• 한국임상약학회지
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• 제19권1호
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• pp.18-22
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• 2009

Oxaliplatin is a tolerable and effective drug of choice in the treatment of advanced or metastatic gastric cancer. However, it has many dose-limiting neurotoxicities. This study was performed to assess the incidence and types of oxaliplatin-related neurotoxicities. Sixty-four patients receiving oxaliplatin-involved regimen as salvage therapy on metastatic gastric cancer or as the first-line therapy on advanced gastric cancer were evaluated during the period between September 1, 2006 and February 29, 2008. The patients were treated with oxaliplatin 100 $mg/m^2$ and leucovorin 100 $mg/m^2$ simultaneously as 2-hour-lasting infusion on Day-1 followed by 5-FU 1200 $mg/m^2$ as a 22-hour-lasting continuous infusion both on Day-1 and Day-2 by every other week. We developed questionnaires to evaluate patient-recognized neurotoxic symptoms rather than the observer-described events. Surveys were completed at bedside or via telephone interview. Acute and chronic neurotoxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC, version 3) as well as the Oxaliplatin-specific Neurotoxicity Scale. The Grade-3 neuropathy was reported in 19% of the patients (n=12) and grade-1/2 neuropathy occurred in 70% (n=45). The most common symptom was cold-related dysesthesia (83%) regarded as nociperception by the patients. Some patients (19%) experienced functional impairment affecting activities of daily living such as writing, buttoning, and walking. Even though 74% of the patients (42/57) were prescribed with gabapentin to reduce these peripheral symptoms, it did not appear to derive any benefit from this medication. It is suggested that notify the patients about their oxaliplatin-associated, debilitating symptoms, and educate them any self-care strategy at the initiating phase of the chemotherapy. Moreover, it needs to design the intervention studies regarding the prevention and management of the peripheral neuropathy.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7603-7606
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• 2015

Background: The chemotherapeutic agent oxaliplatin can cause acute and chronic forms of peripheral neuropathy. The aim of this study was to evaluate the incidence of chronic neuropathy and its risk factors in colorectal cancer (CRC) patients treated with FOLFOX or XELOX regimens in the Oncology Ward of Hazrate-Rasoul Hospital in Tehran. Materials and Methods: A total of 130 patients with CRC were entered into our study, aged over 18 years, without history of receiving other neurotoxic agents or other predisposing factors such as diabetes or neurologic diseases and kidney and liver dysfunction. For the FOLFOX regimen, patients received oxaliplatin, 85mg/m2, every 2 weeks for 12 courses and with the XELOX regimen, oxaliplatin was $130mg/m^2$, every 3 weeks for 8 courses. Based on Common Toxicity Criteria (CTC or NCI-CTC v.3), the patients were divided into 5 groups (grades) based on the severity of their symptoms. Results: Fifty-seven patients (43.8%) were male and 73(56.2%) female. Some 19 patients (14.7%) had BMI<20, 97(74.6%) were between 20-25 and 14 (10.8%) ${\geq}25$. In 105 patients (80.7%) neuropathy was found. There was significant correlation between BMI, hypomagnesaemia and especially, severity of anemia in patients with neuropathy compared to those without. Conclusions: Oxaliplatin regimens can induce chronic neuropathy in CRC patients, with anemia, high BMI and hypomagnesaemia as risk factors that can predispose to this kind of neurotoxicity.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8383-8390
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• 2014

Background: Although the predictive value of the excision repair cross-complementing group 1 (ERCC1) C118T polymorphism in clinical outcomes of patients with colorectal cancer (CRC) receiving oxaliplatin-based chemotherapy has been evaluated in numerous published studies, the conclusions are conflicting. Therefore, we performed the present meta-analysis to determine the precise role of the ERCC1 C118T polymorphism in this clinical situation and help optimize individual chemotherapy. Materials and Methods: A multiple search strategy was used to identify eligible studies. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were used to estimate objective response and oxaliplatin-induced toxicity, with hazard ratios (HRs) with 95%CIs for progression-free survival (PFS) and overall survival (OS). Results: A total of 22 studies including 2,846 CRC patients were eligible in the analysis. Overall, no significant correlation was found between the ERCC1 C118T polymorphism and objective response to oxaliplatin-based chemotherapy, in all patients or in the Asian and Caucasian subgroups. However, the pooled analysis showed that the PFS and OS were significantly shorter in patients who carried T/T or T/C genotypes of ERCC1 C118T as compared to the C/C genotype. On stratified analysis by ethnicity, the ERCC1 118T allele was associated with a favorable prognosis in Caucasians (PFS, HR=0.58, 95%CI: 0.24-1.44; OS, HR=0.38, 95%CI: 0.22-0.64) but an unfavorable prognosis in Asians (PFS, HR=2.49, 95%CI: 1.87-3.33; OS, HR=2.63, 95%CI: 1.87-3.69) based on a dominant model. In addition, we failed to find a statistically significant impact of ERCC1 C118T polymorphism on oxaliplatin-induced toxicity. Conclusions: The ERCC1 C118T polymorphism may have prognostic value in patients with CRC undergoing oxaliplatin-based chemotherapy.

