No abstract available.
Organoplatinum Compounds

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

Colorectal cancer represents a major public health problem in worldwide including Korea. According to the National Cancer Registry, colon cancer is the third most common cancer and the forth leading cause of cancer death. The surgery is a main treatment option for cure. Despite curative surgery in those presenting early, the risk of relapse is significantly high. To improve the survival, huge advances have been made in the treatment of colon cancer over the last decade. Especially, the median overall survival time for stage IV colon cancer has been reached from 6-9 months to over 20 months. Based on these results, drugs such as irinotecan, oxaliplatin and oral fluoropyrimidine have been used to evaluate the efficacy in adjuvant setting. Oxaliplatin based chemotherapy is now emerging as the standard of care in adjuvant treatment of stage III colon cancer. Targeted agents, which have shown promise in the metastatic setting, are currently being examined in the adjuvant setting, although results have been disappointing until now. Even though adjuvant treatment is recommended for 'high risk' stage II, the endeavor to answer for question-who should be treated by what-is needed.
Camptothecin ; Chemotherapy, Adjuvant ; Colon ; Colonic Neoplasms ; Colorectal Neoplasms ; Korea ; Organoplatinum Compounds ; Public Health ; Recurrence ; Standard of Care

BACKGROUND/AIMS: No standard chemotherapy has been established for advanced gallbladder cancer. The authors studied the activity and tolerability of a gemcitabine and oxaliplatin (GEMOX) combination in unresectable gallbladder cancer (GBC). METHODS: Adult patients with pathologically confirmed unresectable GBC were prospectively recruited at three centers. No patient had received prior chemotherapy or radiotherapy. Patients received cycles of gemcitabine at 1,000 mg/m2 on day 1, followed by oxaliplatin at 100 mg/m2 on day 2, every 2 weeks. The primary study endpoint was time to progression. RESULTS: Forty patients with unresectable GBC were enrolled. The median age was 60 years (range, 38 to 79 years). All patients showed good performance status. Of the 33 analyzable patients, 12 achieved partial response (36%), 17 stable disease (52%), and four progressive disease (12%). No patient achieved a complete response. The tumor control rate was 88%. At a median follow-up of 6.8 months, the median time to progression was 5.3 months (95% confidence interval [CI], 3.7 to 6.9), and median overall survival was 6.8 months (95% CI, 6.1 to 7.5). Nine of the 40 patients (23%) experienced at least a grade-3 adverse event, but no patient experienced a grade-4 adverse event. CONCLUSIONS: GEMOX combination therapy is a feasible option and is well tolerated in unresectable GBC.
Adult ; Deoxycytidine ; Follow-Up Studies ; Gallbladder ; Gallbladder Neoplasms ; Humans ; Organoplatinum Compounds ; Prospective Studies

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

PURPOSE: The purpose of this study was to evaluate efficacy and toxicity of irinotecan, leucovorin and 5-fluorouracil (FOLFIRI) as second-line treatment after failure of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX) for advanced gastric cancer. MATERIALS AND METHODS: Patients who received modified FOLFOX-4 as first-line treatment and then received sequential modified FOLFIRI for disease progression were included in this study. The modified FOLFIRI regimen consisted of irinotecan 150 mg/m2 in a 90-minute intravenous infusion on day 1, leucovorin (LV) 20 mg/m2 and 5-fluorouracil (5-FU) 400 mg/m2 as a bolus followed by 600 mg/m2 as a 22-hour infusion on days 1 and 2 with the same dose of 5-FU/LV of modified FOLFOX-4 every 2 weeks. RESULTS: A total of 32 patients received 126 courses of FOLFIRI chemotherapy. No complete response was achieved. Three patients (9.4%; 95% confidence interval [CI], 0 to 20.1%) achieved partial response, whereas 11 (34.4%; 95% CI, 17.0 to 51.8%) patients showed stable disease. Disease control rate (complete response, partial responses and stable diseases) was 43.8% (95% CI, 25.6 to 61.9%) and median follow up duration was 11.3 months (range, 2.23 to 37.9 months). Median time to progression was 2 months (95% CI, 1.49 to 2.51 months), and median overall survival from the start of FOLFIRI was 5.84 months (95% CI, 4.34 to 7.34 months). Toxicities were tolerable. CONCLUSION: Modified FOLFIRI as second-line chemotherapy after failure of the modified FOLFOX-4 in advanced gastric cancer was tolerable but showed a lower response rate. Further study about retrying 5-FU/LV with irinotecan after failure of the 5-FU/LV combined regimen is necessary in advanced gastric cancer.
Camptothecin ; Disease Progression ; Fluorouracil ; Follow-Up Studies ; Humans ; Infusions, Intravenous ; Leucovorin ; Organoplatinum Compounds ; Stomach Neoplasms

