No abstract available.
Organoplatinum Compounds

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

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

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

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

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

OBJECTIVETo compare the differences of the efficacy and adverse reaction of Oxaliplatin (L-OHP) treatment to oral squamous cell carcinoma (OSCC) at four different daily time points, and to analyze the characteristics of circadian rhythms.

METHODSSeventy-five nude mice were placed under 12h light and 12h dark cycles. Human OSCC cell line BcaCD885 was inoculated on the cheek of nude mice to establish a nude mice model of OSCC. After 3 weeks, mice were divided into 5 groups (4 experimental groups and 1 control group), with 15 in each group. L-OHP (17 mg x kg(-1)) was injected intravenously at 4 different time points during a period of 24 h, including 4 hours after lights on JHALO), 10 HALO, 16 HALO and 22 HALO for 4 experimental groups. The control group received normal saline of the same volume as that of L-OHP. The efficacy (tumor inhibition rate and survival time) and adverse reaction (body weight, white blood cell and perianal swelling) were observed after administration. The circadian rhythms of the efficacy and adverse reaction were examined by cosine analysis.

RESULTSL-OHP injected at 4, 16 and 22 HALO had great tumor inhibition rates, however, only 16 and 22 HALO groups significantly prolonged survival time of mice. The adverse reactions at 4 and 10 HALO were significantly severer than that of 16 and 22 HALO. Cosine analysis showed survival time, body weight and white blood cell counts had significant circadian rhythms. Mice received L-OHP at 14.88 HALO had the longest survival time.

CONCLUSIONThe time factor should be considered in L-OHP chronchemotherapy of patients with OSCC in order to increase the efficacy, decrease the adverse reaction of the drug and to improve the life quality of patients with OSCC.

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

Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Humans ; Organoplatinum Compounds ; chemical synthesis

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