• Biomolecules & Therapeutics
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• 제26권6호
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• pp.591-598
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• 2018

Epigenetic silencing is considered to be a major mechanism for loss of activity in tumor suppressors. Reversal of epigenetic silencing by using inhibitors of DNA methyltransferase (DNMT) or histone deacetylases (HDACs) such as 5-Aza-CdR and FK228 has shown to enhance cytotoxic activities of several anticancer agents. This study aims to assess the combinatorial effects of genesilencing reversal agents (5-Aza-CdR and FK228) and oxaliplatin in gastric cancer cells, i.e., Epstein-Barr virus (EBV)-negative SNU-638 and EBV-positive SNU-719 cells. The doublet combinatorial treatment of 5-Aza-CdR and FK228 exhibited synergistic effects in both cell lines, and this was further corroborated by Zta expression induction in SNU-719 cells. Three drug combinations as 5-Aza-CdR/FK228 followed by oxaliplatin, however, resulted in antagonistic effects in both cell lines. Simultaneous treatment with FK228 and oxaliplatin induced synergistic and additive effects in SNU-638 and SNU-719 cells, respectively. Three drug combinations as 5-Aza-CdR prior to FK228/oxaliplatin, however, again resulted in antagonistic effects in both cell lines. This work demonstrated that efficacy of doublet synergistic combination using DNMT or HDACs inhibitors can be compromised by adding the third drug in pre- or post-treatment approach in gastric cancer cells. This implies that the development of clinical trial protocols for triplet combinations using gene-silencing reversal agents should be carefully evaluated in light of their potential antagonistic effects.

• Journal of Gastric Cancer
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• 제13권2호
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• pp.121-125
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• 2013

Gastric cancer patients with acute disseminated intravascular coagulation experiences a rare but severe complication resulting in a dismal prognosis. We report a case of advanced gastric cancer complicated with disseminated intravascular coagulation with intractable tumor bleeding which was successfully treated with chemotherapy consisting of 5-fluorouracil and oxaliplatin. The patient was a 63-yearold man who complained of abdominal pain, melena, and dyspnea on 24 November 2010. We diagnosed stage IV gastric cancer complicated by disseminated intravascular coagulation. Gastric tumor bleeding was not controlled after procedures were repeated three times using gastrofiberscopy. With the patient's consent, we selected the 5-fluorouracil and oxaliplatin combination chemotherapy for treatment. After one cycle of 5-fluorouracil and oxaliplatin therapy, symptoms of bleeding improved and the disseminated intravascular coagulation process was successfully controlled. The primary tumor and multiple metastatic bone lesions were remarkably shrunken and metabolically remitted after eight cycles of chemotherapy. In spite of progression, systemic chemotherapy is effective in disease control; further, the patient gained the longest survival time among cases of gastric cancer with disseminated intravascular coagulation.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.1845-1849
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• 2012

Objective: Tissue factor (TF) is expressed abnormally in certain types of tumor cells, closely related to invasion and metastasis. The aim of this study was to construct a human gastric cancer cell line SGC7901 stably-transfected with human TF, and observe effects on oxaliplatin-dependent inhibition of invasion and the apoptosis induction. Methods: The target gene TF was obtained from human placenta by nested PCR and introduced into the human gastric cell line SGC7901 through transfection mediated by lipofectamine. Stably-transfected cells were screened using G418. Examples successfully transfected with TF-pcDNA3 recombinant (experimental group), and empty vector pcDNA3 (control group) were incubated with oxaliplatin. Transwell chambers were used to show change in invasive ability. Caspase-3 activity was detected using a colorimetric method and annexin-V/PI double-staining was applied to detect apoptosis. Results: We generated the human gastric cancer cell line SGC7901/TF successfully, expressing TF stably and efficiently. Compared with the control group, invasion increased, whereas caspase-3 activity and apoptosis rate were decreased in the experimental group. Conclusion: TF can enhance the invasive capacity of gastric cancer cells in vitro. Its increased expression may reduce invasion inhibition and apoptosis-inducing effects of oxaliplatin and therefore may warrant targeting for improved chemotherapy.

