PRODIGY: A Phase III Study of Neoadjuvant Docetaxel, Oxaliplatin, and S-1 Plus Surgery and Adjuvant S-1 Versus Surgery and Adjuvant S-1 for Resectable Advanced Gastric Cancer.

PURPOSE: Adjuvant chemotherapy after D2 gastrectomy is standard for resectable locally advanced gastric cancer (LAGC) in Asia. Based on positive findings for perioperative chemotherapy in European phase III studies, the phase III PRODIGY study (ClinicalTrials.gov identifier: NCT01515748) investigated whether neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 could improve outcomes versus standard treatment in Korean patients with resectable LAGC. PATIENTS AND METHODS: Patients 20-75 years of age, with Eastern Cooperative Oncology Group performance status 0-1, and with histologically confirmed primary gastric or gastroesophageal junction adenocarcinoma (clinical TNM staging: T2-3N+ or T4Nany) were randomly assigned to D2 surgery followed by adjuvant S-1 (40-60 mg orally twice a day, days 1-28 every 6 weeks for eight cycles; SC group) or neoadjuvant DOS (docetaxel 50 mg/m2, oxaliplatin 100 mg/m2 intravenously day 1, S-1 40 mg/m2 orally twice a day, days 1-14 every 3 weeks for three cycles) before D2 surgery, followed by adjuvant S-1 (CSC group). The primary objective was progression-free survival (PFS) with CSC versus SC. Two sensitivity analyses were performed: intent-to-treat and landmark PFS analysis. RESULTS: Between January 18, 2012, and January 2, 2017, 266 patients were randomly assigned to CSC and 264 to SC at 18 Korean study sites; 238 and 246 patients, respectively, were treated (full analysis set). Follow-up was ongoing in 176 patients at data cutoff (January 21, 2019; median follow-up 38.6 months [interquartile range, 23.5-62.1]). CSC improved PFS versus SC (adjusted hazard ratio, 0.70; 95% CI, 0.52 to 0.95; stratified log-rank P = .023). Sensitivity analyses confirmed these findings. Treatments were well tolerated. Two grade 5 adverse events (febrile neutropenia and dyspnea) occurred during neoadjuvant treatment. CONCLUSION: PRODIGY showed that neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, is effective and tolerable in Korean patients with LAGC.

The incidence of venous thromboembolism is not lowin Korean patients with advanced pancreatic cancer [corrected]

Background: Pancreatic cancer is among the most common malignancies associated with venous thromboembolism (VTE). Asian patients are known to have a lower incidence of VTE compared to Caucasian patients. However, few studies have investigated the incidence of VTE in Asian patients with pancreatic cancer. Methods: This retrospective review of medical records was performed on 505 patients with histopathologically proven advanced stage pancreatic cancer, from January 2006 to December 2012, at Soonchunhyang University Hospitals. Results: Ninety-four patients (18.6%) had at least one pulmonary embolism (PE), deep vein thrombosis (DVT), or splanchnic vein thrombosis (SVT); 38 patients had isolated SVT; and 56 patients (11.1%) had at least one classic VTE (PE and/or DVT of lower extremities). Patients with more advanced stages of pancreatic cancer (distant metastatic stage, recurrence) or who had received chemotherapy had a higher incidence of classic VTE. Patients who were simultaneously diagnosed with pancreatic cancer and classic VTE had a poorer prognosis than patients with subsequent VTEs. There was a significant difference in overall survival (OS) between the presence and absence of a concurrent classic VTE diagnosis (median: OS, 2.1 mo vs. 10.7 mo; P<0.001). Even when VTE included SVT, the result was similar (P<0.001). Conclusion: In Korean patients with advanced pancreatic cancer, the incidence of VTEs is comparable to that of Caucasian patients. We also found that pancreatic cancer patients with concurrent VTEs had a poor prognosis compared to patients who developed VTEs later.

Phase II study of palliative S-1 in combination with cisplatin as second-line chemotherapy for gemcitabine-refractory pancreatic cancer patients.

