Moon Ki Choi

Safety and efficacy of gemcitabine or pemetrexed in combination with a platinum in patients with non-small-cell lung cancer and prior interstitial lung disease.

AbstractPurposenThe incidence of lung cancer in patients with interstitial lung disease (ILD) is higher than in the general population; however, the clinical benefit of chemotherapy and the appropriate regimen for non-small-cell lung cancer (NSCLC) patients with ILD remain unclear. This study was conducted to elucidate the safety and efficacy of palliative chemotherapy with gemcitabine or pemetrexed, both in combination with a platinum agent in NSCLC patients with ILD.Patients and methodsPatients with advanced or recurrent NSCLC and ILD who received gemcitabine or pemetrexed in combination with a platinum agent as first-line chemotherapy were retrospectively analyzed. Clinical outcomes, including response rate, overall survival (OS), and progression-free survival (PFS), in addition to the acute exacerbation of ILD after chemotherapy were investigated.ResultsBetween January 2007 and December 2011, 52 patients were analyzed. The median age at chemotherapy was 67. Thirty-two patients (61.5xa0%) had adenocarcinoma histology. With respect to the types of ILD, idiopathic interstitial pneumonia (IIP) and non-IIP were observed in 42 (80.8xa0%) and 10 (19.2xa0%) patients, respectively. The FEV1 level was less than 80xa0% of the predicted value in 15 of the 41 patients in whom it was measured. The overall response rate was 42.3xa0% (95xa0% CI 28.8–55.9), and the median PFS was 5.4xa0months (95xa0% CI 4.6–6.2). The median OS was 7.9xa0months (95xa0% CI 5.5–10.3), and the 1-year survival rate was 31.7xa0% (95xa0% CI 19.0–44.4). Eight patients (15.4xa0%) died within 3xa0months of first-line chemotherapy. Multivariate analysis demonstrated that a heavy smoking history (40 or more pack-year smoking history) was an independent adverse prognostic factor for OS. An acute exacerbation of ILD (AE-ILD) caused by first-line chemotherapy was noted in 5.8xa0% of patients.ConclusionOur results suggest that gemcitabine or pemetrexed in combination with platinum agents could be a feasible option for advanced NSCLC with ILD with some risk of AE-ILD or early death. To establish the efficacy of palliative chemotherapy for patients with NSCLC and ILD, further well-controlled prospective studies are needed.

Treatment outcome of adult patients with Burkitt lymphoma: results using the LMB protocol in Korea

Burkitt lymphoma (BL) is a rare subtype of adult non-Hodgkin lymphoma, so studies on the outcome of adult BL, especially in Asian patients, are scarce. We report our results using the LMB protocol on Korean adult BL patients. Thirty-eight newly diagnosed BL patients were treated with the LMB protocol; 29 males and nine females with a median age of 47xa0years (range 18–70) were analyzed, and 14 (36.8%) patients had central nervous system or bone marrow involvement. After the induction phase, 28 patients achieved complete response (CR, 73.7%) and five showed partial response (PR, 13.2%). Among those achieving CR, only four showed relapse. All of the non-CR patients died, including five PR and one with progressive disease. The other four patients died because of infection after the first course of induction. The progression-free and overall estimated survival at 5xa0years was 74.99% and 68.10%, respectively. Of the 12 patients who died, the median survival was 4.43xa0months (95% confidence interval 1.43–7.43xa0months). Thus, most deaths occurred shortly after diagnosis, and four patients older than 58xa0years died after the first induction cycle. Most early deaths were caused by treatment-related morbidity and failure to achieve complete response. B symptoms, advanced age, bone marrow involvement, and St. Jude/Murphy stage IV classification were significantly associated with poor overall survival. In conclusion, the LMB protocol was effective for Korean adult BL patients. However, considering the high incidence of treatment-related deaths and the poor outcome of non-CR patients, risk-adapted modification of the induction phase is warranted.

