Jung Hun Kang

Salvage Chemotherapy for Pretreated Gastric Cancer: A Randomized Phase III Trial Comparing Chemotherapy Plus Best Supportive Care With Best Supportive Care Alone

PURPOSEnWhen designing this trial, there was no evidence that salvage chemotherapy (SLC) in advanced gastric cancer (AGC) resulted in substantial prolongation of survival when compared with best supportive care (BSC). However, SLC is often offered to pretreated patients with AGC for anecdotal reasons.nnnPATIENTS AND METHODSnPatients with AGC with one or two prior chemotherapy regimens involving both fluoropyrimidines and platinum and with an Eastern Cooperative Oncology Group performance status (PS) 0 or 1 were randomly assigned in a ratio of 2:1 to SLC plus BSC or BSC alone. Choice of SLC-either docetaxel 60 mg/m(2) every 3 weeks or irinotecan 150 mg/m(2) every 2 weeks-was left to the discretion of investigators. Primary end point was overall survival (OS).nnnRESULTSnMedian OS was 5.3 months among 133 patients in the SLC arm and 3.8 months among 69 patients in the BSC arm (hazard ratio, 0.657; 95% CI, 0.485 to 0.891; one-sided P = .007). OS benefit for SLC was consistent in most of the prospectively defined subgroups, including age, PS, number of prior treatments, metastatic sites, hemoglobin levels, and response to prior chemotherapy. SLC was generally well tolerated, and adverse events were similar in the SLC and BSC arms. We found no median OS difference between docetaxel and irinotecan (5.2 v 6.5 months; P = .116).nnnCONCLUSIONnTo our knowledge, this is the largest phase III trial comparing SLC plus BSC with BSC alone in AGC. In pretreated patients, SLC is tolerated and significantly improves OS when added to BSC.

Phase II study of second line gemcitabine single chemotherapy for biliary tract cancer patients with 5-fluorouracil refractoriness

SummaryAim We conducted this phase II study in an effort to evaluate the efficacy and safety of a gemcitabine single chemotherapy as a second-line treatment for biliary tract cancer (BTC) patients who evidenced disease progression after the administration of 5-fluorouracil (5-FU)-based palliative chemotherapy. Patients and Method Patients treated previously with 5-FU-based palliative treatment as a BTC were enrolled in this study. Treatment consisted of gemcitabine at a dosage of 1,250xa0mg/m2 administered intravenously over a 30-minute period on days 1 and 8 of each 21-day cycle until progression. Results Between Feb. 2006 and July 2009, a total of 32 patients were assigned to treatment groups. 16 patients (50%) had cancers of intra-hepatic cholangiocarcinoma, 12 patients (37.5%) had gall bladder cancer, and 4 patients (12.5%) had extra-hepatic cholangiocarcinoma. In the 29 patients whose tumor responses were evaluated, two achieved a partial response, with an overall response rate of 6.9% (95% confidence interval [CI]: 0.0–16.7%). Six patients (20.7%) evidenced stable disease and 21 patients (72.4%) evidenced progression during the course of treatment. The median follow-up duration was 23.2xa0months (range: 3.0–53.1xa0months). The median time to progression (TTP) was 1.6xa0months (95% CI: 1.3–1.9xa0months), and the median overall survival (OS) time was 4.1xa0months (95% CI: 2.7–5.5xa0months). Poor performance status (ECOG 2) in patients was predictive of shorter TTP. Lower albumin levels (<3.5xa0g/dL) in patients were predictive of shorter TTP and OS. Conclusions Despite first salvage chemotherapy in the phase II study for patients with 5-FU refractory BTC, the results in terms of RR, TTP, and OS were lower than expected. However, selected patients with good performance status and sufficient albumin levels may have derived some survival benefits from salvage chemotherapy.

