AIM: To determine the efficacy of bevacizumab in patients with metastatic colorectal cancer (MCRC) who have failed prior chemotherapy without bevacizumab.
METHODS: Between March 2002 and June 2010, 40 patients in South Korea with MCRC who were treated with bevacizumab plus chemotherapy as a second or later-line treatment were analyzed retrospectively for their overall response rate (ORR), overall survival (OS), and progression-free survival (PFS). The tumor responses were assessed using the Response Evaluation Criteria in Solid Tumors guidelines.
RESULTS: All of the patients had progressed under prior chemotherapy without bevacizumab. Three patients (7.5%) exhibited an ORR, twenty one patients (52.5%) exhibited stable disease (SD), and fifteen patients (37.5%) exhibited disease progression. The median duration of the OS and PFS were 14.0 mo and 6.13 mo respectively. The median OSs were 16.60, 14.07 and 13.00 mo for second-line, third-line and fourth- or later-line treatments, respectively. The median PFSs were 7.23, 7.30 and 3.87 mo for the second-line, third-line and fourth- or later-line treatments, respectively.
CONCLUSION: In patients with MCRC, bevacizumab combined chemotherapy may be beneficial during second- or later-line treatment.
Colorectal cancer; Metastasis; Bevacizumab; Efficacy; Second- or later-line
To evaluate the efficacy of hydromorphone-OROS (HM-OROS) in reducing sleep disturbance and relieving cancer pain.
Materials and Methods
One hundred twenty cancer patients with pain (numeric rating scale [NRS] ≥ 4) and sleep disturbance (NRS ≥ 4) were evaluated. The initial HM-OROS dosing was based on previous opioid dose (HM-OROS:oral morphine=1:5). Dose adjustment of the study drug was permitted at the investigator’s discretion. Pain intensity, number of breakthrough pain episodes, and quality of sleep were evaluated.
A total of 120 patients received at least one dose of HM-OROS; 74 of them completed the final assessment. Compared to the previous opioids, HM-OROS reduced the average pain NRS from 5.3 to 4.1 (p < 0.01), worst pain NRS from 6.7 to 5.4 (p < 0.01), sleep disturbance NRS from 5.9 to 4.1 (p < 0.01), incidence of breakthrough pain at night from 2.63 to 1.53 times (p < 0.001), and immediate-release opioids use for the management of breakthrough pain from 0.83 to 0.39 times per night (p = 0.001). Of the 74 patients who completed the treatment, 83.7% indicated that they preferred HM-OROS to the previous medication. The adverse events (AEs) were somnolence, asthenia, constipation, dizziness, and nausea.
HM-OROS was efficacious in reducing cancer pain and associated sleep disturbances. The AEs were manageable.
Cancer pain; Sleep disturbance; Hydromorphone-OROS (HM-OROS)
Follicular dendritic cells (FDC) are non-lymphoid, non-phagocytic accessory cells of the immune system and these cells are essential for antigen presentation and regulation of the reactions in germinal centers. Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm that shows a low-to-intermediate malignant potential. The most commonly involved sites are the lymph nodes, but FDCS may also occur at a variety of extranodal sites, including the oral cavity, tonsils, gastrointestinal tract and liver. We describe here a 79-year-old woman who had FDCS with extensive lymph node involvement, dry cough, and an itching sensation. The patient improved after systemic chemotherapy.
Dendritic cell sarcoma; Follicular; Dendritic cells; Lymph nodes
Mycoflora was assessed in the commercial meju from four well-separated geographic origins. A total of 112 fungal isolates were identified by phenotypic characteristics and molecular taxonomy using sequencing the internal transcribed spacer of the rDNA and revealed 19 species from 13 genera. Enzymatic characteristics of protease and amylase, and mycotoxin production were analyzed.
Amylase; Meju; Mycoflora; Mycotoxin; Protease
Arsenic trioxide (As2O3) is a well-known and effective treatment that can result in clinical remission for patients diagnosed with acute promyelocytic leukemia (APL). The biologic efficacy of As2O3 in APL and solid tumor cells has been explained through its actions on anti-proliferation, anti-angiogenesis, and apoptotic signaling pathways. We theorize that As2O3 activates a pathway that disrupts microtubule dynamics forming abnormal, nonfunctioning mitotic spindles, thus preventing cellular division. In this study, we investigated how As2O3 induces apoptosis by causing microtubule dysfunction.
Cultured NB4 cells were treated with As2O3, paclitaxel, and vincristine. Flow cytometric analysis was then performed. An MTT assay was used to determine drug-mediated cytotoxicity. For tubulin polymerization assay, each polymerized or soluble tubulin was measured. Microtubule assembly-disassembly was measured using a tubulin polymerization kit. Cellular microtubules were also observed with fluorescence microscopy.