Clinical implications of esophagorespiratory fistulae in patients with esophageal squamous cell carcinoma (SCCA)

In this retrospective study, we investigated the incidence of esophagorespiratory fistula (ERF) in esophageal squamous cell carcinomas, clinical characteristics and outcomes of esophageal cancer patient with ERF, and effective therapeutic options. From 1998 to 2007, 1,095 patients with squamous cell carcinomas of the esophagus were treated at Samsung Medical Center. A comprehensive retrospective review of all these patients with clinical data of ERF was performed. The incidence of ERF in patients with esophageal cancer was 4.7% (52/1095). Comparing with the patients without ERF, the patients with ERF presented with a more advanced stage of disease, more frequent involvement of upper-mid thoracic esophagus, a longer segment of the tumor, and more initial airway involvement. The median time from the diagnosis of esophageal cancer to the development of a fistula was 7.9 months. ERF could be divided into three different categories according to the causes; (1) ERF associated with complication of the cancer progression (65.4%), (2) ERF related with treatments (28.8%), (3) ERF with mixed causes (5.8%). Four patients (8%) received radiation therapy, and nine patients (17%) underwent surgery to treat the ERF. Many of the patients with ERF were palliated with esophageal stent (40%) and/or gastrostomy (38%). The median survival time after diagnosis of the ERF was 8.0 weeks. An ERF resulting from esophageal cancer entails a poor prognosis in spite of supportive and/or definitive treatment. More comprehensive approach to improve the course of ERF and active supportive care, which can prevent complication from leakage, should be developed.

Phase I study of intraperitoneal irinotecan in patients with gastric adenocarcinoma with peritoneal seeding

PurposeThe objectives of this phase I study were to determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs), and preliminary efficacy of intraperitoneally administered irinotecan (CPT-11) in gastric cancer patients with peritoneal seeding.Experimental designGastric adenocarcinoma patients with surgical biopsy proven peritoneal seeding were enrolled at the time of surgery. Prior to IP chemotherapy, patients underwent palliative gastrectomy and CAPD catheter insertion in which CPT-11 was administered on postoperative day 1. The IP CPT-11 was initiated at 50xa0mg/m2, which was escalated to 100, 150, 200, 250, and 300xa0mg/m2. IP CPT-11 chemotherapy was repeated every 3xa0weeks.ResultsSeventeen patients received a total of 56xa0cycles at five different CPT-11 dose levels. The DLTs were neutropenic fever, neutropenia, and diarrhea. At the dose level 2 (100xa0mg/m2), there were one DLTs in one of the first cohort of three patients, but no DLTs at the second cohort of this level. At the dose level 5 (250xa0mg/m2), two DLTs were detected in the first two patients; thus, the accrual was stopped resulting in the recommended dose of IP CPT-11 of 200xa0mg/m2. Median progression-free survival was 8.6xa0months (95% CI, 5.9,11.2), and median overall survival was 15.6xa0months (95% CI, 8.4,22.8). Pharmacokinetic results of the study showed that the Cmax of peritoneal SN-38 was achieved earlier than that of plasma SN-38.ConclusionsIntraperitoneally administered CPT-11 was feasible and tolerable. Further, phase II study of IP CPT-11 in gastric cancer patients with peritoneal seeding is warranted.

Prognostic relevance of biological subtype overrides that of TNM staging in breast cancer: discordance between stage and biology.

Recently, we faced difficult treatment decisions regarding appropriate adjuvant systemic treatment, especially for patients who show discordance between stage and tumor biology. The aim of this study was to compare the prognostic relevance of the TNM staging system with that of intrinsic subtype in breast cancer. We retrospectively identified women patients who received curative surgery for stage I–III breast cancer with available data on immunohistochemistry profiles including hormone receptor (HR) status, human epidermal growth factor receptor 2 (HER2) status, and Ki 67 staining at the Samsung Medical Center from January 2004 to September 2008. Primary outcomes were recurrence-free survival (RFS) and overall survival (OS). A total of 1145 patients were diagnosed with breast cancer and received curative surgery. Of these, 463 (40.4xa0%) patients were stage I, and 682 (59.6xa0%) were stage II or III. In addition, 701 (61.2xa0%) patients were HR positive, 239 (20.9xa0%) were HER2 positive, and 205 (20.9xa0%) had triple-negative breast cancer. The 5-year RFS for the patients who were HR positive and HER2 negative with a low Ki 67 staining score (0–25xa0%) was 99xa0%. The 5-year RFS for patients who were HER2-positive or had triple-negative breast cancer were 89 and 83xa0%, respectively (P valueu2009=u2009<0.001). In multivariate analysis, advanced stage (II/III) and unfavorable biology (HER2 positive or triple negative) retained their statistical significance as predictors of decreased RFS and OS. Patients with advanced-stage disease (II or III) but favorable tumor biology (HR positive and HER2 negative and low Ki 67) had better clinical outcomes than those with stage I disease and unfavorable tumor biology in terms of RFS (99 versus 92xa0%, P valueu2009=u20090.011) and OS (99 versus 96xa0%, P valueu2009=u20090.03) at 5xa0years. The current results showed that intrinsic subtype has a greater prognostic impact in predicting clinical outcomes in subpopulations of patients with stage I–III breast cancer who show discordance between stage and biologic subtypes.

