No abstract available.
Organoplatinum Compounds

OBJECTIVE: The concept of platinum sensitivity and cross-resistance among platinum agents are widely known in the management of recurrent ovarian cancer. The aim of this study was to evaluate two hypotheses regarding the validity of the concept of platinum sensitivity and non-cross-resistance of cisplatin analogue with cisplatin in recurrent cervical cancer. METHODS: In this retrospective study, the clinical data of patients with recurrent cervical cancer, who had a history of receiving cisplatin based chemotherapy (including concurrent chemoradiotherapy [CCRT] with cisplatin) and who received second-line chemotherapy at the time of recurrence between April 2004 and July 2012 were reviewed. RESULTS: In total, 49 patients-34 squamous cell carcinomas (69.4%) and 15 non-squamous cell carcinomas (30.6%)-were enrolled. The median age was 53 years (range, 26 to 79 years). Univariate and multivariate analysis showed that a platinum free interval (PFI) of 12 months has a strong relationship with the response rate to second-line chemotherapy. Upon multivariate analysis of survival after second-line platinum-based chemotherapy, a PFI of 12 months significantly influenced both progression-free survival (hazard ratio [HR], 0.349; 95% confidence interval [CI], 0.140 to 0.871; p=0.024) and overall survival (HR, 0.322; 95% CI, 0.123 to 0.842; p=0.021). In patients with a PFI of less than 6 months, the difference of progression-free survival between patients with re-administration of cisplatin (3.0 months) and administration of cisplatin analogue (7.2 months) as second-line chemotherapy was statistically significant (p=0.049, log-rank test). CONCLUSION: The concept of platinum sensitivity could be applied to recurrent cervical cancer and there is a possibility of noncross-resistance of cisplatin analogue with cisplatin.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Carboplatin/administration & dosage ; Carcinoma, Squamous Cell/*drug therapy/mortality ; Cisplatin/administration & dosage/*analogs & derivatives ; Drug Resistance, Neoplasm ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Recurrence, Local/*drug therapy ; Organoplatinum Compounds/administration & dosage ; Retreatment ; Retrospective Studies ; Treatment Outcome ; Uterine Cervical Neoplasms/*drug therapy/mortality

OBJECTIVE: Epithelial cell adhesion molecule (EpCAM) has experienced a renaissance lately as a binding site for targeted therapy as well as a prognostic marker in epithelial malignancies. Aim of this study was to study EpCAM as a potential prognostic marker in epithelial ovarian cancer (EOC). METHODS: EpCAM expression was assessed by immunohistochemistry on paraffin-embedded primary EOC-tissue samples. EpCAM overexpression was defined as an expression of EpCAM of 76% to 100%. Tissue samples and clinical data were systematically collected within the international and multicenter "Tumorbank Ovarian Cancer" network. RESULTS: Seventy-four patients, diagnosed with EOC between 1994 and 2009, were included in the study (median age, 56 years; range, 31 to 86 years). The majority of the patients (81.1%) presented with an advanced stage International Federation of Gynecology and Obstetrics (FIGO) III/IV disease. Histology was of the serous type in 41 patients (55.4%), endometrioid in 19 (25.6%), and mucinous in 14 (19%). EpCAM was overexpressed in 87.7%. Serous tumors overexpressed EpCAM significantly more often than mucinous tumors (87.8% vs. 78.6%, p=0.045); while no significant difference was noted between the other histological subgroups. EpCAM overexpression was significantly associated with a better progression free survival and higher response rates to platinum based chemotherapy (p=0.040 and p=0.048, respectively). EpCAM was identified as an independent prognostic marker for overall survival (p=0.022). CONCLUSION: Our data indicate a significant association of EpCAM overexpression with a more favorable survival in EOC-patients. Serous cancers showed a significant EpCAM overexpression compared to mucinous types. Larger multicenter analyses are warranted to confirm these findings.
Adult ; Aged ; Aged, 80 and over ; Antigens, Neoplasm/*metabolism ; Antineoplastic Agents/*therapeutic use ; Carboplatin/therapeutic use ; Cell Adhesion Molecules/*metabolism ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Proteins/metabolism ; Neoplasm Staging ; Neoplasms, Glandular and Epithelial/*diagnosis/drug therapy/pathology ; Organoplatinum Compounds/*therapeutic use ; Ovarian Neoplasms/*diagnosis/drug therapy/pathology ; Paclitaxel/therapeutic use ; Prognosis ; Tissue Banks ; Treatment Outcome ; Tumor Markers, Biological/*metabolism

OBJECTIVETo screen the sensitive chemotherapeutic agents to human endometrial carcinoma cell line-1 (HECCL-1) and study its mechanism.

METHODSMTT method was used to examine the relative inhibition ratios (RIRs) of various concentrations of 18 chemotherapeutic agents to HECCL-1. Cell cycle, apoptosis and expression of MDR1 protein were detected by FCM.