In this study, we examined the efficacy and toxicity of S-1 with cisplatin as a second-line palliative chemotherapy for gemcitabine-refractory pancreatic cancer patients. Patients who had been previously treated with gemcitabine-based chemotherapy as palliative first-line chemotherapy received S-1/cisplatin [body surface area (BSA) <1.25 m(2), S-1 40 mg/day; BSA ≤1.25 to <1.5 m(2), 50 mg/day; BSA ≥1.5 m(2) 60 mg/day, orally, bid, daily on days 1-14 followed by a 7-day washout and cisplatin 60 mg/m(2)/day intravenously on day 1] every three weeks. The enrollment of 32 patients was planned, but the study was terminated early, prior to the first stage, following the enrollment of 11 patients. The median age of the patients was 56 (range, 42-74) years. Nine patients had a performance status (PS) of one. In total, there were 21 chemotherapy cycles and the median treatment duration was 21 (range, 7-96) days. Of the 11 patients, five could not be evaluated due to discontinuation prior to the response evaluation. One of the six evaluable patients achieved stable disease (9.1% in intention to treat analysis and 16.7% in per-protocol analysis), while five had progressive disease. Grade 3-4 hematological toxicities were anemia in one, neutropenia in one and thrombocytopenia in one cycle. Grade 3-4 nonhematological toxicities were fatigue in three, nausea in four, anorexia in two, diarrhea in one and peripheral neuropathy in two cycles. With a median follow-up period of 8.9 (range, 3.2-11.3) months, the median time to progression was 44 days [95% confidence interval (CI) 25.4-62.6] and the median overall survival was 81 days (95% CI 9.3-152.7). Combination chemotherapy with S-1 and cisplatin as applied in this study did not result in promising antitumor activity, a high degree of toxicity and poor compliance.

Clinical and cost effectiveness of bevacizumab + FOLFIRI combination versus FOLFIRI alone as first-line treatment of metastatic colorectal cancer in South Korea.

BACKGROUND: Bevacizumab has been extensively investigated in combination with various standard chemotherapies in the treatment of metastatic colorectal cancer (mCRC). However, a comparison to irinotecan + infusional 5-fluorouracil/leucovorin (FOLFIRI) is lacking. OBJECTIVE: To explore clinical effectiveness and cost-effectiveness of adding bevacizumab to a regimen of FOLFIRI for the first-line treatment of mCRC in the Republic of Korea by conducting an indirect treatment comparison. METHODS: A health-economic model was developed to investigate the possible health outcomes (life-years gained [LYG]), direct costs, and incremental cost-effectiveness ratio (ICER) of adding bevacizumab to a FOLFIRI regimen. Data on progression-free and overall survival were derived from randomized clinical trials and were used in the indirect treatment comparison. The annual discount rate for costs and outcomes was 5%. A lifetime horizon of 8 years was used. Sensitivity analyses were carried out on all pivotal model assumptions. RESULTS: Incremental mean overall survival among patients treated with bevacizumab + FOLFIRI varied between 8.6 and 15.7 months compared with patients treated with FOLFIRI alone. The deterministic base-case result was 1.177 LYG. The discounted ICERs ranged from µ31.8 to µ39.5 million/LYG, with the base-case result being µ34.5 million/LYG. Treatment effect had the most impact on the outcomes in this model. CONCLUSIONS: Although there is no formal threshold for ICER per LYG in Korea, funding may be considered for bevacizumab + FOLFIRI, particularly if the severity and end-of-life nature of mCRC is taken into account.

Pathophysiological role of hormones and cytokines in cancer cachexia.

We investigated the role of fasting hormones and pro-inflammatory cytokines in cancer patients. Hormones (ghrelin, adiponectin, and leptin) and cytokines (TNF-α, IFN-γ, and IL-6) were measured by ELISA or RIA in lung cancer and colorectal cancer patients before the administration of cancer therapy, and measurements were repeated every 2 months for 6 months. From June 2006 to August 2008, 42 patients (19 with colorectal cancer and 23 with lung cancer) were enrolled. In total, 21 patients were included in the cachexia group and the others served as a comparison group. No significant difference in the initial adiponectin, ghrelin, TNF-α, IFN-γ, or IL-6 level was observed between groups, although 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.

Efficacy and safety of oxaliplatin, 5-Fluorouracil, and folinic Acid combination chemotherapy as first-line treatment in metastatic or recurrent gastric cancer.

