Namsu Lee

Intrathecal Trastuzumab Treatment in Patients with Breast Cancer and Leptomeningeal Carcinomatosis

Leptomeningeal carcinomatosis is a fatal manifestation of metastatic breast cancer. Investigation of intrathecal (IT) trastuzumab for leptomeningeal carcinomatosis is currently underway; however, there has been no consensus. We report on two cases of human epidermal growth factor receptor 2 positive (HER2+) breast cancer following IT trastuzumab for leptomeningeal carcinomatosis. The first patient was treated with weekly IT 15 mg methotrexate plus IT 50 mg trastuzumab for 7 months, followed by IT trastuzumab (50 mg > 25 mg) for 18 months. The other patient received IT trastuzumab with systemic chemotherapy (trastuzumab and/or paclitaxel) for 13 months. Good control of leptomeningeal disease was achieved with IT trastuzumab in both patients, with survival durations of 20 and 29 months, respectively. We suggest that IT trastuzumab is a promising treatment for patients with HER2+ breast cancer and leptomeningeal carcinomatosis.

Attenuated FOLFIRINOX in the salvage treatment of gemcitabine-refractory advanced pancreatic cancer: a phase II study

BackgroundCombination therapy with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) chemotherapy drastically improves survival of advanced pancreatic cancer patients. However, the efficacy of FOLFIRINOX as a second-line treatment after gemcitabine failure has not been tested prospectively. We investigated the feasibility and safety of attenuated FOLFIRINOX in patients with gemcitabine-refractory advanced pancreatic cancer.MethodsA multicenter phase II prospective open-label, single-arm study was conducted at 14 hospitals. Patients with histologically proven invasive ductal pancreatic adenocarcinoma, a measurable or evaluable lesion, Eastern Cooperative Oncology Group performance status 0 or 1, adequate organ function, and aged 19xa0years or older were eligible. Attenuated FOLFIRINOX consisted of oxaliplatin 65xa0mg/m2, irinotecan 135xa0mg/m2, and leucovorin 400xa0mg/m2 injected intravenously on day 1 and 5-fluorouracil 2000xa0mg/m2 continuously infused intravenously over 46xa0h on days 1–2, repeated every 2xa0weeks. The primary endpoint was progression-free survival from the initiation of FOLFIRINOX. Secondary endpoints were the objective response rate, disease control rate, overall survival, safety, and tolerability. We estimated overall survival and progression-free survival using the Kaplan–Meier methods.ResultsWe enrolled 39 patients from 14 institutions. The objective response rate was 10.3%, while the disease control rate was 64.1%. The 6-month and 1-year overall survival rates were 59.0% and 15.4%, respectively. Median progression-free survival and overall survival were 3.8xa0months (95% confidence interval [CI] 1.5–6.0xa0months) and 8.5xa0months (95% CI 5.6–11.4xa0months), respectively. Grade 3 or 4 adverse events were neutropenia (41.0%), nausea (10.3%), anorexia (10.3%), anemia (7.7%), mucositis (7.7%), pneumonia/pleural effusion (5.1%), and fatigue (5.1%). One treatment-related death attributable to septic shock occurred.ConclusionAttenuated FOLFIRINOX may be promising as a second-line therapy for gemcitabine-refractory pancreatic cancer.

