• Journal of Korean Academy of Nursing
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• v.45 no.6
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• pp.783-801
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• 2015

Purpose: The purpose of this study is to provide a comprehensive overview of the various measures available for assessment of oxaliplatin-induced peripheral neuropathy (OXLIPN) and to evaluate the measurement properties of each assessment tool. Methods: A systematic review was conducted to identify existing measures for OXLIPN found in the databases of PubMed, Cochrane Library, Embase, RISS and KoreaMed. The quality of the 24 identified tools was evaluated based on their properties of measurement including content validity, internal consistency, criterion validity, construct validity, reproducibility, responsiveness, floor-ceiling effects and interpretability. Results: Ten (41.7%) of the 24 tools were identified as specific measures for assessing OXLIPN and the most popular type of measures were clinical grading systems by clinicians (58.3%) and only 29.2% of measures were identified as patient reported outcomes. The most frequently used tool was National Cancer Institute-Common Toxicity Criteria (NCI-CTC), but the validity of NCI-CTC has not been reported appropriately. Overall, the Neuropathic Pain Symptom Inventory (NPSI) received the best psychometric scores, and the Chemotherapy-induced Peripheral Neuropathy Assessment Tool (CIPNAT) and Functional Assessment of Cancer Therapy/Gynaecologic Oncology Group-neurotoxicity-12 (FACT/GOG-Ntx-12) followed NPSI. Conclusion: To select appropriate measure, evidences should be accumulated through the clinical use of tools. Therefore, practitioner and researchers are urged to report relevant statistics required for the validation of the currently used measures for assessment of OXLIPN.

• Journal of Gastric Cancer
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• v.17 no.1
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• pp.21-32
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• 2017

Purpose: Perioperative chemotherapy improves survival outcomes in locally advanced (LA) gastric cancer. Materials and Methods: We retrospectively analyzed patients with LA gastric cancer who were offered perioperative chemotherapy consisting of epirubicin, oxaliplatin, and capecitabine (EOX) from May 2013 to December 2015 at Tata Memorial Hospital in Mumbai. Results: Among the 268 consecutive patients in our study, 260 patients (97.0%) completed neoadjuvant chemotherapy, 200 patients (74.6%) underwent D2 lymphadenectomy, and 178 patients (66.4%) completed adjuvant chemotherapy. The median follow-up period was 17 months. For the entire cohort, the median overall survival (OS), 3-year OS rate, median progression-free survival (PFS), and 3-year PFS rate were 37 months, 64.4%, 31 months, and 40%, respectively. PFS and OS were significantly inferior in patients who presented with features of obstruction than in those who did not (P=0.0001). There was no difference in survival with respect to tumor histology (well to moderately differentiated vs. poorly differentiated, signet ring vs. non-signet ring histology) or location (proximal vs. distal). Survival was prolonged in patients with an early pathological T stage and a pathological node-negative status. In a multivariate analysis, postoperative pathological nodal status and gastric outlet obstruction on presentation significantly correlated with survival. Conclusions: EOX chemotherapy with curative resection and D2 lymphadenectomy is a suggested alternative to the existing perioperative regimens. The acceptable postoperative complication rate and relatively high resections, chemotherapy completion, and survival rates obtained in this study require further evaluation and validation in a clinical trial.

• Asian Oncology Nursing
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• v.12 no.4
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• pp.305-313
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• 2012

Purpose: This study was done to clarify the effects of foot reflexology on peripheral neuropathy, symptom distress, anxiety and depression in cancer patients treated with oxaliplatin. Methods: A quasi-experimental design was employed. Changes in the variables were evaluated to test the effects of foot reflexology. Participants were cancer patients treated with oxaliplatin (experimental group 14 and control group 17). Peripheral neuropathy, symptom distress, anxiety and depression were measured before and after reflexology. Data were collected from October, 2010 to April, 2011. ${\chi}^2$-test, Fisher's exact test, t-test, Wilcoxon signed rank test and the Mann-Whitney U test were used to analyze the data. Results: The experimental group who received foot reflexology experienced less peripheral neuropathy and symptom distress than the control group. There was no difference in anxiety and depression between the experimental and control group. Conclusion: The foot reflexology program adopted in this study was found to be an effective method to reduce peripheral neuropathy and symptom distress. We recommend foot reflexology for patients with chemotherapy induced peripheral neuropathy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4515-4520
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• 2015