PURPOSE: We retrospectively determined the efficacy and safety of the combination of oxaliplatin, 5-fluorouracil (5-FU), and folinic acid (FA) as first-line chemotherapy for patients with metastatic or recurrent gastric cancer. MATERIALS AND METHODS: Between January 2006 and August 2009, 39 patients with histologically-confirmed, metastatic or recurrent gastric cancer underwent chemotherapy, and the results were retrospectively investigated. The chemotherapy regimen consisted of oxaliplatin (100 mg/m(2)) and FA (200 mg/m(2); 2-hour infusion), then 5-FU (2,400 mg/m(2); 46-hour continuous infusion) every 2 weeks. RESULTS: Thirty-nine patients received a total of 210 treatment cycles. The median number of cycles was 6 (range, 1 to 16). Of the 32 evaluable patients, zero patients achieved a complete response and 11 patients achieved a partial response (response rate, 28.2%). The median time-to-progression and overall survival were 4.3 months (95% confidence interval [CI], 2.0 to 6.5 months) and 9.8 months (95% CI, 3.5 to 16.0 months), respectively. The main hematologic toxicity was anemia, which was observed in 119 cycles (56.7%). Grade 3/4 neutropenia was observed in 32 cycles (15.2%). The main non-hematologic toxicity was constipation, which was observed in 91 cycles (46.2%). Peripheral neuropathy occurred in 71 cycles (33.8%); all cases were grade 1 or 2. No treatment-related deaths were reported. CONCLUSION: This study showed that combination chemotherapy with oxaliplatin, 5-FU, and FA is an active and well-tolerated regimen as first-line treatment in patients with metastatic or recurrent gastric cancer.

Phase II Clinical Trial of Genexol® (Paclitaxel) and Carboplatin for Patients with Advanced Non-small Cell Lung Cancer.

PURPOSE: This phase II clinical trial was conducted to evaluate the activity and safety of a combination treatment of paclitaxel (Genexol®) plus carboplatin in patients with advanced non-small cell lung cancer. MATERIALS AND METHODS: Chemotherapy-naïve patients having histologically confirmed advanced or metastatic non-small cell lung cancer were enrolled. Genexol® was administered at 225 mg/m(2) intravenous (IV) infusion over 3 hours, followed by carboplatin (area under the concentration-time curve=6) IV on day 1 every 3 weeks. RESULTS: Twenty-eight patients were enrolled between January 2003 and January 2005. A total of 110 cycles of chemotherapy were given. The median number of chemotherapy cycles was 4. A total of 25 study patients were evaluable. On an intent-to-treat basis, there were ten partial responses (response rate 35.7%). The median time-to-progression was 3.2 months (95% confidence interval [CI], 1.5 to 4.9) and the median overall survival was 8.2 months (95% CI, 4.1 to 12.3). The main hematologic grade 3/4 toxicity was neutropenia, which was observed in 14 (50.0%) patients. The main non-hematologic toxicity was peripheral neuropathy, which was observed in 12 patients (42.9%). Grade 3/4 neuropathy occurred in 8 patients (28.6%) and three patients discontinued treatment because of neuropathy. CONCLUSION: In this trial, the combination of Genexol® and carboplatin showed significant activity as first line treatment for patients with advanced or metastatic non-small cell lung cancer. However, a modest dose reduction of Genexol® is needed due to sensory neuropathy.

Clinical outcome of gastric cancer patients with bone marrow metastases.

PURPOSE: The prognosis of gastric cancer patients with bone marrow metastases is extremely poor. The current study was conducted to evaluate the clinical outcomes of advanced gastric cancer patients with bone marrow metastases. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 26 advanced gastric cancer patients with bone marrow metastases who were treated at Soonchunhyang University Hospital between September 1986 and February 2009. RESULTS: The median age was 46 years (range, 24 to 61 years). All patients had poorly differentiated adenocarcinoma, including 17 signet ring cell carcinomas. The majority of the patients had thrombocytopenia, anemia, and elevated lactate dehydrogenase levels. Sixteen patients (61.5%) received palliative chemotherapy (median, 4 cycles; range, 1 to 13 cycles). The median overall survival after detection of bone marrow metastases for the cohort of patients was 37 days (95% confidence interval, 12.5 to 61.5 days). The median overall survival after detection of bone marrow involvement was 11 days in the best supportive care group (range, 2 to 34 days) and 121 days (range, 3 to 383 days) in the palliative chemotherapy group (p<0.001). The causes of death were tumor progression (11 patients, 45%), brain hemorrhage (6 patients, 25%), infection (5 patients, 21%), and disseminated intravascular coagulation (1 patient, 4%). There were no chemotherapy-related deaths. CONCLUSION: Palliative chemotherapy could be considered in advanced gastric cancer patients with bone marrow metastases as a treatment option.

Safety and effectiveness of central venous catheterization in patients with cancer: prospective observational study.