Treatment outcome of relapsed/refractory primary central nervous system diffuse large B-cell lymphoma: a single-center experience of autologous stem cell transplantation.

No salvage treatment strategy has been established for relapsed or refractory primary central nervous system lymphoma (PCNSL). We compared treatment outcomes of patients who underwent salvage chemotherapy with or without autologous stem cell transplantation (ASCT). We retrospectively analyzed PCNSL patients who were histologically diagnosed with diffuse large B-cell lymphoma. All patients relapsed after high-dose methotrexate (MTX)-based chemotherapy, or were refractory to high-dose MTX. Patients were treated with salvage chemotherapy, such as ICE/D (ifosfamide, carboplatin, etoposide, and dexamethasone) or high-dose MTX. High-dose chemotherapy containing thiotepa and busulfan followed by ASCT was performed if patients were eligible for ASCT after salvage treatment. Forty-five patients (35 relapsed and 10 refractory) received ICE/D or high-dose MTX. Despite the important difference that ICE/D was used predominantly for early relapsed or refractory patients, the two salvage treatments produced similar overall response rates [84.4xa0% (38/45) for ICE/D and 81.3xa0% (13/16) for high-dose MTX re-treatment]. Eighteen patients underwent ASCT, whereas 27 patients received salvage chemotherapy alone. The median progression-free survival of patients who underwent ASCT (19.5xa0months) was significantly better than that of patients who did not receive ASCT (6.7xa0months, Pxa0=xa00.023). Multivariate analysis showed that refractoriness to initial treatment and no ASCT were significantly associated with poor survival outcome. Our study suggested that the combination of ifosfamide, carboplatin, etoposide, and dexamethasone may represent a feasible salvage treatment option for relapsed or refractory PCNSL, and that high-dose chemotherapy containing thiotepa and busulfan followed by ASCT may be effective for patients with a favorable toxicity profile.

Is there any predictor for clinical outcome in EGFR mutant NSCLC patients treated with EGFR TKIs

BackgroundTyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) have demonstrated some dramatic response rate and prolonged progression-free survival (PFS) in advanced non-small-cell lung cancer (NSCLC) patients with activating EGFR mutation. However, PFS and overall survival (OS) among those patients who were treated with EGFR TKIs are inconsistent and unpredictable. In this study, we evaluated predictors of clinical outcome in EGFR mutant NSCLC patients treated with EGFR TKIs.MethodsA total of 148 patients who had metastatic or recurrent NSCLC with activating EGFR mutation treated with either erlotinib or gefitinib as a first-line (nxa0=xa010) and a second-line or more treatment (nxa0=xa0138) were retrospectively reviewed.ResultsThe median follow-up duration was 21.9xa0months (range, 1.1–62.5). The median PFS and OS for a total 148 patients were 10.6xa0months (95xa0% CI 9.0–12.2) and 21.8xa0months (95xa0% CI 18.5–25.1), respectively. The survival outcomes were similar between the first-line and second-line or more line of treatment of EGFR TKIs (Pxa0=xa00.512 for PFS, Pxa0=xa00.699 for OS). Although a high number of metastasis sites (3–6 vs. 1–2) were associated with shorter PFS and OS (median PFS 9.9 vs. 11.9xa0months, Pxa0=xa00.019; median OS 16.4 vs. 22.2xa0months, Pxa0=xa00.021, respectively) in univariate analysis, but not in multivariate analysis. According to the clinical and molecular markers by multivariate analysis, there were no significant differences in PFS. When PFS was dichotomized by median 11xa0months for 105 patients treated with EGFR TKIs as second-line therapy, no significant differences in any clinical or molecular features were found between longer PFS and shorter PFS groups.ConclusionsDespite the inconsistencies in PFS among EGFR mutant patients treated with EGFR TKIs, no significant differences of clinical features were noted, thereby suggesting a need for more understanding of the heterogeneity of underlying biology.

