Woon Ki Lee

A phase II study of epirubicin, cisplatin and capecitabine combination chemotherapy in patients with metastatic or advanced gastric cancer

Objectives: The purpose of this study was to evaluate the antitumor activity and safety of an epirubicin, cisplatin, and capecitabine (ECX) combination in patients with metastatic or advanced gastric cancer. Patients and Methods: Patients with metastatic or advanced measurable gastric adenocarcinoma received ECX combination chemotherapy. Epirubicin 50 mg/m2 and cisplatin 60 mg/m2 were administered on day 1 by intravenous injection. Capecitabine 1,000 mg/m2 twice daily was administered orally on day 1–14. The cycle was repeated every 3 weeks. Results: Fifty-four patients were enrolled in this study. Fifty patients were assessable for responses and 53 for toxicity. A total of 250 cycles were administered. The overall best response rate by intent-to-treat analysis was 59% including 52% partial responses and 7% complete responses. Median response duration and time to progression was 5.8 and 6 months, respectively. Median survival for all patients was 9.6 months (95% CI, 8.7–10.5 months). The most common grade 3/4 hematological adverse event was neutropenia in 31% (76 cycles) including febrile neutropenia in 4.8% (11 cycles). Non-hematological toxicity was generally mild and reversible. Grade 3/4 nausea, vomiting and stomatitis occurred in 8, 9, and 8% of the patients, respectively. Hand-foot skin reactions developed in 51% of patients, but most were self-limited. Grade 3 occurred in only 4%. One patient died of neutropenic sepsis. Conclusions: ECX combination regimen showed high anti-tumor activity with a tolerable toxicity pattern as a front-line chemotherapy for patients with metastatic or advanced gastric cancer.

Quality of life in patients with advanced gastric cancer treated with second-line chemotherapy

Objective: Despite many trials of systemic chemotherapy in advanced gastric cancer, treatment after failure with first-line chemotherapy remains controversial. We prospectively assessed quality of life (QL) in gastric cancer patients treated with second-line chemotherapy. Methods: Forty-three patients who received second-line chemotherapy for advanced gastric cancer completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and hospital anxiety and depression scale (HADS) at baseline and at regular intervals during and after chemotherapy. Results: Compliance with QL questionnaire completion decreased to 72% after third cycle of treatment. In general, clinically meaningful improvements compared with baseline (change QLQ-C30 scores ≥10) were seen in a number of domains and items, including global health/QL, emotional function, cognitive function and all of the symptom scales and single items but appetite. There was no difference in QL between responders and non-responders (P=0.473). At baseline, 27 (63%) patients were suspected to have anxiety or depressive disorder (HADS score ≥11), and this incidence decreased after chemotherapy (14.7 vs 9.5; P<0.001). Conclusion: Improvements from baseline in QL measures and HADS scores were demonstrated in patients with advanced gastric cancer, treated with second-line chemotherapy.

Laparoscopy Assisted versus Open Distal Gastrectomy with D2 Lymph Node Dissection for Advanced Gastric Cancer: Design and Rationale of a Phase II Randomized Controlled Multicenter Trial (COACT 1001)