As2O3 treatment disrupted tubulin assembly resulting in dysfunctional microtubules that cause death in APL cells. As2O3 markedly enhanced the amount of depolymerized microtubules. The number of microtubule posttranslational modifications on an individual tubulin decreased with As2O3 concentration. Immunocytochemistry revealed changes in the cellular microtubule network and formation of polymerized microtubules in As2O3-treated cells.
The microtubules alterations found with As2O3 treatment suggest that As2O3 increases the depolymerized forms of tubulin in cells and that this is potentially due to arsenite's negative effects on spindle dynamics.
Acute promyelocytic leukemia; Arsenic trioxide; Tubulin; Apoptosis; Antimitotic agents
The objectives of the present study were to evaluate the efficacy and safety of an outpatient-basis chemotherapy of oxaliplatin, 5-fluorouracil, and leucovorin as the first-line treatment for patients with advanced colorectal cancer. Forty-three histologically confirmed patients with metastatic or recurrent colorectal cancer were enrolled. The chemotherapy consisted of oxaliplatin 85 mg/m2 as a 2-hr infusion on day 1, plus leucovorin 30 mg/m2 over 10 min, followed by bolus 5-fluorouracil 400 mg/m2 and an 8-hr infusion of 5-fluorouracil 600 mg/m2 on days 1 and 2 (modified FOLFOX4), all of which were administered on an outpatient basis every 2 weeks. The median age was 58 yr (range 33-72 yr), and 25 (58.1%) patients had metastatic diseases. Eventually, 39 patients were assessable for efficacy and all assessable for toxicity. Four (9.3%) complete responses and 11 (25.6%) partial responses were confirmed, giving an overall response rate of 34.9% (95% CI; 20.0-49.7%). The median time to progression and median overall survival for all patients was 6.1 months and 17.4 months, respectively. Grade 3/4 neutropenia occurred in 2 patients (4.7%) and febrile neutropenia was observed in 1 patient (2.3%). Modified FOLFOX4, an outpatient-basis regimen, was found to be well-tolerated and effective as the first-line chemotherapy in patients with advanced colorectal cancer.
Colorectal Neoplasms; Oxaliplatin; Fluorouracil; Leucovorin
Malignant melanoma of the lacrimal sac is very rare and primary malignant melanoma is extremely rare. It is usually diagnosed at an advanced stage after excision or biopsy of a tumor. We treated a patient with tearing and bloody discharge from the left eye. We performed a dacryocystectomy with the suspicion of a chronic dacryocystitis. However, the pathological findings and the immunohistochemical studies showed a malignant melanoma of the lacrimal sac. The patient underwent postoperative irradiation therapy. Follow up two months after surgery revealed no evidence of recurrence.
Early diagnosis is very important for prognosis in patients with malignant melanoma of the lacrimal sac. Because this tumor often presents with symptoms similar to dacryocystitis and may masquerade as a chronic dacryocystitis, it can be difficult to make an early diagnosis.
Malignant melanoma; Lacrimal apparatus; Dacryocystitis
Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-fluorouracil (5-FU). Thus, patients with a DPD deficiency are at risk of developing severe 5-FU-associated toxicity.
A 37-year-old female with gastric cancer underwent a curative operation, followed by adjuvant chemotherapy consisting of 5-FU and epirubicin. After the first cycle of chemotherapy, the patient manifested grade 2 mucositis and febrile neutropenia, and when her treatment was subsequently continued with doxifluridine she developed severe mucositis and febrile neutropenia. A PCR study revealed that her DPD mRNA level was lower than that in a control group. Thus, when considering the routine use of 5-FU for the treatment of cancer patients, an analysis of DPD activity or screening for DPD mutations is warranted in confined patients who experience unpredicted severe toxicity after initial 5-FU administration, even though DPD deficiency is a rare metabolic defect.
Dihydrouracil dehydrogenase; Fluorouracil; Stomach neoplasms
Thrombocytopenia (TP) is a frequent complication after allogeneic stem cell transplantation (SCT) and regarded as a poor prognostic factor, especially in patients with chronic graft-versus-host disease (GVHD), although various factors were related to the development of TP after allogeneic SCT. Sixty-three patients receiving allogeneic peripheral blood stem cell transplantation (PBSCT) were stratified according to platelet count (PC) at day +60 and analyzed in terms of overall survival (OS) and the incidence of non-relapse mortality (NRM). Ten patients (15.9%) were stratified in group 1 (PC ≤29×109/L), 23 patients (36.5%) in group 2 (PC 30-79×109/L), and 30 patients in group 3 (PC ≥80×109/L). Group 3 was associated with lower incidence of extensive chronic GVHD (p=0.013), better 3-yr OS (p=0.0030), and lower NRM rate (p<0.0001). In multivariate analyses, the PC at day +60 was identified as an independent prognostic factor (p=0.003) together with CD34+ cell dose (p<0.001), disease risk (p=0.004), and acute GVHD (p=0.033) in terms of NRM, and the PC (p=0.047) and CD34+ cell dose (p=0.026) in terms of incidence of infectious events. Measuring the platelet count at day +60 is a simple method for predicting the risk of chronic GVHD development and prognosis after allogeneic PBSCT.