RESULTSNine of the chemotherapeutic agents studied obviously inhibited the proliferative activity of HECCL-1 in a dose-dependent manner. The order of sensitivity was as follows: adriamycin (ADM), oxaliplatin (L-OHP), carboplatin (CBP), cisplatin (DDP), taxol (TAL), epirubicin (EPI), mitoxantrone (MIT), dactomycin (ACTD) and 5-fluorouracil (5-Fu). FCM showed these agents could significantly reduce the proportion of cells in G0-G1 phase, and increase the proportion of cells in S and G2-M phase (P < 0.05). Cell apoptosis was observed in 11 chemotherapeutic agents at their peak concentration. MDR expression was induced after using EPI, 5-Fu, hydroxycamptothecin (HCPT) and MIT.

CONCLUSIONHECCL-1 is sensitive to a number of the chemotherapeutic agents studied. Induced apoptosis may be the major mechanism of drug sensitivity, and acquired drug-resistance may be the critical reason against continued administration.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Antineoplastic Agents ; administration & dosage ; pharmacology ; Apoptosis ; drug effects ; Carboplatin ; administration & dosage ; pharmacology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Doxorubicin ; administration & dosage ; pharmacology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Endometrial Neoplasms ; metabolism ; pathology ; Epirubicin ; administration & dosage ; pharmacology ; Female ; Fluorouracil ; administration & dosage ; pharmacology ; Humans ; Organoplatinum Compounds ; administration & dosage ; pharmacology

PURPOSE: Peritoneal carcinomatosis (PC) of colorectal cancer (CRC) is common and is the second most common cause of death. Clinical studies regarding chemotherapy for CRC with PC have been classically rather limited in scope. We evaluated the efficacy of modified oxaliplatin, leucovorin, and fluorouracil (m-FOLFOX4) regimen for PC of CRC origin. MATERIALS AND METHODS: CRC patients with PC were treated with cycles of oxaliplatin at 85 mg/m2 on day 1, leucovorin 20 mg/m2 followed by 5-fluorouracil (5-FU) via a 400 mg/m2 bolus and a 22 hours continuous infusion of 600 mg/m2 5-FU on days 1-2 at 2-week intervals. RESULTS: Forty patients participated in this study. Median age was 55 years. Thirty-two patients (80.0%) received previous operation, and 60.0% of PC occurred synchronously. Thirty-five patients (87.5%) were assessable and exhibited measurable lesions. Two patients (5.7%) demonstrated complete response and five patients (14.3%) showed partial response. The median time to progression was 4.4 months (95% confidence interval, 2.5 to 6.3 months), the median overall survival time was 21.5 months (95% confidence interval, 17.2 to 25.7 months). There was no treatment related death. Presence of liver metastasis (p=0.022), performance status (p=0.039), and carcinoembryonic antigen level (p=0.016) were related to the time to progression. Patients with low carcinoembryonic antigen level (37.2 months vs. 15.6 months, p=0.001) or good performance status (22.5 months vs. 6.8 months, p=0.040) showed better overall survival. CONCLUSION: The m-FOLFOX4 regimen was determined to be effective for CRC patients with PC.
Carcinoembryonic Antigen ; Carcinoma ; Cause of Death ; Colorectal Neoplasms ; Fluorouracil ; Humans ; Leucovorin ; Liver ; Neoplasm Metastasis ; Organoplatinum Compounds ; Peritoneum

PURPOSE: This study was designed to determine the efficacy and safety of FOLFOX-4 chemotherapy as a salvage treatment for patients with advanced gastric cancer (AGC). MATERIALS AND METHODS: The AGC patients with an ECOG performance status of 0~1 and progressive disease after prior treatments were registered onto this phase II trial. The patients received oxaliplatin (85 mg/m2 on day 1), leucovorin (200 mg/m2 on days 1 and 2) and 5-fluorouracil (400 mg/m2 as a bolus and 600 mg/m2 as a 22-hour infusion on days 1 and 2) every 2 weeks. RESULTS: For the 42 treated patients, a total of 228 chemotherapy cycles (median: 5, range: 1~12) were administered. Twenty-nine patients (69%) received FOLFOX-4 chemotherapy as a third-(50%) or fourth-line (19%) treatment. On the intent-to-treat analysis, 9 patients (21%) achieved a partial response, which was maintained for 4.6 months. The median progression-free survival and overall survival were 3.0 months and 6.2 months, respectively. The frequently encountered toxicities were neutropenia and gastrointestinal side effects, including anorexia. Although there was one possible treatment-related death, the toxicity profiles were generally predictable and manageable. CONCLUSION: Salvage chemotherapy with FOLFOX-4 is an effective and tolerable regimen for those heavily pretreated AGC patients who have a good performance status.
Anorexia ; Disease-Free Survival ; Drug Therapy, Combination ; Fluorouracil ; Humans ; Leucovorin ; Neutropenia ; Organoplatinum Compounds ; Stomach Neoplasms

