Hoon Gu Kim

A multicenter, phase II trial of everolimus in locally advanced or metastatic thyroid cancer of all histologic subtypes

BACKGROUND This phase II study investigated the efficacy and safety of everolimus, an inhibitor of mammalian target of rapamycin (mTOR), in locally advanced or metastatic thyroid cancer. PATIENTS AND METHODS Patients with thyroid cancer of any histology that was resistant or not appropriate for (131)I received everolimus 10 mg daily orally until unacceptable toxicity or disease progression. The primary end point was disease control rate [partial response (PR) + stable response ≥12 weeks]. Secondary end points included response rates, clinical benefit (PD + durable stable disease (SD)], progression-free survival (PFS), overall survival, duration of response, and safety. RESULTS Thirty-eight of 40 enrolled patients were evaluable for efficacy. The disease control rate was 81% and two (5%) patients achieved objective response; their duration of response was 21+ and 24+ weeks. Stable disease (SD) and progressive disease was reported in 76% and 17% of patients, respectively. Seventeen (45%) patients showed durable SD (≥24 weeks) and clinical benefit was reported in 19 (50%) patients. Median PFS was 47 weeks [95% confidence interval (CI) 14.9-78.5]. Calcitonin, CEA, and thyroglobulin concentrations were ≥50% lower than baseline in three (30%) and four (44%) patients with medullary thyroid cancer and five (33%) patients with PTC, respectively. The most common treatment-related adverse events were mucositis (84%), anorexia (44%), and aspartate transaminase/alanine transaminase elevation (26%). CONCLUSIONS Everolimus had a limited activity with low response rate in locally advanced or metastatic thyroid cancer. Reasonable clinical benefit rate and safety profile may warrant further investigation. CLINICALTRIALSGOV NUMBER NCT01164176.

Characterization of a profile of the anthocyanins isolated from Vitis coignetiae Pulliat and their anti-invasive activity on HT-29 human colon cancer cells.

We isolated anthocyanins from fruits of Vitis coignetiae Pulliat, characterized the anthocyanin profile, and investigated the anti-invasive effects of the anthocyanins on human colon cancer cells. The anthocyanins inhibited cell invasion in a dose-dependent manner, as measured by Matrigel invasion assays, by suppression of matrix metalloproteinase (MMP)-2 and MMP-9 expression. The anti-invasive activity of the anthocyanins was associated with modulation of constitutive nuclear factor kappaB (NF-kappaB) activation. The activation of NF-kappaB triggered by tumor necrosis factor-alpha was also inhibited by the anthocyanins through suppression IkappaBalpha phosphorylation. AIMs inhibited the expression of NF-kappaB-regulated proteins. In conclusion, this study suggested that the anthocyanins isolated from fruits of V. coignetiae Pulliat should have anti-invasive activities on human colon cancer cells and the activities should be related to the inhibition of NF-kappaB-regulated proteins such as MMP-2 and MMP-9 expression through the inhibition of NF-kappaB activation.

A prospective multicenter observational study of decitabine treatment in Korean patients with myelodysplastic syndrome

Background Decitabine was evaluated for its efficacy and safety in Korean patients with myelodysplastic syndrome with IPSS score of 0.5 or over. Design and Methods Decitabine 20 mg/m2/day was given intravenously over one hour for five consecutive days every four weeks. The primary end point was overall response rate. Results A total of 101 patients were analyzed. The International Prognostic Scoring System risk category was Intermediate-2/High in 47.5%. A median of 5 courses (range 1–18) were delivered. The overall response rate was 55.4% (13 complete responses, one partial response, 23 marrow complete responses, and 19 hematologic improvements). Forty-eight patients (47.5%) showed some hematologic improvement. With a median follow-up duration of 478 days (range 69–595), median overall survival was 17.7 months. Patients who showed hematologic improvement had significantly longer overall survival than those who did not (19.2 vs. 15.9 months, P=0.006 by landmark analysis at six months). The difference in overall survival was evident in the Intermediate-2/High risk group but not in the Intermediate-1 risk group. The progression-free survival and acute myeloid leukemia-free survival were 61.9% and 77.9% at one year, respectively. Among 489 assessable treatment courses, there were 97 fever episodes requiring intravenous antimicrobials. Conclusions Decitabine treatment was feasible and effective in Korean patients with myelodysplastic syndrome, and the overall survival was significantly longer in patients showing hematologic improvement.