This study investigated the safety and effectiveness of each type of central venous catheters (CVC) in patients with cancer. We prospectively enrolled patients with cancer who underwent catheterization involving a subclavian venous catheter (SVC), peripherally inserted central venous catheter (PICC), or chemo-port (CP) in our department. From March 2007 to March 2009, 116 patients underwent 179 episodes of catheterization. A SVC was inserted most frequently (46.4%). Fifty-four complications occurred (30.1%): infection in 23 cases, malpositioning or migration of the tip in 18 cases, thrombosis in eight cases, and bleeding in five cases. Malpositioning or migration of the tip occurred more frequently with a PICC (P<0.001); infection occurred more often with a tunneled catheter (P=0.028) and was observed more often in young patients (P=0.023). The catheter life span was longer for patients with solid cancer (P=0.002) than for those with hematologic cancer, with a CP (P<0.001) than a PICC or SVC, and for an indwelling catheter with image guidance (P=0.014) than a blind procedure. In conclusion, CP is an effective tool for long term use and the fixation of tip is important for the management of PICC.

A case of type B lactic acidosis in acute leukemia.

Type B lactic acidosis is a rare condition in patients with solid tumors or hematological malignancies. Although there have been several theories to explain its mechanism, the exact cause of lactic acidosis remains to be discovered. Lactic acidosis is usually related to increased tumor burden in patients with malignancy. We experienced a case of lactic acidosis in a 39-year-old man who visited an emergency room because of dyspnea, and the cause of lactic acidosis turned out to be recurrent acute leukemia. Chemotherapy relieved the degree of lactic acidosis initially, but as the disease progressed, lactic acidosis became aggravated. Type B lactic acidosis can be a clinical presentation of acute exacerbation of acute leukemia.

Epidermal growth factor receptor intron 1 CA dinucleotide repeat polymorphism and survival of advanced gastric cancer patients treated with cetuximab plus modified FOLFOX6.

Cetuximab is a monoclonal antibody targeting epidermal growth factor receptor (EGFR). The present study investigated the association between germline genetic polymorphisms and the treatment outcome of cetuximab plus modified leucovovin, fluorouracil, and oxaliplatin (FOLFOX)6 chemotherapy in advanced gastric cancer (AGC). DNA from peripheral blood mononuclear cells of 38 patients enrolled in a phase II study of cetuximab plus modified FOLFOX6 were analyzed for 16 polymorphisms in eight genes (EGFR, epidermal growth factor, transforming growth factor-alpha (TGFA), thymidylate synthase, excision repair cross-complementation group 1, Xeroderma pigmentosum group D, and fragment c gamma receptors (FCGR)2A and 3A). The EGFR intron 1 CA repeat polymorphism was associated with survival. Twenty-one patients had low repeats (sum of both alleles or=38). Patients with low CA repeats had longer progression-free survival (adjusted hazard ratio [HR] 0.42 [95% confidence interval [CI] 0.19-0.96], P = 0.040) and overall survival (adjusted HR 0.40 [95% CI 0.16-0.99], P = 0.048) compared with patients with high CA repeats. In addition, the tumor EGFR expression was higher in patients with a lower number of CA repeats. The association between the CA repeat status and survival was not found in a separate cohort of AGC patients (n = 68) treated only with modified FOLFOX6. These results suggest that the EGFR intron 1 CA repeat polymorphism could be a useful, predictive biomarker of cetuximab efficacy in AGC and merits further investigation in randomized studies.

GnRH agonist therapy in a patient with recurrent ovarian granulosa cell tumors.

A 65-yr-old woman presented 17 yr status post-hysterectomy with bilateral ovarian salpingo-oophorectomy, attributable to ovarian cancer. She was admitted to our hospital, with multiple cystic liver masses and multiple large seeded masses in her abdomen and pelvic cavity. Histological examination of the pelvic masses demonstrated granulosa cell tumors. After two courses of systemic combination chemotherapy, with paclitaxel and carboplatin, the masses in the abdomen and pelvic cavity increased, and debulking surgery also failed because of peritoneal dissemination with severe adhesion. Finally, she underwent palliative radiotherapy for only the pelvic masses obstructing the urinary and GI tracts, and monthly hormonal therapy with a gonadotrophin-releasing hormone agonist; leuprorelin 3.75 mg IM. Subsequently, multiple masses beyond the range of the radiation as well as those within the radiotherapy field partially decreased. This partial response had been maintained for more than 8 months as of the last follow-up visit. Owing to its long and indolent course and the low metabolic rate of the tumors, advanced or recurrent granulosa cell tumor (GCT) requires treatment options beyond chemotherapy, surgery, and radiotherapy. Hormonal agents may provide another treatment option for advanced or recurrent GCT in those who are not candidates for surgery, chemotherapy, or radiotherapy.

