Jae-Cheol Jo

Docetaxel monotherapy as a second-line treatment after failure of fluoropyrimidine and platinum in advanced gastric cancer: experience of 154 patients with prognostic factor analysis.

OBJECTIVE To investigate the efficacy and safety of docetaxel monotherapy as salvage chemotherapy for advanced gastric cancer (AGC) in clinical practice and to determine the prognostic factors in these patients. METHODS We retrospectively reviewed the medical records of patients with AGC for whom fluoropyrimidine and platinum had previously failed and who had received docetaxel salvage monotherapy between December 2000 and March 2006. Docetaxel was administered at a dose of 75 mg/m(2) intravenously every 3 weeks with dexamethasone prophylaxis. RESULTS A total of 154 patients received 583 cycles of docetaxel with a median of three cycles per patient (range 1-10). The median age was 54 years (range 27-75 years). The objective response rate of 86 patients with measurable lesions was 14%, with 1 complete response and 11 partial responses, with a median response duration of 5.6 months. An additional 25 patients achieved stable disease. The median time to progression (TTP) for all patients was 2.6 months [95% confidence interval (CI), 2.2-2.9] and the median overall survival (OS) from the start of docetaxel chemotherapy was 7.2 months (95% CI, 5.9-8.5). The chemotherapy was generally well tolerated. Multivariate analysis showed that the Eastern Cooperative Oncology Group (ECOG) performance status (0 or 1 versus 2) was an independent prognostic factor for both TTP and OS. Disease status indicative of a relatively small tumor burden (resected metastatic or recurrent tumor) was a predictor for better TTP and good differentiation of the tumor was a predictor for better OS. CONCLUSION Docetaxel 75 mg/m(2) is relatively active and tolerable as a second-line salvage treatment after failure of fluoropyrimidine and platinum in general clinical practice for AGC.

Phase III trial of concurrent thoracic radiotherapy with either first- or third-cycle chemotherapy for limited-disease small-cell lung cancer

BACKGROUND We compared late thoracic radiotherapy (TRT) with early TRT in the treatment of limited-disease small-cell lung cancer (LD-SCLC). PATIENTS AND METHODS Patients with LD-SCLC received four cycles of etoposide plus cisplatin every 21 days. Patients were randomly assigned to receive either TRT administered concurrently with the first cycle (early TRT) or the third cycle (late TRT) of chemotherapy. The primary end point was complete response rate. RESULTS Two hundred twenty-two patients were randomly assigned.Late TRT was not inferior to early TRT in terms of the complete response rate (early v late; 36.0% v 38.0%). Other efficacy measures including overall survival [median, 24.1 v 26.8 months;hazard ratio (HR) 0.93; 95% CI = 0.67–1.29] and progression free survival (median, 12.4 v 11.2 months; HR 1.09; 95%CI = 0.80–1.48) were not different between two arms. No statistical difference was noted in the pattern of treatment failures.However, neutropenic fever occurred more commonly in the early TRT arm than the late TRT arm (21.6% v 10.2%; P = 0.02) [corrected]. CONCLUSION In LD-SCLC treatment, TRT starting in the third cycle of chemotherapy seemed to be noninferior to early TRT, and had a more favorable profile with regard to neutropenic fever.

Clinical features and prognostic model for extranasal NK/T‐cell lymphoma

The clinical features of extranodal natural killer (NK)/T‐cell lymphoma (ENKL) that originates in extranasal sites are less well defined than those of ENKL that originates in nasal sites. Therefore, we compared the clinical characteristics and prognoses of patients with nasal ENKL and patients with extranasal ENKL.

