Publications (50) View all
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Article: A Trial of Autologous Ex vivo-expanded NK Cell-enriched Lymphocytes with Docetaxel in Patients with Advanced Non-small Cell Lung Cancer as Second- or Third-line Treatment: Phase IIa Study.
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ABSTRACT: New strategies are still needed to enhance the treatment outcome for advanced non-small cell lung cancer, in spite of recent remarkable developments. Cancer immunotherapy has been attractive since a long time, with diverse clinical attempts and results. In particular, natural killer (NK) cells have received considerable attention because of their potential role in immune surveillance in vivo by destroying infected or transformed cells. Major histocompatibility complex class I-related chain A/B (MICA/B) on tumor cells, known as the representative ligand for NKG2D receptor on NK cells, has been reported to be modulated by a variety of stress factors, including some chemotherapeutic agents, and it is anticipated that enhancing MICA/B expression will be contributory to anticancer treatment. With recent development of expanding autologous ex vivo NK cell-enriched lymphocytes (NKL), we designed a trial to augment the anticancer effect by co-administering NKL and docetaxel, one of the second-line agents used for treatment of patients with advanced non-small cell lung cancer (NSCLC). Eligible patients were between the age of 20 and 75 years, with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2, and previously received one chemotherapy or two regimens including one epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, stage IIIB/IV, histologically- or cytologically-proven NSCLC with measurable lesions. NKL were kindly prepared and provided from NKBIO Co. (Seongnam City, Korea). Feasibility, adverse effects, progression-free survival (PFS) were evaluated and compared with the historical control of weekly docetaxel regimen. Nineteen patients were enrolled before early closure. NKL production and administration were feasible in all cases, even in those with disseminated disease. No additional adverse events were observed in addition to those reported for docetaxel-alone. PFS of 3 months and 10.5% response rate (RR), with two cases of partial response, were observed and were similar to the historical control (PFS=2.9 months, RR=8.0%). To our knowledge, this is the first report on the combination of NKL with docetaxel in patients with advanced NSCLC. Autologous NKL production and co-administration with docetaxel were feasible without further toxicity or complication. Benefit in PFS and RR, as compared with the historical control, was not detected in this study population with advanced NSCLC. In order to determine whether the combination of NKL and chemotherapy has any anticancer effect, an additional study should be performed in patients with low tumor burden, such as those with less advanced disease or those in remission.Anticancer research 05/2013; 33(5):2115-22. · 1.73 Impact Factor -
Article: Adjuvant Postoperative Radiotherapy with or without Chemotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck: The Importance of Patient Selection for the Postoperative Chemoradiotherapy.
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ABSTRACT: We wanted to evaluate the role of postoperative chemoradiotherapy (CRT) for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). From March 1993 to July 2008, 101 patients with advanced SCCHN and who had undergone macroscopically complete resection were enrolled. Survival and the cumulative incidence of local or regional relapse, metastasis, and acute toxicity were analyzed. There was a marginally significant difference of disease-free survival at five years in favor of the CRT arm (51.3% vs. 41.8%, respectively; p=0.10). However, there was no significant difference in overall survival between the two treatment arms (p=0.20). The rate of locoregional failure only for the radiotherapy arm was significantly higher than that for the CRT arm (23.2% vs. 4.4%, respectively; p=0.01). The incidence of grade 3 or 4 hematologic toxicity was significantly higher in the CRT arm than that in the radiotherapy arm (37.7% vs. 1.7%, respectively; p=0.01). In CRT arm, early mortality group within 1 year had low performance status and old age over sixty compared with those of the others. After curative-intent surgery, adjuvant CRT is more effective in locoregional tumor control than radiotherapy alone for patients with advanced SCCHN. However, compared with radiotherapy alone, this combined modality treatment had no survival benefit, and was significantly associated with increased toxicity. Thus, patients with low performance status and old age must be cautious in selection of toxic trimodality treatment.Cancer Research and Treatment 03/2013; 45(1):31-9. -
Article: Long-term clinical experience of high-dose ablative lung radiotherapy: High pre-treatment [18F]Fluorodeoxyglucose-positron emission tomography maximal standardized uptake value of the primary tumor adversely affects treatment outcome.