Corticosteroid Rotation to Alleviate Dexamethasone-Induced Hiccup: A Case Series at a Single Institution

Dexamethasone, one of the key medications for the prevention of chemotherapy-induced nausea and vomiting (CINV), may cause hiccups as an adverse effect. In this case series, we present five patients who developed hiccups after receiving dexamethasone for CINV. We successfully switched dexamethasone to an equipotent dosage of either methylprednisolone or prednisolone, which resolved the hiccups while maintaining adequate control of CINV. This was achieved without changing the rest of the antiemetic regimen, chemotherapy doses, or the use of other medications such as baclofen, haloperidol, and metoclopramide for hiccups. Further studies on switching dexamethasone to alternative corticosteroids in patients developing hiccups after administration of dexamethasone are warranted.

Phase II Trial of S-1 in Combination with Oxaliplatin in Previously Untreated Patients with Recurrent or Inoperable Biliary Tract Cancer

Background: Biliary tract cancers are among the most aggressive tumors with a poor prognosis. We conducted a phase II study on combination chemotherapy consisting of S-1 and oxaliplatin in previously untreated patients . Methods: Patients were treated with S-1 40 mg/m2 twice daily, administered orally on days 1–28, and 85 mg/m2 of oxaliplatin, administered via an intravenous 90-min infusion on days 1, 15 and 29. Treatments were repeated every 6 weeks. Results: 15 patients were enrolled: 9 patients (60%) had intrahepatic and 3 (20%) had extrahepatic cholangiocarcinoma, 2 (13.3%) had cancer of the ampulla of Vater and 1 patient had gall bladder cancer. Partial response was observed in 1 of the 15 (6.7%) patients. Stable disease was observed in 4 patients (26.7%). The median time to progression was 1.4 months (95% confidence interval, CI, 0.9–1.9), and the median overall survival was 3.1 months (95% CI, 0.0–7.0). Grade 3 hematologic toxicities included neutropenia (1, 6.7%) and thrombocytopenia (1, 6.7%). As the response rate in stage I did not justify progression to stage II (≧2/15), this study had to be discontinued in accordance with the established protocols. Conclusion: The combination chemotherapy with S-1 and oxaliplatin utilized in this study resulted in no promising antitumor activity.

An open label, multicenter, phase II study of dovitinib in advanced thyroid cancer

BACKGROUND This phase 2 study investigated the efficacy and safety of dovitinib (TKI258), a receptor tyrosine kinase inhibitor with potent activity against fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR), in locally advanced or metastatic thyroid cancer patients. PATIENTS AND METHODS Patients with advanced thyroid cancer that was refractory or not appropriate for (131)I received dovitinib orally, 500mg once daily for five consecutive days, followed by a 2-day rest every week. The primary end-point was objective response rate. Secondary end-points were progression-free survival (PFS), overall survival (OS), duration of response, changes in tumour markers and safety. RESULTS Between January 2013 and October 2014, a total of 40 patients were enrolled. There were 23 (57.5%) papillary thyroid cancer, 12 (30%) medullary thyroid cancer and 5 (12.5%) follicular thyroid cancer patients. One patient had withdrawn consent before the administration of dovitinib. The overall response rate was 20.5% (8/39) and disease control rate was 69.1% (26/39). Median PFS was 5.4 months (95% confidence interval (CI), 2.0-8.8) and median OS was not reached with 8.4 months follow-up duration. Common treatment-related adverse events were diarrhoea (53.8%), anorexia (35.8%), vomiting (25.6%), fatigue (23%) and nausea (20.5%), most of which were grade 1 or 2. There were no grade 4 events or treatment-related deaths. Dose interruption occurred in 12 (30.7%) patients, and 19 (48.7%) patients experienced dose reduction due to adverse events. CONCLUSIONS Dovitinib has a modest activity with manageable toxicity in locally advanced or metastatic thyroid cancer.

Concurrent chemoradiotherapy for elderly patients with stage III non-small cell lung cancer

Purpose Combined chemoradiotherapy is standard management for locally advanced non-small cell lung cancer (LA-NSCLC), but standard treatment for elderly patients with LA-NSCLC has not been confirmed yet. We evaluated the feasibility and efficacy of concurrent chemoradiotherapy (CCRT) for elderly patients with LA-NSCLC. Materials and Methods Among patients older than 65 years with LA-NSCLC, 36 patients, who underwent CCRT were retrospectively analyzed. Chemotherapy was administered 3-5 times with 4 weeks interval during radiotherapy. Thoracic radiotherapy was delivered to the primary mass and regional lymph nodes. Total dose of 54-59.4 Gy (median, 59.4 Gy) in daily 1.8 Gy fractions and 5 fractions per week. Results Regarding the response to treatment, complete response, partial response, and no response were shown in 16.7%, 66.7%, and 13.9%, respectively. The 1- and 2-year overall survival (OS) rates were 58.2% and 31.2%, respectively, and the median survival was 15 months. The 1- and 2-year progression-free survivals (PFS) were 41.2% and 19.5%, respectively, and the median PFS was 10 months. Regarding to the toxicity developed after CCRT, pneumonitis and esophagitis with grade 3 or higher were observed in 13.9% (5 patients) and 11.1% (4 patients), respectively. Treatment-related death was not observed. Conclusion The treatment-related toxicity as esophagitis and pneumonitis were noticeably lower when was compared with the previously reported results, and the survival rate was higher than radiotherapy alone. The results indicate that CCRT is an effective in terms of survival and treatment related toxicity for elderly patients over 65 years old with LA-NSCLC.