Rosmarinic acid potentiates ATRA-induced macrophage differentiation in acute promyelocytic leukemia NB4 cells

Rosmarinic acid (RA, an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid) has a number of biological activities, but little is known about anti-leukemic activities of RA combined with all-trans retinoic acid (ATRA) against acute promyelocytic leukemia (APL) cells. We examined the differentiation marker, CD11b, in bone marrow cells (BMC) of an APL patient, in NB4 cells (APL cell line), and in normal BMC and peripheral blood mononuclear cells (PBMC) of healthy subjects by flow cytometric analysis. ATRA/RA induced expression of CD11b in the BMC of the APL patient and in NB4 cells, but not in normal BMC or PBMC. Therefore, we realized that RA potentiated ATRA-induced macrophage differentiation in APL cells. Further characterization of the induced macrophages showed that they exhibited morphological changes and were able to phagocytose and generate reactive oxygen species. Th also had typical expression of C-C chemokine receptor type 1 (CCR1), CCR2, and intercellular adhesion molecule-1 (ICAM-1). Moreover, the expression of CD11b(+) and CD14(+) cells depended on ERK-NF-κB axis activation. Together, these results indicate that RA potentiates ATRA-induced macrophage differentiation in APL cells. Thus, RA may play an important role as an appurtenant differentiation agent for functional macrophage differentiation in APL. Additionally, the differentiated macrophages might have a normal life span and, they could die. These data indicate that co-treatment with RA and ATRA has potential as an anti-leukemic therapy in APL.

Dasatinib Accelerates Valproic Acid-Induced Acute Myeloid Leukemia Cell Death by Regulation of Differentiation Capacity

Dasatinib is a compound developed for chronic myeloid leukemia as a multi-targeted kinase inhibitor against wild-type BCR-ABL and SRC family kinases. Valproic acid (VPA) is an anti-epileptic drug that also acts as a class I histone deacetylase inhibitor. The aim of this research was to determine the anti-leukemic effects of dasatinib and VPA in combination and to identify their mechanism of action in acute myeloid leukemia (AML) cells. Dasatinib was found to exert potent synergistic inhibitory effects on VPA-treated AML cells in association with G1 phase cell cycle arrest and apoptosis induction involving the cleavage of poly (ADP-ribose) polymerase and caspase-3, -7 and -9. Dasatinib/VPA-induced cell death thus occurred via caspase-dependent apoptosis. Moreover, MEK/ERK and p38 MAPK inhibitors efficiently inhibited dasatinib/VPA-induced apoptosis. The combined effect of dasatinib and VPA on the differentiation capacity of AML cells was more powerful than the effect of each drug alone, being sufficiently strong to promote AML cell death through G1 cell cycle arrest and caspase-dependent apoptosis. MEK/ERK and p38 MAPK were found to control dasatinib/VPA-induced apoptosis as upstream regulators, and co-treatment with dasatinib and VPA to contribute to AML cell death through the regulation of differentiation capacity. Taken together, these results indicate that combined dasatinib and VPA treatment has a potential role in anti-leukemic therapy.

Topical vitamin K1 may not be effective in preventing acneiform rash during cetuximab treatment in patients with metastatic colorectal cancer

BACKGROUND Several studies have described the efficacy of topical vitamin K1 cream in the prevention and treatment of acneiform rash during cetuximab treatment. OBJECTIVES An interventional study with a historical control was conducted to investigate the efficacy of vitamin K1 cream for acneiform rash associated with cetuximab. METHODS For the historical control, data were collected from 40 patients with metastatic colorectal cancer who had participated in a previous clinical trial of cetuximab plus irinotecan. The experimental group consisted of 61 patients who were instructed to prophylactically apply topical vitamin K1 cream beginning on the first day of cetuximab treatment. The incidence, severity, and time to occurrence of acneiform rash were compared between groups. RESULTS The incidence of grade≥2 acneiform rash after 4 weeks of cetuximab treatment was 42.5% in the historical control group and 55.5% in the experimental group. The median time to grade≥2 rash in the experimental group was 4 weeks compared to 6 weeks in the historical control group (p=0.340). By multivariate analysis, male gender was the only independent risk factor for grade 2 or worse acneiform rash (HR=2.49; 95% CI, 1.27-4.88; p=0.007). Prophylactic application of topical vitamin K1 cream did not decrease the risk of acneiform rash (HR=1.33; 95% CI, 0.57-3.10; p=0.507). CONCLUSIONS The prophylactic application of topical vitamin K1 cream did not translate into clinically meaningful benefit in terms of reducing acneiform rash in patients with metastatic colorectal cancer treated with cetuximab.