A Phase II Study of Irinotecan, Continuous 5-Fluorouracil, and Leucovorin (FOLFIRI) Combination Chemotherapy for Patients With Recurrent or Metastatic Gastric Cancer Previously Treated With a Fluoropyrimidine-Based Regimen

Objectives:A phase II study was carried out to assess the efficacy and toxicity of combination chemotherapy with irinotecan, 5-fluorouracil (5-FU), and leucovorin (FOLFIRI) for the treatment of patients with metastatic or recurring gastric cancer previously treated with fluoropyrimidine-based chemotherapy. Methods:Eligible patients were those who had metastatic gastric cancer previously treated with a fluoropyrimidine-based chemotherapy regimen or had disease recurrence within 6 months of completing adjuvant fluoropyrimidine-containing chemotherapy. Participants received irinotecan (150 mg/m2 on day 1) and leucovorin (LV; 20 mg/m2 on days 1–2) followed by continuous infusion of 5-FU (1500 mg/m2 on days 1–2), every 2 weeks. Results:Between April 2006 and March 2008, 33 patients were enrolled in the study. FOLFIRI served as a second-line treatment in 27 patients, third-line treatment in 4 patients, and fourth-line treatment in 2 patients. The patients had a median age of 60 years (range, 40–75) and underwent 132 cycles of chemotherapy, with a median of 3 cycles (range, 1–15) per patient. The response rate was 18.2%, and the disease control rate was 36%. Median overall survival was 5.1 months (95% confidence interval, 3.74–6.45), and median time to progression was 2.3 months (95% confidence interval, 1.81–2.78). The major grade 3–4 toxicity was neutropenia (45.4%). Conclusion:Combination chemotherapy with irinotecan, 5-FU, and LV is feasible in gastric cancer patients previously treated with fluoropyrimidine-based chemotherapy.

Pilot study of irinotecan/oxalipltin (IROX) combination chemotherapy for patients with gemcitabine- and 5-fluorouracil- refractory pancreatic cancer.

SummaryBackground Gemcitabine- and 5-fluorouracil (5-FU)- based chemotherapy is a commonly used adjuvant or palliative treatment for patients with pancreatic cancer. However, a standard chemotherapy regimen has yet to be developed for patients refractory to gemcitabine and 5-FU treatment. We attempted to evaluate the efficacy and safety of a combination of irinotecan and oxaliplatin (IROX) as a salvage treatment for patients with gemcitabine- and 5-FU- refractory pancreatic cancer. Patients and Methods Patients with advanced pancreatic cancer who were refractory to prior gemcitabine- and 5-FU- based chemotherapy were enrolled in this study. IROX chemotherapy was administered as follows: Irinotecan, 150xa0mg/m2 on day 1; and oxaliplatin, 85xa0mg/m2 on day 1 over 90xa0min every 2xa0weeks. Result From Mar. 2006 to Dec. 2008, a total of 14 patients were administered 50 cycles of chemotherapy. The male-to-female ratio of the patient group was 11:3. These patients ranged in age from 48 to 73xa0years (median 65.5xa0years old). 3 patients (21.4%) evidenced partial responses. four patients (28.6%) exhibited stable disease. The median time to progression and overall survival time were 1.4 (95% CI: 1.2–1.6) months and 4.1 (95% CI: 2.0–6.2) months, respectively. Major hematologic toxicities included grade 1–2 anemia (88%), neutropenia (36%), thrombocytopenia (30%), and grade 3–4 neutropenia (10%). The most frequently detected non-hematological toxicities were grade 3 diarrheas (14%). Conclusion The IROX regimen appears to constitute a feasible and tolerable salvage therapy in patients with advanced pancreatic cancer who have been previously treated with gemcitabine- and 5-FU-based chemotherapy.

A phase II study of S-1 and oxaliplatin (SOx) combination chemotherapy as a first-line therapy for patients with advanced gastric cancer