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ABSTRACT: PURPOSE: The aim of this study was to report the long-term clinical experience with lung stereotactic ablative radiotherapy (SABR). METHODS: Between April 2004 and December 2011, 58 of 92 consecutive lung SABR cases were treated with a curative purpose and were eligible for inclusion. Forty patients were treated for primary lung cancer, and eighteen were treated for locally confined recurrent tumors. The majority of the cases were medically inoperable (65.5%). A median five fractions with a total dose of 30-60Gy were prescribed to the planned target volume. We routinely performed an image-guided respiratory gating technique or four-dimensional computed tomography to minimize set-up errors and accurately determine target volumes. RESULTS: The median follow-up was 23.8 (range, 1.5-77.2) months. The median age of the entire cohort was 73 (range, 48-90) years. The median gross tumor volume and maximal tumor diameter were 20 (range, 0.5-189.7) ml and 2.2 (range, 0.7-5.9) cm, respectively. The two-year local control (LC) rate was 92.1%, and the major pattern of failure was distant metastasis (25.9%). A high pre-treatment maximal standardized uptake value (mSUV) of the primary tumor significantly and adversely affected LC, local relapse-free survival, distant metastasis-free survival, cause-specific survival and overall survival. The toxicity rates (≥grade 2) were 34.5% and 35% for the central and peripheral tumors, respectively, and one grade 5 toxic event (death due to massive hemoptysis) occurred in a centrally located tumor at 16.7 months post-SABR. CONCLUSIONS: Lung SABR remains an effective and safe local treatment modality. Pre-treatment mSUV may be a helpful parameter to select patients requiring higher radiation doses and adjuvant systemic therapy for lung SABR.Lung cancer (Amsterdam, Netherlands) 02/2013; · 3.14 Impact Factor -
Article: Difference in expression of EGFR, pAkt, and PTEN between oropharyngeal and oral cavity squamous cell carcinoma.
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ABSTRACT: The aims of this study were to evaluate the expression of EGFR, PI3K, Akt, mTOR, and PTEN in the oral cavity and oropharyngeal cancers, and to investigate their clinical significance as prognostic markers. One hundred twenty-one patients who underwent curative surgery for oral cavity or oropharyngeal squamous cell carcinoma in Seoul St. Mary's Hospital between January 1995 and September 2009 were evaluated. The level of protein expression of EGFR, PIK3CA, pAkt, mTOR, and PTEN was assessed by immunohistochemistry. In situ hybridization was used to detect the existence of human papillomavirus (HPV). Nineteen of 61 patients with oropharyngeal cancer showed HPV-positive tumors, and two of 60 patients with oral cavity cancer showed HPV-positive tumors. EGFR and pAkt expression was significantly higher in oral cavity cancers than in oropharyngeal cancers. Loss of PTEN occurred significantly more frequently in oral cavity cancers than in oropharyngeal cancers. The expression levels of PIK3CA, mTOR, and p53 did not differ significantly between the two cancers. Overexpression of EGFR and pAkt and loss of PTEN were observed more frequently in HPV-negative tumors. Multivariate Cox regression analysis showed that pAkt expression had a significantly unfavorable impact on relapse-free survival in oropharyngeal cancer. We conclude that the expression levels of EGFR, pAkt, and PTEN differ between oropharyngeal and oral cavity cancer and it may be attributed to HPV-related molecular pathogenesis. The expression of pAkt might be an unfavorable prognostic marker for relapse-free survival in oropharyngeal cancer.Oral Oncology 06/2012; 48(10):985-90. · 2.86 Impact Factor -
Article: Randomized phase II trial of first-line treatment with pemetrexed-cisplatin, followed sequentially by gefitinib or pemetrexed, in East Asian, never-smoker patients with advanced non-small cell lung cancer.
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ABSTRACT: Treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors or chemotherapy have shown improved survival outcomes in East Asian, never-smoker patients with non-small cell lung cancer (NSCLC). However, treatment sequence has not been optimized in patients with unknown EGFR mutation status. This trial compared first-line chemotherapy with pemetrexed (P)-cisplatin (C), followed by either gefitinib (G) or P maintenance. East Asian, never-smoker, chemo-naïve patients with stage IIIB/IV NSCLC, performance status ≤1 and unknown EGFR mutation status were randomized 1:1 to receive 4 cycles of pemetrexed [500 mg/m(2)]+cisplatin [75 mg/m(2)] q3 weeks, followed by maintenance with either gefitinib [250 mg/d] (PC/G) or pemetrexed [500 mg/m(2)] q3 weeks and ≤2 optional cycles of cisplatin (PC/P). The primary endpoint, progression-free survival (PFS), was calculated from randomization date. Between Feb and Nov 2007, 70 patients from China, Korea, and Taiwan were randomized and treated, among whom 59 patients (84.3%) had non-squamous NSCLC. Forty-nine patients (70.0%) completed the full sequential treatment (n=25 G; n=24 P). Median PFS was numerically longer for patients on PC/G (9.95 months) than those on PC/P (6.83 months; hazard ratio [HR]=0.53, 95% confidence interval [CI]=0.27, 1.04). In contrast, median overall survival was numerically higher for patients on PC/P (HR=2.15, 95% CI=0.83, 5.60), though there was a high censoring rate. Response rate was similar in both arms. Treatment arms were similar for grade 3/4/5 toxicities. East Asian never-smoker patients with advanced NSCLC and unknown EGFR mutation status had improved PFS following treatment with first-line PC and sequential G. Irrespective of subsequent maintenance treatment, induction PC was safe and efficacious, leading to prolonged OS in the Asian patient population.Lung cancer (Amsterdam, Netherlands) 04/2012; 77(2):346-52. · 3.14 Impact Factor