Purpose Laparoscopy-assisted distal gastrectomy for early gastric cancer has gained acceptance and popularity worldwide. However, laparoscopy-assisted distal gastrectomy for advanced gastric cancer is still controversial. Therefore, we propose this prospective randomized controlled multi-center trial in order to evaluate the safety and feasibility of laparoscopy assisted D2-gastrectomy for advanced stage gastric cancer. Materials and Methods Patients undergoing distal gastrectomy for advanced gastric cancer staged cT2/3/4 cN0/1/2/3a cM0 by endoscopy and computed tomography are eligible for enrollment after giving their informed consent. Patients will be randomized either to laparoscopy-assisted distal gastrectomy or open distal gastrectomy. Sample size calculation revealed that 102 patients are to be included per treatment arm. The primary endpoint is the non-compliance rate of D2 dissection; relevant secondary endpoints are three-year disease free survival, surgical and postoperative complications, hospital stay and unanimity rate of D2 dissection evaluated by reviewing the intraoperative video documentation. Discussion Oncologic safety is the major concern regarding laparoscopy-assisted distal gastrectomy for advanced gastric cancer. Therefore, the non-compliance rate of clearing the N2 area was chosen as the most important parameter for the technical feasibility of the laparoscopic procedure. Furthermore, surgical quality will be carefully reviewed, that is, three independent experts will review the video records and score with a check list. For a long-term result, disease free survival is considered a secondary endpoint for this trial. This study will offer promising evidence of the feasibility and safety of Laparoscopy-assisted distal gastrectomy for advanced gastric cancer.Trial Registration: NCT01088204 (international), NCCCTS-09-448 (Korea).

Three-year experience of pouch dilatation and slippage management after laparoscopic adjustable gastric banding.

Purpose Pouch dilatation and band slippage are the most common long-term complications after laparoscopic adjustable gastric banding (LAGB). The aim of the study is to present our experience of diagnosis and management of these complications. Materials and Methods The pars flaccida technique with anterior fixation of the fundus was routinely used. All band adjustments were performed under fluoroscopy. We analyzed the incidence, clinico-radiologic features, management, and revisional surgeries for treatment of these complications. We further presented the outcome of gastric plication techniques as a measure for prevention of these complications. Results From March 2009 to March 2012, we performed LAGB on 126 morbidly obese patients. Among them, 14 patients (11.1%) were diagnosed as having these complications. Four patients (3.2%) had concentric pouch dilatations, which were corrected by band adjustment. Ten (7.9%) had eccentric pouch with band slippage. Among the ten patients, there were three cases of posterior slippage, which were corrected by reoperation, and seven cases of eccentric pouch dilatation with anterior slippage. Three were early anterior slippage, which was managed conservatively. Two were acute anterior slippage, one of whom underwent a revision. There were two cases of chronic anterior slippage, one of whom underwent a revision. The 27 patients who underwent gastric plication did not present with eccentric pouch with band slippage during the follow-up period. Conclusion The incidence of pouch dilatation with/without band slippage was 11.1%. Management should be individualized according to clinico-radiologic patterns. Gastric plication below the band might prevent these complications.

Synchronous Peripancreatic Lymph Node Gastrinoma and Gastric Neuroendocrine Tumor Type 2.

A 34-year-old man was referred to our hospital with gastric polypoid lesions and biopsy-confirmed neuroendocrine tumor (NET). Computed tomography (CT) revealed a 3×3.5×8-cm retroperitoneal mass behind the pancreas, with multiple hepatic metastases. His serum gastrin level was elevated to 1,396 pg/mL. We performed a wedge resection of the stomach, a right hemi-hepatectomy, and a retroperitoneal mass excision. After careful review of the clinical, radiological, histopathological, and immunohistochemical findings, peripancreatic gastrinoma, and synchronous gastric NET were ultimately diagnosed. We reviewed a CT scan that had been performed 6 years previously after surgery for a duodenal perforation. There was no evidence of gastric or hepatic lesions, but the retroperitoneal mass was present at the same site. Had gastrinoma been detected earlier, our patient could have been cured using less invasive treatment. This case demonstrates how important it is to consider Zollinger-Ellison syndrome in patients with a recurrent or aggressive ulcer.