Abstract 3844: Venous thromboembolism in patients with pancreatic cancer

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CAnnBackground:nnVenous thromboembolism (VTE) is a critical complication of malignant disease. Pancreatic cancer is one of the cancers most commonly associated VTE. In general, the VTE incidence rate of Asians is lower than that of Caucasians. In 2007, a Korean study reported that only four cases of VTE (5.3%) occurred in Seventy five patients with advanced pancreatic adenocarcinoma. We evaluated VTE incidence in pancreatic cancer and characteristics of pancreatic cancer patients with VTE.nnMethod:nnWe retrospectively reviewed the medical records of patients with histopathologically proven pancreatic cancer from January 2006 to December 2012 at Soonchunhyang university hospital. We detected VTE through CT (chest CT, pulmonary embolism CT) and low extremity ultrasoundgraphy.nnResultsnnFive hundred and fourteen patients with pancreatic adenocarcinoma were enrolled. (M: F, 300:214, localized: locally advanced: metastatic=31:230:253, mean age: 66.7 years). Ninety six of 514 patients (18.6%, symptomatic: aymptomatic=38:58, PE: DVT: PE+DVT: visceral thrombosis=20:19:19:38) were diagnosed as VTE. At the time of DVT diagnosis, cancer status of 50 patients cancer was progression, and that of 15 was stable. Thirty one patients were diagnosed with the pancreatic cancer and VTE, at the same time. They all had metastatic lesions. Fifty VTE patients were treated with antithrombotic therapy. Ninety three of 96 patients died, and three of them have probability that cause of death was VTE. The others died of pancreatic cancer progression. From pancreatic cancer diagnosis to VTE diagnosis, the period is 1.7month. (95%CI 1.1-2.3 month). Median overall survival (OS) was not significantly different between pancreatic cancer with VTE or without VTE. OS was significantly longer VTE patients after pancreatic cancer diagnosis than VTE patients with pancreatic cancer at the same time (10.73m vs. 1.7, p=0.00).nnConclusionnnThe incidence of VTE (18.6%) in Soonchunhyang university hospital with pancreatic cancer was not lower than that in western groups.nnCitation Format: Seug Yun Yoon, Namsu Lee, Sook-Ja Kim, Hee-Jeong Cheong, Kyoung Ha Kim, Jong-Ho Won, Hee Sook Park. Venous thromboembolism in patients with pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3844. doi:10.1158/1538-7445.AM2014-3844

Abstract 3843: Pulmonary toxicities of molecular targeted antineoplastic agents

Background A better understanding of cancer cell biology has suggested many new targets for cancer drug discovery and development. And these drugs are widely used in treating cancer and usually have good toxicity profiles. But some patients are exquisitely sensitive to these drugs and can develop particular and severe toxicities. Among the toxicities, pulmonary toxicities are infrequent with most commonly used targeted therapies. The aim of this study was to review the pulmonary toxicities caused by molecular targeted agents and analyze the various radiologic findings and clinical outcomes in these patients group. Methods We retrospectively reviewed the medical records and chest image findings of 549 patients who were treated by molecular targeted anti-neoplastic agents at Soonchunhyang University Hospital between May 2003 and September 2012. Patients who had chest image findings that suspected infection, pulmonary hemorrhage caused by other cause and primary disease progression were excluded. Results Of these 549 patients, 364 patients performed chest CT or HRCT during targeted agent therapy. Thirty-four patients (6.2%) with drug induced pulmonary toxicities confirmed by radiologist and oncologist were identified. The most common targeted agent that induced pulmonary toxicities was gefitinib (9/34 patients), followed by rituximab, imatinib, erlotinib, cetuximab, trastuzumab, bevacizumab, bortezomib, and dasatinib. Pneumonitis (44.1%) and pleural effusion (32.4%) were common radiological findings. Dyspnea was the main presenting initial symptom and proportion in symptomatic patients (18/34 patients, 52.9%) was mostly 83.3% (15/18 patients). Sixteen patients stopped being treated with targeted agents, 11 patients were simultaneously treated with glucocorticoids. Sixteen patients did not receive any other treatment and were observed with regular follow ups. Of 34 patients, 20 patients (58.8%) resolved pulmonary toxicity from chest CT imaging. There were four patients (11.7%) who died from drug related pulmonary toxicity. Conclusion Pulmonary toxicities caused by targeted agents are rare but important to recognize. Dyspnea appears to be the main presenting symptom. In conclusion, we should be aware of pulmonary toxicities and symptoms presenting dyspnea during targeted agent therapy. If we suspect drug induced pulmonary toxicities, we should perform immediate imaging studies and keep a possibility of variable radiological patterns in mind. The cessation of the implicated causative targeted agents and treatment with systemic glucocorticoids resulted in an improvement both in symptoms and image findings, but fatal pulmonary toxicities occurred in some patients. Citation Format: Seug Yun Yoon, Namsu Lee, Sook-Ja Kim, Hee-Jeong Cheong, Kyoung Ha Kim, Jong-Ho Won. Pulmonary toxicities of molecular targeted antineoplastic agents. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3843. doi:10.1158/1538-7445.AM2014-3843

Pathophysiological role of hormones and cytokines in cancer cachexia.

leptin was significantly lower in cachectic patients than in the comparison group (15.3 ± 19.5 vs 80.9 ± 99.0 pg/mL, P = 0.007). During the follow-up, the patients who showed a > 5% weight gain had higher ghrelin levels after 6 months. Patients exhibiting elevated IL-6 levels typically showed a weight loss > 5% after 6 months. A blunted adiponectin or ghrelin response to weight loss may contribute to cancer cachexia and IL-6 may be responsible for inducing and maintaining cancer cachexia.