Serum CA 19-9 as a prognostic factor in patients with metastatic gastric cancer.

To evaluate tumor markers as prognostic factors in patients with metastatic or recurrent gastric cancer receiving first‐line chemotherapy.

Radotinib Induces Apoptosis of CD11b+ Cells Differentiated from Acute Myeloid Leukemia Cells

Radotinib, developed as a BCR/ABL tyrosine kinase inhibitor (TKI), is approved for the second-line treatment of chronic myeloid leukemia (CML) in South Korea. However, therapeutic effects of radotinib in acute myeloid leukemia (AML) are unknown. In the present study, we demonstrate that radotinib significantly decreases the viability of AML cells in a dose-dependent manner. Kasumi-1 cells were more sensitive to radotinib than NB4, HL60, or THP-1 cell lines. Furthermore, radotinib induced CD11b expression in NB4, THP-1, and Kasumi-1 cells either in presence or absence of all trans-retinoic acid (ATRA). We found that radotinib promoted differentiation and induced CD11b expression in AML cells by downregulating LYN. However, CD11b expression induced by ATRA in HL60 cells was decreased by radotinib through upregulation of LYN. Furthermore, radotinib mainly induced apoptosis of CD11b+ cells in the total population of AML cells. Radotinib also increased apoptosis of CD11b+ HL60 cells when they were differentiated by ATRA/dasatinib treatment. We show that radotinib induced apoptosis via caspase-3 activation and the loss of mitochondrial membrane potential (ΔΨm) in CD11b+ cells differentiated from AML cells. Our results suggest that radotinib may be used as a candidate drug in AML or a chemosensitizer for treatment of AML by other therapeutics.

Yttrium-90 ibritumomab tiuxetan plus busulfan, cyclophosphamide, and etoposide (BuCyE) versus BuCyE alone as a conditioning regimen for non-Hodgkin lymphoma

Background Radioimmunotherapy agents have a highly significant role in autologous stem cell transplantation as they improve tolerability and increase the efficacy of the conditioning regimen. Methods We retrospectively analyzed the efficacy and toxicity of yttrium-90 ibritumomab tiuxetan (Zevalin) combined with intravenous busulfan, cyclophosphamide, and etoposide (Z-BuCyE) compared with those of BuCyE alone followed by autologous stem cell transplantation in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL). The efficacy, toxicity, and engraftment characteristics were compared between 19 patients who received Z-BuCyE and 19 historical controls who received BuCyE. Results The 2 treatment groups shared similar baseline characteristics. The median time to platelet engraftment (>20×109/L) and neutrophil engraftment (>0.5×109/L) did not significantly differ between the Z-BuCyE group (12 days and 10 days, respectively) and the BuCyE group (12 days and 10 days, respectively). No significant differences were observed between the groups with respect to toxicities and treatment-related mortality. The median follow-up period was 30.4 months, and median event-free survival was generally better in the Z-BuCyE group (12.5 months) vs. the BuCyE group (6.2 months, P=0.236). No significant difference in overall survival between the groups was noted. Conclusion Adding ibritumomab tiuxetan to BuCyE high-dose chemotherapy may benefit patients with relapsed or refractory B-cell NHL with no risk of additional toxicity.

Adjuvant chemotherapy for elderly patients (aged 70 or older) with gastric cancer after a gastrectomy with D2 dissection: A single center experience in Korea.

Adjuvant chemotherapy is recommended for gastric cancer after a gastrectomy with D2 dissection. However, its survival benefit in elderly patients is unclear. Here we investigated the use of adjuvant chemotherapy in patients ≥70 years old with stage II or III gastric cancer.