A Pilot Study of Cisplatin, Irinotecan, Leucovorin and 5-fluorouracil (PILF) Combination Chemotherapy for Advanced Gastric Cancer

PURPOSE Irinotecan, in combination with leucovorin/5-fluorouracil (FU) or with cisplatin, is known to be active for treating advanced gastric cancer (AGC). This pilot study evaluated a novel three-drug combination of irinotecan, leucovorin/FU and cisplatin as a first-line treatment of AGC. The primary endpoint was to assess the feasibility in anticipation of conducting a larger phase II study. MATERIALS AND METHODS Chemotherapy-naive AGC patients received irinotecan 150 mg/m(2) on day 1, and leucovorin 200 mg/m(2) and a 22-h infusion of FU 1000 mg/m(2) on days 1 and 2. Cisplatin 30 mg/m(2) was administered on day 2. Treatment was repeated every 2 weeks until disease progression or unacceptable toxicity. RESULTS Of the 17 eligible patients, two patients had an ECOG performance status of 2 and their median age was 48 years (range: 31 to 69). A total of 117 chemotherapy cycles were delivered (median: 6, range: 1 to 12). The causes of treatment discontinuation were disease progression in 9 patients (53%), refusal (35%) and toxicity (12%). Although grade 3 or 4 neutropenia (41% of patients) was the major toxicity that required dose adjustments, only one episode of febrile neutropenia occurred. Grade 3 or 4 nausea and vomiting, diarrhea and fatigue were observed in 35%, 35% and 29% of patients, respectively. None of the patients died of toxicity during treatment. Of the 16 patients who were evaluable for response, 7 (44%) experienced a partial response. CONCLUSION This novel multi-drug combination was tolerated well in patients with AGC. Based on the encouraging efficacy and tolerability, a randomized phase II study is ongoing in this disease setting.

Phase I dose-escalating study of docetaxel in combination with 5-day continuous infusion of 5-fluorouracil in patients with advanced gastric cancer

BackgroundPublished data suggests that docetaxel combined with 5-fluorouracil (5-FU) may have synergistic activity in treating advanced gastric cancer. We performed a phase I study of docetaxel and 5-FU to determine the maximum tolerated dose (MTD), the recommended dose for phase II studies, and the safety of this combination.MethodsEligible patients had recurrent and/or metastatic advanced gastric cancer with normal cardiac, renal and hepatic function. Traditional phase I methodology was employed in assessing dose-limiting toxicity (DLT) and MTD. On day 1 every 3 weeks, docetaxel 75 mg/m2 (fixed dose) was infused over 1-h, followed immediately by 5-FU as a 5-day continuous infusion.ResultsDose escalation schema was as follows: dose level (DL) 1 (5-FU 250 mg/m2/day), 2 (500), 3 (750), and 4 (1000). Three patients were enrolled on DL1, without DLT. On DL2, 1 DLT (grade 3 stomatitis) was developed in first 3 patients, and this cohort was expanded to 6 patients. Three patients had been enrolled on DL3. Because two out of 3 patients had DLTs, the MTD was reached at DL3.ConclusionThe recommended phase II dose of this combination is 75 mg/m2 docetaxel on day 1 immediately followed by a 5-day continuous infusion of 5-FU 500 mg/m2/day.

A pilot study of low-dose capecitabine plus trastuzumab as first-line treatment for patients older than 75 years with HER2-positive advanced gastric cancer.

165 Background: Elderly patients often present with concomitant co-morbidities and age-associated physiologic problems, such as impaired organ function and functional changes that make the selection of optimal treatment difficult. We report the treatment outcome in 13 elderly patients with HER2-positve advanced gastric cancer who treated with low-dose capecitabine plus trastuzumab. Methods: Patients older than 75 years with gastric cancer were eligible for inclusion if their tumors showed overexpression of HER2 protein by immunohistochemistry (IHC) (3+) or gene amplification by FISH and IHC 2+. Capecitabine 1000 mg/m2was given orally twice a day for 14 days followed by a 1-week rest. Trastuzumab was given by intravenous infusion as a dose of 8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks. Chemotherapy was given every 3 weeks for eight cycles. Results: Between December 2011 and July 2013, 13 consecutive patients (IHC 3+;7, IHC 2+ and FISH+;6) with a median age of 79 years (range, 75...