Efficacy and Safety of FOLFIRI Regimen in Elderly Versus Nonelderly Patients with Metastatic Colorectal or Gastric Cancer.

BACKGROUND: Irinotecan-based chemotherapy is a standard backbone of therapy in patients with metastatic colorectal cancer (CRC) or gastric cancer (GC). However, there is still a paucity of information concerning the efficacy and safety of irinotecan-based regimens in elderly patients. PATIENTS AND METHODS: Using the patient cohort (n = 1,545) from the UGT1A1 genotype study, we compared the efficacy and safety between elderly and nonelderly patients with metastatic CRC (n = 934) or GC (n = 611) who received first- or second-line FOLFIRI (irinotecan, leucovorin, and 5-fluorouracil) chemotherapy. RESULTS: Despite lower relative dose intensity in elderly patients, progression-free survival and overall survival were similar between elderly (age ≥70 years) and nonelderly (<70 years) patients in the CRC cohort (hazard ratio [HR], 1.117; 95% confidence interval [CI], 0.927-1.345; p = .244, and HR, 0.989; 95% CI, 0.774-1.264; p = .931, respectively) and the GC cohort (HR, 1.093; 95% CI, 0.854-1.400; p = .479, and HR, 1.188; 95% CI, 0.891-1.585; p = .241, respectively). In both cohorts, febrile neutropenia (22.1% vs. 14.6% in CRC cohort and 35.2% vs. 22.5% in GC cohort) and asthenia (grade 3: 8.4% vs. 1.7% in CRC cohort and 5.5% vs. 2.9% in GC cohort) were more frequent in elderly patients. In the CRC cohort, mucositis and anorexia were more frequent in elderly patients. In the GC cohort, nausea and vomiting were less frequent in elderly patients. CONCLUSION: The efficacy of the FOLFIRI regimen was similar between elderly and nonelderly patients in both the CRC and the GC cohorts. However, special attention should be paid to elderly patients because of increased risk for febrile neutropenia and asthenia. The Oncologist 2017;22:293-303 IMPLICATIONS FOR PRACTICE: The efficacy of FOLFIRI (irinotecan, leucovorin, and 5-fluorouracil) chemotherapy in elderly patients with metastatic colorectal cancer or gastric cancer was similar to that in nonelderly patients. However, special attention should be paid to elderly patients because of the increased risk for febrile neutropenia and asthenia. These data suggest that the FOLFIRI regimen could be considered as a standard backbone of therapy in elderly patients with metastatic colorectal cancer or gastric cancer and that the clinical decision between doublet and singlet chemotherapy may not be based solely on age. However, the data require further assessment of frailty and performance status.

Low-dose combinations of LBH589 and TRAIL can overcome TRAIL-resistance in colon cancer cell lines.

BACKGROUND: Despite the considerable advances in the treatment of colorectal cancer, substantial changes in treatment strategies are required to overcome the problems of drug resistance and toxicity. MATERIALS AND METHODS: Combinations of Pan-deacetylase inhibitor LBH589 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were studied in three colon cancer cell lines, HCT116, colo205, and HT29 (HCT116 and colo205 are TRAIL sensitive, whereas HT29 is TRAIL resistant). RESULTS: It was found that TRAIL-induced cytotoxicity was enhanced by LBH589 cotreatment in the TRAIL-sensitive cell lines, and in the TRAIL-resistant HT29 cell line. The cytotoxicity of low-dose TRAIL plus LBH589 was found to be comparable to that of high-dose TRAIL plus LBH589. Additionally, TRAIL and LBH589 were significantly less toxic to normal UCB mononuclear cells than to the three colon cancer cell lines examined. CONCLUSION: LBH589 enhances TRAIL-induced apoptosis in human colon cancer cell lines, especially those resistant to TRAIL-induced apoptosis.

Solitary extramedullary plasmacytoma of the liver without systemic monoclonal gammopathy.