SummaryBackground Palliative chemotherapy has been shown to have a survival benefit for patients with recurrent or metastatic gastric cancer. 5-fluorouracil (5-FU) and cisplatin have been widely used in a variety of combinations. We conducted a phase II study of combination chemotherapy with new agents, S-1 and oxaliplatin (SOx), in advanced gastric cancer patients in an effort to evaluate the efficacy and toxicity of this regimen. Method Histologically confirmed recurrent or metastatic gastric cancer were treated by the oral administration of S-1 80xa0mg/m2/day on days 1–28, and oxaliplatin 85xa0mg/m2 administered as a 90-min intravenous infusion on days 1, 15, and 29. Treatment courses were repeated every 6xa0weeks. Patients received a maximum of four cycles. Results From Feb 2006 to May 2008, 41 patients were enrolled in this study. The ratio of males to females was 28 to 13. The median patient age was 61xa0years (range, 36–74xa0years), and 85.4% (35/41) of the patients had a performance status (ECOG) of 1. The median number of chemotherapy cycles administered was 3 (range, 1–4). According to the results of our Intent-to-Treat analysis, 22 patients (53.7%) achieved a partial response (95% CI, 38–70%). 15 patients (36.6%) evidenced a stable disease, and 1 patient (2.4%) progressed during the course of the treatment. 3 patients were lost to follow-up prior to evaluation. The median time to progression and overall survival time were 4.6xa0months (95% CI, 3.4–5.8xa0months) and 7.8xa0months (95% CI, 6.9–8.7xa0months) from the start of the chemotherapy, respectively. A total of 114 cycles were assessed for toxicity. The major hematologic toxicities included grade 2 anemia (41.2%), grade 1-2 neutropenia (28.1%), and grade 1 thrombocytopenia (23.7%). Only 1 cycle of neutropenic fever occurred. The non-hematological toxicities observed were grade 3 vomiting (12.2%) and grade 3 diarrhea (4.9%). No treatment-related deaths occurred in our patient population during the study period. Conclusion The SOx regimen evidenced a relatively high response rate and was well tolerated as a first-line therapy for advanced gastric cancer.

D-Dimer Can Serve as a Prognostic and Predictive Biomarker for Metastatic Gastric Cancer Treated by Chemotherapy

Abstract Systemic activation of hemostasis and thrombosis has been implicated in tumor progression and metastasis. D-dimer has been used as an indicator for the thrombosis. Here, we investigated the role of the activation of coagulation in patients with metastatic gastric cancer by measuring D-dimer level. We conducted an observation study of 46 metastatic gastric cancer patients who received palliative chemotherapy (CTx). D-dimer levels were assessed before CTx and at the first response evaluation after CTx. The overall survival (OS) of patients with pretreatment D-dimer levels <1.5u200a&mgr;g/mL was significantly longer than that of patients with D-dimer levels ≥1.5u200a&mgr;g/mL (22.0 vs 7.9 months, Pu200a=u200a0.019). At the first response evaluation, the mean level of D-dimer was significantly decreased by 2.11u200a&mgr;g/mL in patients either with partial response or stable disease (Pu200a=u200a0.011) whereas the mean level of D-dimer, although the difference did not reach statistical significance, was increased by 2.46u200a&mgr;g/mL in patients with progressive disease. In addition, the OS of patients with D-dimer levels <1.0u200a&mgr;g/mL at the first response evaluation was significantly longer than that of patients with D-dimer levels ≥1.0u200a&mgr;g/mL (22.0 vs 7.0 months, Pu200a=u200a0.009). The lower D-dimer levels (<1.0u200a&mgr;g/mL) at the first response evaluation after CTx was independent predictive factor for better survival in multivariate analysis (Pu200a=u200a0.037). This study suggests that D-dimer levels may serve as a biomarker for response to CTx and OS in patients with metastatic gastric cancer.

Epstein-Barr Virus -Positivity in Tumor has no Correlation with the Clinical Outcomes of Patients with Angioimmunoblastic T-cell Lymphoma

Background/Aims Epstein-Barr virus (EBV) is involved in the pathogenesis of angioimmunoblastic T-cell lymphoma (AILT), but its precise role and prognostic impact are not clear. This study aimed to evaluate the incidence of EBV-postitivity in the tumor and bone marrow (BM) samples from AILT patients, and their correlations with the clinical variables and patient survival. Methods Seventy AILT cases were identified over a period of 8 years. Twenty seven cases were investigated for their EBV tumor status, and 10 BM samples of these patients were investigated for their EBV status with using in situ hybridization (ISH). EBV PCR was performed for the BM mononuclear cells in 8 cases. Results Among the 27 tumor specimens, ten (37%) were EBV-positive. Only CD20-negativity in tumor correlated with the EBV-positivity (p=0.035). In 13 (48%) patients, gross tumor involvement was recognized by hematoxylin-eosin staining at the time of diagnosis. Among the 10 patients who had additional BM slides available, there were 3 with BM involvement, and none showed EBV positive results on ISH. EBV PCR of the BM mononuclear cells revealed one-positive case among 8 patients. This patient was negative for both BM involvement and EBV ISH. The median overall survival of the 25 treated patients was 48.9 months (95% CI: 18.6~79.2 months). Neither overall survival nor progression-free survival was related with EBV-positivity of the tumor. Conclusions EBV-positivity of tumor had no impact on the prognosis of AILT patients.