PURPOSE: The purpose of this study was to evaluate efficacy and toxicity of irinotecan, leucovorin and 5-fluorouracil (FOLFIRI) as second-line treatment after failure of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX) for advanced gastric cancer. MATERIALS AND METHODS: Patients who received modified FOLFOX-4 as first-line treatment and then received sequential modified FOLFIRI for disease progression were included in this study. The modified FOLFIRI regimen consisted of irinotecan 150 mg/m2 in a 90-minute intravenous infusion on day 1, leucovorin (LV) 20 mg/m2 and 5-fluorouracil (5-FU) 400 mg/m2 as a bolus followed by 600 mg/m2 as a 22-hour infusion on days 1 and 2 with the same dose of 5-FU/LV of modified FOLFOX-4 every 2 weeks. RESULTS: A total of 32 patients received 126 courses of FOLFIRI chemotherapy. No complete response was achieved. Three patients (9.4%; 95% confidence interval [CI], 0 to 20.1%) achieved partial response, whereas 11 (34.4%; 95% CI, 17.0 to 51.8%) patients showed stable disease. Disease control rate (complete response, partial responses and stable diseases) was 43.8% (95% CI, 25.6 to 61.9%) and median follow up duration was 11.3 months (range, 2.23 to 37.9 months). Median time to progression was 2 months (95% CI, 1.49 to 2.51 months), and median overall survival from the start of FOLFIRI was 5.84 months (95% CI, 4.34 to 7.34 months). Toxicities were tolerable. CONCLUSION: Modified FOLFIRI as second-line chemotherapy after failure of the modified FOLFOX-4 in advanced gastric cancer was tolerable but showed a lower response rate. Further study about retrying 5-FU/LV with irinotecan after failure of the 5-FU/LV combined regimen is necessary in advanced gastric cancer.
Camptothecin ; Disease Progression ; Fluorouracil ; Follow-Up Studies ; Humans ; Infusions, Intravenous ; Leucovorin ; Organoplatinum Compounds ; Stomach Neoplasms

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

PURPOSE: The platinum-based modified FOLFOX-6 has been reported as an acceptable chemotherapeutic regimen in treatment of advanced gastric cancer patients. The response rate and drug-induced toxicity of platinum-based chemoagents is different according to several gene polymorphism such as ERCC1, XRCC1 and GSTP1 genes, which were related with therapeutic mechanisms. We aimed to evaluate the effect of gene polymorphism and determine the possibility as prediction factor for responsibility in advanced and recurrent gastric cancer patients treated with modified FOLFOX-6 regimen. METHODS: This study was conducted with 55 patients. We sampled 20 ml of peripheral blood to isolate DNA from lymphocytes, and identified genotypes of 3 genes (ERCC1, XRCC1, GSTP1) by PCR-RFL of extracted DNA. Based on medical records, retrospective analysis was made on the patients' clinical characteristics. RESULTS: The overall response rate to modified FOLFOX-6 was 40.0% (22/55). In polymorphism of ERCC1 C8092A, the wild type (CC) showed a statistically significantly lower response rates to chemoagents than the mutant type (CA/AA). In the subtypes of ERCC1 C118T, however, the wild type (CC) showed statistically significantly lower hematological toxicity than the mutant type (CA/AA). But, there was no statistically significance in survival analysis. CONCLUSION: We suggest that ERCC1 gene polymorphism is clinically more adequate as a feasible factor for predicting the response rate and toxicity of modified FOLFOX-6 regimen in gastric cancer patients.
DNA ; Genotype ; Humans ; Lymphocytes ; Medical Records ; Organoplatinum Compounds ; Retrospective Studies ; Stomach Neoplasms

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