Extramedullary plasmacytoma of the liver is a very rare tumor. Although a few cases of extramedullary plasmacytoma of the liver have been reported, we could not find any report on truly localized extramedullary plasmacytoma of the liver in the literature. The patient was a 63-yr-old man who exhibited a solitary liver mass on dynamic computed tomography and magnetic resonance imaging. Histologically, the tumor was composed of mature plasma cells with mild atypia. Immunohistochemistry demonstrated monoclonal IgG and Kappa light chain expression. Bone marrow examination revealed no abnormalities. There was no evidence of a monoclonal protein in the serum and urine, lytic bone lesions, anemia, renal insufficiency, and hypercalcemia. The patient was treated with 5,000 cGy of radiotherapy, and the tumor disappeared 6 months after treatment.

Co-transplantation of human mesenchymal stem cells promotes human CD34+ cells engraftment in a dose-dependent fashion in NOD/SCID mice.

Mesenchymal stem cells (MSCs) have recently been identified and characterized in humans. Moreover, MSC secrete cytokines that can support hematopoietic progenitor growth. In the present study, we evaluated whether the efficacy of hematopoietic stem cell transplantation is improved by their co-transplantation with MSC, and whether this is positively correlated with the dose of infused MSCs. Accordingly, irradiated NOD/SCID mice were transplanted with 1 x 10(5) human CD34+ cells in the presence or absence of culture expanded MSCs (1 x 10(6) or 5 x 10(6)). We evaluated human hematopoietic cell engraftment by flow cytometry and assessed MSC tissue distributions by fluorescence in situ hybridization. We found that CD45+ and CD34+ cell levels were significantly elevated in a dose-dependent manner in co-transplanted mice 4 weeks after transplantation. The engraftments of CD33+ and CD19+ cells also increased dose-dependently. However, the engraftment of CD3+ cells did not increase after co-transplantation with MSCs. Human Y chromosome+ cells were observed in multiple tissues and were more frequently observed in mice co-transplanted with 5 x 10(6) rather than 1 x 10(6) MSCs. These results suggest that MSCs are capable of enhancing hematopoietic cell engraftment and distribution in multiple organs in a dose-dependent fashion.

Successful eradication of relapsed primary effusion lymphoma with high-dose chemotherapy and autologous stem cell transplantation in a patient seronegative for human immunodeficiency virus.

Primary effusion lymphoma (PEL) is a recently recognized disease that occurs most often in immunosuppressed patients, either with human immunodeficiency virus (HIV) or in the posttransplantation setting, and it occasionally occurs in nonimmunosuppressed patients. Patients present with lymphomatous effusions in serous cavities--pleura, pericardium, or peritoneum--without any identifiable tumor mass. PEL rarely responds to systemic chemotherapy, and the prognosis is poor, with a median survival time of less than 6 months for most cohorts. A standard treatment for PEL has not yet been identified. We describe a patient with HIV-seronegative PEL who relapsed after combination chemotherapy and then underwent successful treatment with high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). The treatment was well tolerated, and the patient has been in remission for 12 months after HDC and ASCT.

A phase II study of irinotecan, 5-fluorouracil and leucovorin for treatment in patients with previously untreated advanced colorectal cancer.

PURPOSE: We prospectively conducted a non-randomized phase II trial to evaluate the efficacy and safety of combination irinotecan, leucovorin (LV) and 5-fluorouracil (FU) as a first-line regimen for treating patients with previously untreated advanced colorectal cancer (CRC). MATERIALS AND METHODS: Twenty-six previously untreated patients with advanced, recurrent or metastatic CRC were enrolled in this study. The patients received either irinotecan 180 mg/m(2) on day 1 with LV bolus of 200 mg/m(2) and FU bolus of 400 mg/m(2), and this was followed by FU continuous infusion of 600 mg/m(2) on day 1 and day 2 (the FOLFIRI regimen), or they were treated with LV bolus of 400 mg/m(2) and FU bolus of 400 mg/m(2) followed by FU continuous infusion of 2,400 mg/m(2) for 46 hours (the simplified FOLFIRI regimen), and these treatments were repeated every 2 weeks until disease progression. RESULTS: The objective response rate was 23.1% (6/26) respectively, for both treatments. The median time to progression was 5.3 months (range: 0.4 approximately 19.9), and the overall survival was 11.2 months (range: 0.5 approximately 52.3). The prognostic factor for longer survival was the Eastern Cooperative Oncology Group (ECOG) performance status (PS). The non-hematological toxicities were similar for both treatment groups, with more frequent grade >or=3 neutropenia being noted for the simplified FOLFIRI regimen. CONCLUSION: The biweekly irinotecan based regimen was demonstrated to have a moderate antitumor activity with acceptable toxicity profiles, and the ECOG PS was the independent prognostic factor.