CHOP followed by involved field radiotherapy for localized primary gastric diffuse large B-cell lymphoma: Results of a multi center phase II study and quality of life evaluation

We aimed to define the role of cyclophosphamide, vincristine, doxorubicin, prednisone (CHOP) followed by involved field radiotherapy (IFRT) for treating localized primary gastric diffuse large B-cell lymphoma (DLBCL). Newly diagnosed patients with localized primary gastric DLBCL were to receive four cycles of CHOP followed by IFRT of 40.0 Gy. At 1 year after the completion of treatment, patients filled out the EORTC Quality of Life Questionnaire specified for stomach cancer (QLQ-C30-STO22). Fifty evaluable patients (25 men, 25 women) were included. The median age was 54.5 years (range, 21 – 73 years. The overall response rate to the CHOP was 94% (95% confidence interval [CI], 87 – 100) in the intent-to-treat population. Forty-one of the 50 patients (82%; 95% CI, 71 – 93) achieved complete remission (CR). After the completion of radiotherapy, five patients who were in PR following chemotherapy eventually attained CR. The overall complete response rate was thus 92% (95% confidence interval, 84 – 99). With a median follow-up period of 30 months, the 2-year progression-free and overall survival rate was 92% and 92%, respectively. The gastric function was well preserved with negligible stomach-related symptoms at 1 year after the completion of treatment. This organ-preserving combined treatment is highly effective and well tolerated for the patients with localized gastric DLBCL.

Retrospective analysis of extra-gastrointestinal stromal tumors.

AIMnTo investigate the clinicopathologic features of patients with extra-gastrointestinal stromal tumors (EGISTs) in South Korea.nnnMETHODSnA total of 51 patients with an EGIST were identified. The clinicopathologic features, including sex, age, location, tumor size, histology, mitotic rate, immunohistochemical features, genetic status and survival data, were analyzed.nnnRESULTSnThe median age was 55 years (range: 29-80 years), and male:female ratio was 1:1.04. The most common site was in the mesentery (n = 15) followed by the retroperitoneum (n = 13) and omentum (n = 8). The median tumor size was 9.0 cm (range: 2.6-30.0 cm) and the median mitotic rate was 5.0/50HPF. (1/50 - 185/50). KIT was analyzed in 16, which revealed 10 cases with wild-type KIT and 6 cases with an exon 11 mutation. Among 51 patients, 31 patients had undergone surgery, and 10 had unresectable disease and had taken palliative imatinib, which resulted in 22.7 mo of progression-free survival. Of the patients who had undergone surgery, 18 did not take adjuvant imatinib, and 8 of these were categorized as high risk according to the risk criteria. However, the relapse-free survival was not different (P = 0.157) between two groups.nnnCONCLUSIONnBecause the biologic behaviors of GISTs differ according to the location of the tumor, a more stratified strategy is required for managing EGISTs including incorporation of molecular features.

IMVP-16/Pd followed by high-dose chemotherapy and autologous stem cell transplantation as a salvage therapy for refractory or relapsed peripheral T-cell lymphomas

The present study aimed to analyse the treatment outcome of IMVP-16/Pd (ifosfamide, methotrexate, etoposide and prednisone) followed by high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) for patients with peripheral T-cell lymphomas (PTCLs) who were previously treated with CHOP. Since 1995, 32 PTCL patients were treated with IMPV-16/Pd. Nine of 32 patients achieved a response (5 demonstrating complete response (CR) and 4 partial response), with an overall response rate of 28.1% (95% onfidence interval 0.12–0.45). Considering histopathologic subtypes, 3 of 4 relapsed natural killer (NK)/T-cell lymphoma patients (75%) achieved CR, but only 1 of 6 in non-NK/T-cell lymphoma patients (16.7%) achieved CR (P = 0.19). Six of 9 IMVP-16/Pd sensitive patients underwent HDC/ASCT. Three of them relapsed after 3, 4 and 15 months, respectively, of HDC/ASCT. Estimated 3-year overall survival and progression-free survival rates were 14.2% and 12.2%, respectively. Multivariate analysis revealed that responsiveness to first-line CHOP was a significant prognostic factor (P < 0.05). These results indicate that IMVP-16/Pd followed by HDC/ASCT appears to be an effective salvage regimen, especially for NK/T-cell lymphoma.