Prognostic and predictive value of metabolic tumor volume on 18 F-FDG PET/CT in advanced biliary tract cancer treated with gemcitabine/oxaliplatin with or without erlotinib

This study aimed to evaluate the prognostic significance and predictive performance of volume-based parameter of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in biliary tract cancer (BTC). Of the 268 patients who were enrolled onto phase III gemcitabine/oxaliplatin (GEMOX) versus GEMOX/erlotinib trial, a total of 48 patients had pretreatment 18F-FDG PET/CT available for analysis. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis for the primary tumor were measured. The prognostic significance of these parameters and clinicopathological variables was assessed by Cox proportional hazards regression analysis. A cutoff of 98.8xa0ml for the MTVliver was the best discriminative value for predicting overall survival (>9xa0months). Multivariate analyses with adjustments for age, performance status, and disease status showed that only MTVliver was an independent prognostic factor associated with overall survival (HR 2.149, 95xa0% CI 1.124–4.109, Pxa0=xa00.021). SUVmax did not show any correlation with overall survival. For patients in the high-MTVMBP group, overall survival was longer in the chemotherapy plus erlotinib group than in the chemotherapy-alone group [median 8.3xa0months (5.5–11.1) vs. 4.0xa0months (0.0–8.0); Pxa0=xa00.048]. MTV may be considered as a significant independent metabolic prognostic factor for overall survival in patients with BTC and predictive marker for the selection of patients for the addition of erlotinib to first-line chemotherapy.

Population pharmacokinetics of CPT-11 (irinotecan) in gastric cancer patients with peritoneal seeding after its intraperitoneal administration

PurposeIt is well known that CPT-11 (irinotecan) is biotransformed to its active metabolite, SN-38, by carboxylesterase in the liver and other tissues. However, little is known about its pharmacokinetics (PK) when administered intraperitoneally. The aim of our study was to develop a population pharmacokinetic model for CPT-11 and SN-38 following the intraperitoneal (IP) administration of CPT-11.MethodsPharmacokinetic data obtained from 16 gastric adenocarcinoma patients with peritoneal seeding were used. Administered doses ranged from 50 to 250xa0mg/m2. To measure CPT-11 and SN-38 levels, we collected samples of peritoneal fluid, plasma and urine 0, 0.5, 1.5, 2, 3.5, 8, 12, 25.5, 49 and 56 h after IP infusion. Several multicompartmental pharmacokinetic models were tested for CPT-11 and SN-38 in the sampled peritoneal fluid, plasma and urine. NONMEM ver. 6 was used throughout the model-building process.ResultsPeak concentrations were achieved earlier for peritoneal SN-38 than for plasma SN-38. The apparent metabolic clearance of peritoneal and plasma CPT-11 to peritoneal and plasma SN-38 accounted for 0.2 and 7.3% of the total clearance of peritoneal and plasma CPT-11, respectively. The typical values of steady-state volume of distribution (Vss) (46.6xa0L/m2), inter-compartment clearance (6.70xa0L/h/m2) and clearance (16.0xa0L/h/m2) for plasma CPT-11 were estimated in a two-compartment PK model.ConclusionsOur results demonstrate that a small fraction of intraperitoneally administered CPT-11 was metabolized in situ to active SN-38 and that the Vss of plasma CPT-11 following IP administration in our patient cohort was lower than that estimated in previous reports following the intravenous administration of CPT-11.

Clinical features and treatment outcomes of primary cutaneous B-cell lymphoma: a single-center analysis in South Korea

Clinical features and treatment outcomes of primary cutaneous B-cell lymphoma (PCBCL) have rarely been reviewed, due to the rarity and pathologic obscurity of this disease. We reviewed 21 patients who were pathologically diagnosed with PCBCL from Samsung Medical Center’s lymphoma cohort, following the WHO–EORTC classification system: primary cutaneous follicle-center lymphoma (PCFCL), primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL, LT), and cutaneous diffuse large B-cell lymphoma, other (PCDLBCL, other). Of 2831 B-cell lymphoma cases, PCBCL comprised only 0.74xa0% of cases (Nxa0=xa021, eight PCLBCL, LT (0.28xa0%), 10 PCMZL (0.35xa0%), two PCDLBCL, other (0.06xa0%), and one PCFCL (0.03xa0%)). Eighteen of 21 patients received treatment for PCBCL (12 chemotherapy alone, three radiotherapy alone, three chemotherapy following radiotherapy) and complete response (CR) was observed in 17 patients. The median progression-free survival was 44xa0months [95xa0% confidence interval (CI): 11–61xa0months]. Two patients had died at the time of analysis, with a median follow-up duration of 85xa0months [95xa0% confidence interval (CI): 55–118xa0months]. PCBCL cases in this study have a higher proportion of disseminated PCMZL and PCLBCL, LT, and excellent outcomes were observed with chemotherapy, including R-CHOP or R-CVP irrespective of staging and pathologic subtype.