Successful Treatment of Syncope with Chemotherapy Irresponsive to Cardiac Pacemaker in Head and Neck Cancer

Recurrent syncope as a complication of recurrent neck malignancy is an uncommon but well documented association. The syncope is presumed to occur when a tumor mass invades the baroreceptor within the carotid sinus or when it disrupts the afferent nerve fibers of the glossopharyngeal nerve. A 59-year-old man presented with recurrent syncope and headache. He had a wide local excision including tonsillectomy and modified left radical neck dissection for tonsilar cancer 4 years ago. A computed tomography scan revealed ill-defined lesions in left parapharyngeal, carotid space and right upper jugular region. After clinical evaluation, cardiac pacemaker was placed, but he still suffered from the syncope. Then, he received the chemotherapy with docetaxel and cisplatin. The last hypotension event occurred on day 10 of the chemotherapy. Six months after 3 cycles of chemotherapy, he remained in complete remission and resolution of syncope. We report a case in which syncope was associated with a recurrence of tonsilar cancer and successfully treated with chemotherapy.

Effect of early chemoradiotherapy in patients with limited stage small cell lung cancer

Purpose We evaluated the effect of early chemoradiotherapy on the treatment of patients with limited stage small cell lung cancer (LS-SCLC). Materials and Methods Between January 2006 and December 2011, thirty-one patients with histologically proven LS-SCLC who were treated with two cycles of chemotherapy followed by concurrent chemoradiotherapy and consolidation chemotherapy were retrospectively analyzed. The chemotherapy regimen was composed of etoposide and cisplatin. Thoracic radiotherapy consisted of 50 to 60 Gy (median, 54 Gy) given in 5 to 6.5 weeks. Results The follow-up period ranged from 5 to 53 months (median, 22 months). After chemoradiotherapy, 35.5% of the patients (11 patients) showed complete response, 61.3% (19 patients) showed partial response, 3.2% (one patient) showed progressive disease, resulting in an overall response rate of 96.8% (30 patients). The 1-, 2-, and 3-year overall survival (OS) rates were 66.5%, 41.0%, and 28.1%, respectively, with a median OS of 21.3 months. The 1-, 2-, and 3-year progression free survival (PFS) rates were 49.8%, 22.8%, and 13.7%, respectively, with median PFS of 12 months. The patterns of failure were: locoregional recurrences in 29.0% (nine patients), distant metastasis in 9.7% (three patients), and both locoregional and distant metastasis in 9.7% (three patients). Grade 3 or 4 toxicities of leukopenia, anemia, and thrombocytopenia were observed in 32.2%, 29.0%, and 25.8%, respectively. Grade 3 radiation esophagitis and radiation pneumonitis were shown in 12.9% and 6.4%, respectively. Conclusion We conclude that early chemoradiotherapy for LS-SCLC provides feasible and acceptable local control and safety.

Milling Characteristics of Milled Rice According to Milling Ratio of Friction and Abrasive Milling

This study was performed to investigate the optimum abrasive and friction milling ratio. This was accomplished by determining changes in the quality, such as whiteness, moisture content, broken kernel, unstripped embryo rate, and surface characteristics or milling difference, during an abrasive and friction based milling process. When only abrasive was milled, the increase of whiteness was fast in the first milling, whereas the increasing rate of whiteness was small in the latter milling. The decreasing rate of moisture content and broken kernel increased as the friction milling ratio was increased. Combining with the friction milling was considered a suitable method because the unstripped embryo rate was high only when abrasive milling was used. In the case of a high abrasive milling ratio, a significant milling difference was observed in the initial milling. This indicated that the milling difference was not completely eliminated despite using friction milling in the latter milling. Consequently, it was necessary to minimize the milling difference in the initial milling. When milling quality was synthetically considered, the abrasive milling ratio was varied from 20~50%. When the abrasive milling ratio was greater than 40%, the external quality of the rice milled deteriorated since holes and defects generated on the surface in the initial milling were not removed. Due to this deterioration in surface characteristics, an abrasive milling ratio of 30% was identified as a suitable level.