Adenocarcinoma has an excellent outcome with pemetrexed treatment in Korean patients: a prospective, multicenter trial.

OBJECTIVE: This prospective multicenter study conducted by the Korean Cancer Study Group evaluated the efficacy and safety of pemetrexed in Korean patients with advanced non-small cell lung cancer (NSCLC) who had prior chemotherapy. PATIENTS AND METHODS: Patients with stage IIIB or IV NSCLC in whom prior chemotherapy failed received pemetrexed 500 mg/m(2) every 3 weeks with folic acid and vitamin B12 supplementation until disease progression or the development of intolerable toxicity. Eighty-one patients were enrolled. RESULTS: The overall response rate for 78 evaluable patients was 5.1% [95% confidence interval (CI) 1.4-12.6; partial response 4/78, no complete response]. The disease control rate including complete, partial response and stable disease was 46.2% (36/78, 95% CI 34.8-57.8). With a median 8.7 months follow-up, the median time to progression was 3.1 months (95% CI 1.17-5.03) and the median overall survival (OS) was 7.8 months (95% CI 5.19-10.35). The median OS for patients with adenocarcinoma histology was 18.7 months compared to 6.1 months for non-adenocarcinoma. In a multivariate analysis, Eastern Cooperative Oncology Group performance status 0-1 [hazards ratio (HR)=0.331, 95% CI 0.135-0.814] and adenocarcinoma (HR=0.504, 95% CI 0.283-0.899) were independent factors for prolongation of overall survival. CONCLUSIONS: Pemetrexed monotherapy has promising efficacy in patients with advanced NSCLC as a second-line therapy with less hematologic and non-hematologic toxicity, especially in those with adenocarcinoma histology.

A phase II study of gemcitabine in combination with oxaliplatin as first-line chemotherapy in patients with inoperable biliary tract cancer.

PURPOSE: The aim of this study is to investigate the efficacy and safety of gemcitabine and oxaliplatin combination chemotherapy as first-line therapy in patients with inoperable biliary tract cancer (BTC). METHODS: The treatment of this non-randomized phase II study consisted of gemcitabine 1,000 mg/m(2) intravenously (i.v.) on day 1 and oxaliplatin 85 mg/m(2) i.v. on day 2 every 2 weeks until disease progression, unaccep toxicity or patients' refusal. RESULTS: From Sept 2006 to Oct 2007, 40 patients were enrolled. In the ITT analysis, the objective response rate was 15.0% and the disease control rate was 52.5%. The median overall survival (95% CI) was 8.5 months (6.4-10.7) and the time to progression was 4.2 months (0.5-7.9). For the 305 cycles, observed grade 3/4 toxicity was uncommon. CONCLUSIONS: Gemcitabine and dose adjusted oxaliplatin combination chemotherapy had moderate anti-tumor activity and was well tolerated as a first-line treatment for patients with inoperable BTC.

Mixed testicular germ cell tumor presenting as metastatic pure choriocarcinoma involving multiple lung metastases that was effectively treated with high-dose chemotherapy.

Choriocarcinoma in the testis is very rare, and it represents less than 1% (0.3%) of all the testicular germ cell tumors. It is a particularly aggressive variant of non-seminoma tumor, which is characterized by a high serum beta-HCG level and multiple lung metastases. The optimal management for this disease remains undefined. We report here on a case of choriocarcinoma with multiple lung metastases, and the patient has achieved continuous remission for 2 years after combination chemotherapy of BEP (bleomycin, etoposide and cisplatin) and sequential high-dose chemotherapy with autologous peripheral stem cell rescue.

Sulindac enhances arsenic trioxide-mediated apoptosis by inhibition of NF-kappaB in HCT116 colon cancer cells.