Thrombocytopenia; Transplantation, Homologous; Allogeneic; Peripheral Blood Stem Cell Transplantation; Mortality; Opportunistic Infections
The current phase II study was conducted to evaluate the response rate and safety of a combination regimen of biweekly irinotecan plus cisplatin in pretreated patients with advanced gastric cancer. Patients with previously treated metastatic or recurrent gastric cancer received intravenous irinotecan 70 mg/m2 and cisplatin 30 mg/m2 on day 1 and 15 every 4-week cycle. Thirty-two patients were enrolled in the current study. Of these, 31 patients were assessable for efficacy and all for toxicity. No complete response and 5 partial responses were confirmed, giving an overall response rate of 15.6% (95% CI; 2.3-28.9%). The median time to progression and median overall survival for all patients was 113 days and 184 days, respectively. Grade 3/4 neutropenia occurred in 6 patients (18.8%), yet no febrile neutropenia was observed. In addition, grade 3 anorexia was observed in 4 patients (12.5%) and grade 3 diarrhea occurred in 2 patients (6.2%). The combination chemotherapy of biweekly irinotecan and cisplatin was found to be moderately effective and well tolerated in pretreated patients with advanced gastric cancer. Accordingly, this regimen can be regarded as an important second-line treatment option for advanced gastric cancer.
irinotecan; Cisplatin; Drug Therapy; Stomach Neoplasms
We conducted a multi-center, phase II trial to evaluate the efficacy and safety of using Padexol (a paclitaxel formulation) combined with cisplatin for the patients suffering with advanced gastric adenocarcinoma.
Materials and Methods
39 patients (median age: 60 years; males: 90%) who were diagnosed with advanced gastric cancer were enrolled from 5 hospitals. Padexol 175 mg/m2 was administered as a 3-hr infusion, and this was followed by cisplatin 75 mg/m2 as an intravenous infusion on day 1, once every 3 weeks.
Out of these 39 patients, 34 patients were assessable for treatment efficacy and 39 patients were assessable for the toxicity. Objective responses occurred in 13 patients (33%); 1 patient (3%) had a complete response and 12 patients (31%) had partial responses. 6 patients (15%) achieved a stable disease state. The median duration of response was 7.1 months, and the median time to progression and the overall survival were 4.8 months and 6.7 months, respectively. The major treatment-related adverse events were hematologic toxicity, including WHO grade 3 or 4 neutropenia in 13 patients (33%). However, febrile neutropenia occurred in only 1 patient and the non-hematologic toxicity was usually mild.
The combination of Padexol and cisplatin was found to be active and it seems to be a relatively well-tolerated regimen for the treatment of advanced gastric cancer.
Padexol™; Paclitaxel; Cisplatin; Stomach neoplasms
The main objectives of the current study were to evaluate the efficacy and safety of a CEOP-E regimen for patients with aggressive non-Hodgkin's lymphoma (NHL). Fifty-one consecutive patients with newly diagnosed aggressive NHL were enrolled in the study. Median age of patients was 57 (range, 18-75) yr old, and male to female ratio was 1.32:1. Diffuse large B cell lymphoma (68.8%) was the most common histological subtype. Thirty patients (58.8%) had Ann Arbor stage III or IV diseases at diagnosis. One course of chemotherapy consisted of an intravenous combination of cyclophosphamide 750 mg/m2, epirubicin 50 mg/m2, vincristine 2 mg, etoposide 80 mg/m2 on day 1 and oral administration of 100 mg prednisone on days 1 to 5 (CEOP-E). A complete response or unconfirmed complete response was achieved in 31 (63.3%) out of 49 evaluated patients. With a median follow-up of 16.3 months, 26 events including relapse and death were observed. The estimated 2-yr survival rate for all patients and disease free survival rate for patients achieving complete re-sponse was 58.9% and 57.1%, respectively. Episodes of febrile neutropenia occurred in 5 (10.2%) patients. Transient episodes of ECG abnormality (1st degree AV block) were observed in 2 patients. Accordingly, the CEOP-E regimen produced comparable results to those of other regimens, including CHOP, in terms of the response rate and overall survival. The current regimen seemed to minimize the cardiac toxicity due to an accumulated dose of anthracycline in the treatment of aggressive NHL.
Lymphoma, Non-Hodgkin; Drug Therapy; CEOP-E Regimen; Cyclophosphamide; Epirubicin, Vincristine; Prednisone; Etoposide