PURPOSE: Little is known about outcomes in the use of third-line chemotherapy in cases of advanced gastric cancer (AGC). The primary aim of this retrospective study was to evaluate outcomes of docetaxel-based chemotherapy in patients with AGC that progressed after both oxaliplatin-based and irinotecan-based regimens. MATERIALS AND METHODS: Eligible patients were those with AGC who had previous chemotherapy including fluoropyrimidine and oxaliplatin as well as fluoropyrimidine and irinotecan and who received subsequent docetaxel-based chemotherapy. Thirty-five patients were retrospectively recruited from 5 medical centers in Korea. Patients received either weekly or 3 weekly with docetaxel +/- cisplatin. RESULTS: Thirty-one out of 35 patients were evaluated for treatment response. A total of 94 cycles of chemotherapy (median, 2; range, 1 to 7) were administered. The overall response rate was 14.3%, and the disease control rate was 45.7%. The median progression-free survival (PFS) was 1.9 months (95% confidence interval [CI], 1.1 to 2.7 months). The median overall survival (OS) was 3.6 months (95% CI, 2.8 to 4.4 months). PFS and OS were significantly prolonged in patients of the Eastern Cooperative Oncology Group, with performance status of 0 or 1 in multivariate analysis (PFS: hazard ratio[HR], 0.411; 95% CI, 0.195 to 0.868; p=0.020 and OS: HR, 0.390; 95% CI, 0.184 to 0.826; p=0.014, respectively). Four of the 35 patients enrolled in the study died due to infection associated with neutropenia. CONCLUSION: Our findings suggest that salvage docetaxel-based chemotherapy is a feasible treatment option for AGC patients with good performance status (PS), whereas chemotherapy for patients with poor PS (PS< or =2) should be undertaken with caution for those who previously failed oxaliplatin- and irinotecan-based regimens.
Camptothecin ; Disease-Free Survival ; Humans ; Korea ; Multivariate Analysis ; Organoplatinum Compounds ; Retrospective Studies ; Stomach Neoplasms ; Taxoids

The FOLFOX-4 regimen as first-line treatment in patients with advanced gastric cancer has not evidence of category 1 for prolongation of survival in patients with advanced gastric cancer. Therefore, the use is preferred in the second line. But, especially in elderly patients, FOLFOX regimen was active and well tolerated with lower toxicities. Further phase III study is warranted to evaluate the evidence for prolongation of survival in elderly patients or combination therapy with target agents in advanced gastric cancer.
Aged ; Antineoplastic Combined Chemotherapy Protocols ; Drug Therapy, Combination ; Fluorouracil ; Humans ; Leucovorin ; Organoplatinum Compounds ; Stomach Neoplasms

Although the relationship between malignancy risk with systemic sclerosis (SSc) has been inconclusive, there are some previous studies for a positive correlation. Most patients with SSc have some degree of lung parenchymal involvement in the form of interstitial thickening and fibrosis. Interstitial lung disease is the most common pulmonary manifestation of SSc. Interstitial lung disease following chemotherapy (5-fluorouracil, leucovorin, and oxaliplatin [FOLFOX]) is an uncommon life-threatening complication and it is induced by oxaliplatin. We report a case of multiple cancers in a patient with SSc and aggravated interstitial lung disease by chemotherapy.
Fibrosis ; Humans ; Leucovorin ; Lung ; Lung Diseases, Interstitial ; Lung Neoplasms ; Organoplatinum Compounds ; Scleroderma, Systemic

Most brachytherapy treatment planning systems employ a dosimetry formalism based on the AAPM TG-43 report which does not appropriately consider tissue heterogeneity. In this study we aimed to set up a simple Monte Carlo-based intracavitary high-dose-rate brachytherapy (IC-HDRB) plan verification platform, focusing particularly on the robustness of the direct Monte Carlo dose calculation using material and density information derived from CT images. CT images of slab phantoms and a uterine cervical cancer patient were used for brachytherapy plans based on the Plato (Nucletron, Netherlands) brachytherapy planning system. Monte Carlo simulations were implemented using the parameters from the Plato system and compared with the EBT film dosimetry and conventional dose computations. EGSnrc based DOSXYZnrc code was used for Monte Carlo simulations. Each (192)Ir source of the afterloader was approximately modeled as a parallel-piped shape inside the converted CT data set whose voxel size was 2x2x2 mm3. Bracytherapy dose calculations based on the TG-43 showed good agreement with the Monte Carlo results in a homogeneous media whose density was close to water, but there were significant errors in high-density materials. For a patient case, A and B point dose differences were less than 3%, while the mean dose discrepancy was as much as 5%. Conventional dose computation methods might underdose the targets by not accounting for the effects of high-density materials. The proposed platform was shown to be feasible and to have good dose calculation accuracy. One should be careful when confirming the plan using a conventional brachytherapy dose computation method, and moreover, an independent dose verification system as developed in this study might be helpful.
Accounting ; Brachytherapy ; Film Dosimetry ; Humans ; Monte Carlo Method ; Organoplatinum Compounds ; Population Characteristics ; Uterine Cervical Neoplasms ; Water