To study whether the apoptotic effect of arsenic trioxide (As2O3) on colon cancer cells could be enhanced by the addition of sulindac, HCT116 cells were treated with As2O3 (1, 5, 10 microM) and sulindac (0.5 mM), either alone or in combination. As2O3 alone slightly inhibited the growth of HCT116 cells, whereas the combination of As2O3 and sulindac reduced cell growth by 30-40%. Annexin V staining indicated that the synergistic effect of the combination was mediated through increased apoptosis. We examined whether the combination of As2O3 and sulindac on apoptosis is mediated by inhibition of the NF-kappaB pathway in HCT116 colon cancer cells. Western blot analysis showed that the level of nuclear NF-kappaB (p65) was not changed significantly by As2O3 or sulindac treatment alone, while the level of nuclear NF-kappaB (p65) was drastically decreased in the combination treatment by inhibiting the phosphorylation and the degradation of IkappaB-alpha. These results suggest that sulindac enhances apoptosis when combined with As2O3 by inhibiting NF-kappaB activation mediated through the blocking of phosphorylation and degradation of IkappaB-alpha.

Phase II trial of gemcitabine combined with cisplatin in patients with inoperable biliary tract carcinomas.

OBJECTIVES: The aim of this phase II study was to evaluate the response rate to gemcitabine combined with cisplatin in patients with locally advanced, metastatic or recurrent biliary tract cancer who had received no prior chemotherapy. METHODS: The treatment consisted of cisplatin 70 mg/m(2) in intravenous infusion followed by gemcitabine 1,250 mg/m(2) in 30-min intravenous infusion on days 1 and 8, repeated every 3 weeks until disease progression, unacceptable toxicity, patient's refusal or up to 8 cycles. RESULTS: Thirty-nine patients with advanced biliary cancer were enrolled between March 2003 and August 2003. Fourteen patients (40%) had gall bladder cancer and 20 patients (57%) had cholangiocarcinoma. Thirty-two patients (91%) had metastatic disease at study entry with liver being the most commonly involved site of metastasis. About 84.5 and 94.2% of the initially planned dose were administered for gemcitabine and cisplatin, respectively. In the ITT population (n = 35), six partial responses were observed for an objective response rate of 17.1% (95% CI; 4.7-29.6%). Ten patients (28.6%) had stable disease, 16 (45.7%) progressed, and three (8.6%) were not evaluable. For the 35 patients in the ITT population, the median overall survival time was 8.6 months (95% CI; 6.1-10.4 months). The median time to disease progression was 3.2 months (95% CI; 2.3-4.9 months) and the median time to treatment failure was 3.1 months (95% CI; 1.9-4.1 months). Among the six tumor responders, the median duration of tumor response was 7.3 months (95% CI; 5.6-11.0 months). The most common grade 3/4 maximum toxicities were nausea (3.4%) and vomiting (2.7%). CONCLUSION: The combination chemotherapy with gemcitabine and cisplatin in this trial demonstrated moderate antitumor activity with favorable toxicity profile.

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.

Phase II study of docetaxel and cisplatin as first-line chemotherapy in patients with recurrent or metastatic gastric cancer.

PURPOSE: Palliative chemotherapy for patients with recurrent or metastatic gastric cancer has been shown to have a survival benefit. Docetaxel monotherapy has achieved appreciable results for treating gastric cancer. We investigated the clinical efficacy and feasibility of a docetaxel and cisplatin combination regimen for patients suffering with recurrent or metastatic gastric cancer. MATERIALS AND METHODS: Patients with histologically proven, bidimensionally measurable lesions of recurrent or metastatic gastric cancer, and they had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 and no prior palliative chemotherapy were eligible for this study. The combination chemotherapy regimen consisted of docetaxel 75 mg/m(2) plus cisplatin 75 mg/m(2) on day 1, and this was repeated every 3 weeks until disease progression. RESULTS: 32 patients were enrolled from 2002 to 2005. The objective response rate was 31.3% (95% confidence interval (CI): 14.2 approximately 48.2%) with no CR. The disease control rate was 59.4%. At a median follow up of 38.9 months, the median overall survival was 7.4 months (95% CI: 6.3 approximately 8.5). The median time to progression was 4.7 months (95% CI: 3.1 approximately 6.3). During a total of 106 cycles, grade 3 or 4 hematological toxicities were observed as follows: neutropenia (39 of 106 cycles) and anemia (3 of 106 cycles). The grade 3 or 4 non-hematological toxicities included anorexia (18.9%) and nausea/vomiting (21.7%). CONCLUSION: Docetaxel and cisplatin combination chemotherapy showed promising anti-tumor activity and this was well tolerated as a first-line treatment for patients with recurrent or metastatic gastric cancer. Further large, randomized phase III studies are warranted.