Combination of gemcitabine and cisplatin as first-line therapy in advanced non-small-cell lung cancer.

PURPOSE: The prognosis of patients with advanced non-small-cell lung cancer (NSCLC) is extremely poor. Many prospective randomized trials on patients with advanced NSCLC suggested systemic chemotherapy improves both the survival and quality of life. A phase II trial was conducted to evaluate the efficacy and safety profile of the combination chemotherapy of gemcitabine and cisplatin in advanced NSCLC. MATERIALS AND METHODS: Forty-four patients with locally advanced or metastatic NSCLC were enrolled. The patients received a cisplatin, 75 mg/m(2), infusion over 30 minutes on days 1, followed by a gemcitabine, 1,250 mg/m(2), infusion over 30 minutes on days 1 and 8 every 3 weeks. RESULTS: The median age of the patients was 64 years (range: 27 approximately 75). Forty-one patients were assessable for response and toxicity analyses. The overall response rate was 53.6%, but with no complete remissions. The median time to progression was 5.6 months (range: 1 approximately 15.4). The median survival was 14.2 months (95% confidence interval (CI), 13.8 approximately 22.5). A total of 179 cycles were administered, with a median of 4 cycles of chemotherapy, ranging from 2 to 9 cycles. The most common hematological toxicities were NCI grades 3/4 neutropenia (24%) and thrombocytopenia (7.8%). The most common non-hematological toxicity was fatigue (42.4%). There were no life-threatening toxicity or treatment related mortalities. The median duration of follow up was 9.4 months, ranging from 1.6 to 30.3 months. CONCLUSION: In this trial, the combination of gemcitabine and cisplatin showed significant activity, with acceptable and manageable toxicities as a first-line regimen for patients with advanced NSCLC.

Metastasis to the Thigh Skeletal Muscle from an Adenocarcinoma of the Duodenum.

Skeletal muscle is one of the most unusual metastatic sites for any malignancy. Duodenal cancer is extremely rare, and no cases of skeletal muscle metastasis from duodenal cancer have been reported. We report here in a case of metastasis to the skeletal muscle of the left thigh from duodenal cancer. Our patient was a 47-year-old man, exhibiting a painful mass in the posterior aspect of his left thigh over a 4 month period. An imaging study, and a biopsy, revealed a duodenal adenocarcinoma metastasize to the skeletal muscle. The patient refused chemotherapy and has followed up for 4 months.

High Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation for Persistent/Relapsed Ovarian Cancer.

PURPOSE: High dose chemotherapy (HDC) is increasingly being used for ovarian cancer. Although early studies of autotransplantation for advanced ovarian cancer have been encouraging, most reported series were small, and no randomized trials have been reported. HDC and autologous hematopoietic stem cell transplantation were rarely performed in patients with ovarian cancer in Korea, and no results have been reported with the exception of one case report. MATERIALS AND METHODS: We retrospectively analyzed 10 patients with refractory or relapsed ovarian cancer having received HDC and autologous peripheral blood stem cell transplantation (APBSCT), between January 1996 and September 1998, at the Soon Chun Hyang and Ajou University Hospitals. RESULTS: Ten patients were treated with HDC and APBSCT. Six patients achieved complete response (CR) and 1 a partial response (PR), with a response rate of 70%. Three patients did not respond following mobilization chemotherapy, and failed to respond after HDC. The median duration of progression free survival (PFS) and overall survival (OS) were 6 (4~46) and 13 (3~50+) months, respectively. The median duration of OS of the responders following mobilization chemotherapy was 23 (8~50+) compared with 12 (3~18) months of the non- responders. With regard to the treatment related toxicity, 8 patients had neutropenic fevers, and bacteremia was documented in 4. The non-hematological toxicities were never life threatening, and there were no treatment related deaths. CONCLUSION: HDC, followed by APBSCT, is well-tolerated patients with refractory or relapsed ovarian cancer, and following mobilization chemotherapy the responders survived longer than the non-responders.