one patients (43.8%) were adjudged to have an Eastern Cooperative Oncology Group (ECOG) performance status of 2. Thirty-six patients were assessable and exhibited measurable lesions. Twelve (33.3%) patients evidenced partial responses. Decreases or disappearances of ascites levels were observed in 17 (35.4%) patients. The median time to progression and overall survival time were 3.5 (95% CI: 2.9-4.1) months and 8.4 (95% CI: 4.9-11.9) months, respectively. Major hematologic toxicities included Grades 1-2 anemia (53.9%), neutropenia (41.6%) and, Grades 3-4 neutropenia (15.8%). The most frequently detected non-hematological toxicities were Grades 2 and 3 nausea/vomiting (17%). We noted no deaths related to treatment., Conclusion: The m-FOLFOX-4 regimen utilized herein was determined to be both safe and feasible even for gastric cancer patients with malignant ascites in poor performance status.

Objective: This phase II study was designed to assess the safety and efficacy of a modified FOLFIRI regimen (irinotecan with bi-weekly, low dose leucovorin (ldLV) and bolus and continuous infusion with 5-fluorouracil (5-FU)) as a salvage therapy for patients with advanced or metastatic gastric cancer., Methods: Patients were treated with irinotecan 150 mg/m(2) on day 1 and received ldLV 20 mg/m(2) followed by 5-FU 400 mg/m(2) (bolus) and 5-FU 600 mg/m(2) (22 h continuous infusion) on days 1 and 2 every 14 days., Results: A total of 36 patients were assigned to treatment. The median patient age was 55 years (range 31-70), and 55.6% (20/36) of the patients had performance status (ECOG) of 0 or 1. The median follow-up duration was 15.5 (range 2.6-36.4) months. Of the 30 patients evaluated for their tumor response, three achieved a partial response, with an overall response rate of 10.0% (95% CI 0.0-21.0%). Eleven patients (36.7%) showed stable disease. The median time to progression was 3.3 (95% CI 2.0-4.6) months, and the median overall survival time was 10.9 (95% CI 6.1-15.7) months. The median number of cycles of modified FOLFIRI treatment was 3 (range 1-9 cycles). Grade III or IV neutropenia was observed in 23 cycles (17.6%), and febrile neutropenia occurred in three cycles (2.3%). Grade III nausea/vomiting was found in one patient (2.8%). There was one episode of UGI bleeding, but there were no treatment-related deaths., Conclusion: The modified FOLFIRI regimen described here appears a safe and feasible salvage therapy in advanced gastric cancer patients.

To determine the activity and toxicities of a low dose leucovorin (ldLV) plus fluorouracil (5-FU) regimen, combined with oxaliplatin administered fortnightly (modified FOLFOX-4), as a first-line therapy for patients with advanced gastric cancer. Patients were treated with cycles of oxaliplatin 85 mg/m2 on day 1 plus LV 20 mg/m2, followed by 5-FU a 400 mg/m2 bolus and a 22 hour continuous infusion of 600 mg/m2 5-FU on days 1 - 2 every two week intervals. Forty-five patients were enrolled in this study. Forty-two patients were assessable for response. One of the 42 patients demonstrated complete response, and 20 partial responses, and overall response rate of 50%. The median time to progression and overall survival time were 7.7 months (95% CI: 3.6 - 11.9 months) and 11.2 months (95% CI: 9.1 - 13.3 months), respectively. Major hematologic toxicities included grade 1 - 2 anemia (39.7%), neutropenia (30.4%) and grade 3 - 4 neutropenia (10.9%). Twelve cycles were associated with neutropenic fever. The most common non-hematological toxicities were grade 2 nausea/vomiting (20%). There was no treatment related death. The modified FOLFOX-4 regimen was found to be a safe and effective first line therapy in advanced gastric cancer.

Aim: To evaluate the efficacy and toxicity of postoperative chemoradiation using FP chemotherapy and oral capecitabine during radiation for advanced gastric cancer following curative resection., Methods: Thirty-one patients who had underwent a potentially curative resection for Stage III and IV (M0) gastric cancer were enrolled. Therapy consists of one cycle of FP (continuous infusion of 5-FU 1000 mg/m(2) on d 1 to 5 and cisplatin 60 mg/m(2) on d 1) followed by 4500 cGy (180 cGy/d) with capecitabine (1650 mg/m(2) daily throughout radiotherapy). Four wk after completion of the radiotherapy, patients received three additional cycles of FP every three wk. The median follow-up duration was 22.2 mo., Results: The 3-year disease free and overall survival in this study were 82.7% and 83.4%, respectively. Four patients (12.9%) showed relapse during follow-up. Eight patients did not complete all planned adjuvant therapy. Grade 3/4 toxicities included neutropenia in 50.2%, anemia in 12.9%, thrombocytopenia in 3.2% and nausea/vomiting in 3.2%. Neither grade 3/4 hand foot syndrome nor treatment related febrile neutropenia or death were observed., Conclusion: These preliminary results suggest that this postoperative adjuvant chemoradiation regimen of FP before and after capecitabine and concurrent radiotherapy appears well tolerated and offers a comparable toxicity profile to the chemoradiation regimen utilized in INT-0116. This treatment modality allowed successful loco-regional control rate and 3-year overall survival.