• The Korean Journal of Physiology and Pharmacology
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• 제20권4호
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• pp.407-414
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• 2016

This study was performed to investigate whether the spinal cholinergic and serotonergic analgesic systems mediate the relieving effect of electroacupuncture (EA) on oxaliplatin-induced neuropathic cold allodynia in rats. The cold allodynia induced by an oxaliplatin injection (6 mg/kg, i.p.) was evaluated by immersing the rat's tail into cold water ($4^{\circ}C$) and measuring the withdrawal latency. EA stimulation (2 Hz, 0.3-ms pulse duration, 0.2~0.3 mA) at the acupoint ST36, GV3, or LI11 all showed a significant anti-allodynic effect, which was stronger at ST36. The analgesic effect of EA at ST36 was blocked by intraperitoneal injection of muscarinic acetylcholine receptor antagonist (atropine, 1 mg/kg), but not by nicotinic (mecamylamine, 2 mg/kg) receptor antagonist. Furthermore, intrathecal administration of $M_2$ (methoctramine, $10{\mu}g$) and $M_3$ (4-DAMP, $10{\mu}g$) receptor antagonist, but not $M_1$ (pirenzepine, $10{\mu}g$) receptor antagonist, blocked the effect. Also, spinal administration of $5-HT_3$ (MDL-72222, $12{\mu}g$) receptor antagonist, but not $5-HT_{1A}$ (NAN-190, $15{\mu}g$) or $5-HT_{2A}$ (ketanserin, $30{\mu}g$) receptor antagonist, prevented the anti-allodynic effect of EA. These results suggest that EA may have a significant analgesic action against oxaliplatin-induced neuropathic pain, which is mediated by spinal cholinergic ($M_2$, $M_3$) and serotonergic ($5-HT_3$) receptors.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9699-9706
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• 2014

Background: The predictive value of the xeroderma pigmentosum group D (XPD) Lys751Gln polymorphism regarding clinical outcomes of patients with colorectal cancer (CRC) receiving oxaliplatin-based chemotherapy has been evaluated in numerous published studies, but the results remain inconclusive. Therefore, we performed a meta-analysis to determine the precise role of the XPD Lys751Gln polymorphism in this clinical situation and optimize individual chemotherapy. Materials and Methods: A multiple search strategy was used to identify eligible studies. Pooled odds ratios (ORs), generalized odds ratio (ORG) and their 95% confidence intervals (CIs) were used to estimate the objective response, while hazard ratios (HRs) with 95%CIs were used for progression-free survival (PFS) and overall survival (OS). Results: A total of 17 studies including 2,286 patients met the inclusion criteria. Overall, the XPD 751Gln allele was associated with a non-significant reduced objective response to oxaliplatin-based chemotherapy in all patients or in the Asian and Caucasian subgroups. However, poor PFS and OS of CRC patients treated with oxaliplatin-based regimens were significantly related to the XPD 751Gln allele in the dominant model (PFS: HR=2.10, 95%CI: 1.65-2.67; OS: HR=3.18, 95%CI: 1.57-6.47). On stratified analysis by ethnicity, these relationships were more pronounced in Asians (PFS: HR=2.49, 95%CI: 1.79-3.47; OS: HR=5.25, 95%CI: 3.46-7.94) than in Caucasians (PFS: HR=1.73, 95%CI: 1.22-2.46; OS: HR=1.78, 95%CI: 1.06-2.99). Conclusions: The XPD Lys751Gln polymorphism may have prognostic value in patients with CRC undergoing oxaliplatin-based chemotherapy.

• Tuberculosis and Respiratory Diseases
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• 제59권5호
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• pp.536-540
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• 2005

저자들은 64세 남자 환자에서, 재발성 위암에 대한 oxaliplatin, 5-fluorouracil, leucovorin 병합화학요법 중에 발생한 폐섬유화증의 임상적 진단 및 스테로이등 충격 요법 치료 후 호전된 증례를 경험하였기에 문헌 고찰과 함께 보고하는 바이다.

• Bulletin of the Korean Chemical Society
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• 제31권7호
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• pp.2043-2046
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• 2010