Sang-Cheol Lee

Bronchial hyperreactivity in patients with endobronchial tuberculosis

Some patients with endobronchial tuberculosis (EBTB) have wheeze on physical examination and normal chest PA, which mimic bronchial asthma. Non-specific bronchial challenge tests have been used to confirm the presence of bronchial hyperreactivity, which is a hallmark of bronchial asthma. To evaluate the effect of endobronchial tuberculous inflammation on bronchial responsiveness to histamine, the provocation concentrations of histamine required to reduce FEV1 by 20% of the pre-challenge baseline (PC20) were compared between patients with EBTB, patients with symptomatic bronchial asthma and normal, healthy controls. PC20 in EBTB patients (17.2 +/- 2.3 mg ml-1) and normal controls (19.5 +/- 1.4 mg ml-1) were significantly higher than in bronchial asthma patients (0.99 +/- 0.15 mg ml-1). PC20 in EBTB patients was not affected by disease location in the bronchial tree was not correlated with FVC or FEV1. In conclusion, one should consider the possibility of EBTB for differential diagnosis from bronchial asthma, if airway responsiveness appears normal in wheezy patients.

Retrospective analyses of cisplatin-based doublet combination chemotherapy in patients with advanced gastric cancer

BackgroundsCisplatin-based chemotherapy, in combination with fluoropyrimidines or taxanes, have demonstrated efficacy against advanced gastric cancer (AGC). This retrospective study was performed with the data obtained from our cancer chemotherapy registry and eight another cancer centers.MethodsIn 2008, a total of 283 AGC patients were treated with cisplatin-based doublet chemotherapy in the first-line setting: capecitabine plus cisplatin (XP, n = 77), S-1 plus cisplatin (SP, n = 97), taxanes (docetaxel, paclitaxel) plus cisplatin (TP, n = 72), and 5-fluorouracil plus platinum (FP, n = 37). The primary endpoint of this study was overall survival (OS) and the secondary endpoints were safety, response rate and progression-free survival (PFS).ResultsThe median age was 54 years with a range of 28-78 years and median delivered number of chemotherapy cycles were XP: 4, SP: 5, TP: 5 and FP: 5, respectively. Objective tumor responses (38%; 95% CI, 32-43%) were 40% for XP, 42% for SP, 36% for DP, and 24% for FP. The estimated median PFS was 4.5 months (95% CI, 3.6-5.4 months) and the median OS was 12.3 months (95% CI, 10.8-13.7 months). No statistically significant difference was found between each regimen used as first-line chemotherapy. At multivariate analysis, independent prognostic parameters for OS were prior gastrectomy, peritoneal dissemination, performance status and hemoglobin levelConclusionAll of the cisplatin-based doublet chemotherapy regimens appear to be active as first-line chemotherapy for AGC. With better patient selection according to clinical parameters and molecular markers, clinical outcomes of AGC patients in first-line setting can be improved.

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.

A Phase II Study of Weekly Docetaxel as Second-Line Chemotherapy in Patients With Metastatic Urothelial Carcinoma.

UNLABELLEDnThe present multicenter phase II study evaluated the efficacy and safety of weekly docetaxel as second-line chemotherapy for metastatic urothelial carcinoma. Weekly docetaxel was well tolerated but demonstrated modest activity, with a response rate of 6%, a median progression-free survival (PFS) of 1.4 months, and a median overall survival (OS) of 8.3 months. The dichotomy between PFS and OS was likely associated with subsequent platinum-based chemotherapy received by 58% of the patients.nnnBACKGROUNDnDocetaxel is commonly used for second-line therapy for metastatic urothelial carcinoma (UC). However, myelosuppression is a substantial concern when the traditional 3-week docetaxel cycle is used. The present multicenter phase II study evaluated the efficacy and safety of weekly docetaxel as second-line chemotherapy for metastatic UC.nnnPATIENTS AND METHODSnPatients with progression after previous platinum-based chemotherapy for advanced or metastatic disease were treated with docetaxel 30 mg/m(2) on days 1 and 8 every 21 days. The primary endpoint was the response rate.nnnRESULTSnThe study enrolled 31 patients. Their median age was 64 years (range, 40-79 years). An Eastern Cooperative Oncology Group performance status of 1, liver metastasis, and a hemoglobin level < 10 g/dL were observed in 100%, 32%, and 23% of patients, respectively. Previous platinum-based chemotherapy had been administered for metastatic disease in 29 patients (94%). Although fatigue (13%) and anorexia (6%) were the most frequently observed grade 3 to 4 toxicities, the safety profiles were generally mild and manageable. Two patients (6%) achieved an objective response, which was maintained for 3.0 to 7.8 months. Eight patients experienced disease stabilization (disease control rate, 32%). The median progression-free survival (PFS) and overall survival (OS) were 1.4 months (95% confidence interval [CI], 1.3-1.6) and 8.3 months (95% CI, 5.9-10.6), respectively. A relatively long OS was associated with further salvage platinum-based chemotherapy (n = 18, 58%) showing an encouraging activity (response rate, 44%; median PFS, 4.0 months).nnnCONCLUSIONnSecond-line chemotherapy with weekly docetaxel was well tolerated but demonstrated modest activity in patients with metastatic UC. A platinum-based combination as second-line treatment might be considered for selected patients.

A Case of Central Nervous System Myelomatosis with Complex Chromosome Aberrations

Involvement of the central nervous system is very uncommon in multiple myeloma, observed in approximately 1% of the multiple myeloma patients. We report a case of central nervous system myelomatosis with complex chromosome aberrations in a 62-yr-old female patient, who had previously been diagnosed as multiple myeloma. Fluorescent in situ hybridization revealed 13q deletion, p53 gene deletion and IGH/FGFR3 rearrangement and chromosomal study showed complex chromosome aberrations. After four cycles of chemotherapy, the patient was admitted to the hematology department with severe headache. Plasma cells were found in the cerebrospinal fluid (CSF), and CSF immunoelectrophoresis revealed abnormal precipitin arcs against anti-IgG and anti-lambda antisera. She was given systemic chemotherapy and eight courses of intrathecal chemotherapy, which cleared plasma cells in the CSF. Two months later, she was given autologous stem cell transplantation. Three months after stem cell transplantation, central nervous system myelomatosis progressed to plasma cell leukemia and two months later, the patient expired.

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.