GELOX (gemcitabine, oxaliplatin and L-asparaginase) regimen showed an impressive result in our previous study, but the effect of this new regimen is still dissatisfying for some patients, so it is necessary to identify which patients will benefit from this regimen. A total of fifty-one cases with nasal natural killer/T-cell lymphoma receiving initial GELOX chemotherapy were enrolled in this study. The ki-67 expression detected by immunohistochemistry (IHC) in the specimens ranged from 10% to 90%, with a median value of 70%, so cases higher than the median value (${\geq}70%$) were defined as high ki-67 expression, and the others were designated as low ki-67 expression. The response rate had no statistical difference between low ki-67 expression group and high ki-67 expression group (P=0.291) though the value in the former group was relatively high. After a median follow-up of 18.03 months, the 3-year progression-free survival (PFS) for patients with low ki-67 expression was significantly higher than those with high ki-67 expression (83.8% vs. 47.9%, P=0.038). In the stage I/II subgroup, 3-year PFS and overall survival (OS) were statistically higher in the patients with low ki-67 expression than those with high ki-67 expression. Multivariate analysis revealed high ki-67 expression was an independent prognostic factor for PFS. These results suggest that low ki-67 expression can predict a good response of GELOX in these patients, and the combination of ki-67 expression and early stage is helpful to identify an excellent prognosis subgroup from patients receiving GELOX in this disease.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3465-3469
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• 2012

Aim: Platinum agents have shown to be effective in the treatment of colorectal cancer. We assessed whether single nucleotide polymorphisms (SNPs) in GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln might predict the overall survival in patients receiving oxaliplatin-based chemotherapy in a Chinese population. Methods: SNPs of GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln in 335 colorectal cancer patients were assessed using TaqMan nuclease assays. Results: At the time of final analysis on Nov. 2011, the median follow-up period was 37.7 months (range from 1 to 60 months). A total of 229 patients died during follow-up. Our study showed GSTP1 Val/Val (HR=0.44, 95% CI=0.18-0.98), ERCC1 C/C (HR=0.20, 95% CI=0.10-0.79) and ERCC2 G/G (HR=0.48, 95% CI=0.19-0.97) to be significantly associated with better survival of colorectal cancer. GSTP1 Val/Val, ERCC1 C/C and ERCC2 G/G were also related to longer survival among patients with colon cancer, with HRs (95% CIs) of 0.41 (0.16-0.91), 0.16 (0.09-0.74) and 0.34 (0.16-0.91), respectively. Conclusion: GSTP1, GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln genotyping might facilitate tailored oxaliplatin-based chemotherapy for colorectal cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3085-3091
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• 2013

Associations between ABCB1 and XPC genetic polymorphisms and risk of developing colorectal cancer (CRC) as well as clinical outcomes in CRCs with chemotherapy were investigated. A case-control study was performed on the ABCB1 C3435T, G2677T/A and XPC Lys939Gln polymorphisms in 428 CRC cases and 450 hospitalbased, age and sex frequency-matched controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays. We observed that the ABCB1 3435CT or CC+CT variants were significantly linked with increasing risk of developing CRC (adjusted OR (95% CI): 1.814 (1.237-2.660), P=0.0022; adjusted OR (95% CI): 1.605 (1.117-2.306), P=0.0102, respectively). Moreover, the distribution frequency of XPC AC genotype or AC+CC genotypes also showed a tendency towards increasing the suscepbility for CRC (P=0.0759 and P=0.0903, respectively). Kaplan-Meier curves showed that the ABCB1 C3435T variant was associated with a tendency toward longer progression-free survival (PFS) (n=343, Log-rank test: P=0.063), and the G2677T/A variant genotypes (GT+TT+GA+AA) with a tendency for longer OS in postoperative oxaliplatin-based patients (n=343, Log-rank test: P=0.082). However, no correlation of the XPC Lys939Gln polymorphism was found with PFS and OS in patients with postoperative oxaliplatin-based chemotherapy (n=343). Our study indicated that ABCB1 polymorphisms might be candidate pharmacogenomic factors for the prediction of CRC susceptibility, but not for prognosis with oxaliplatin chemosensitivity in CRC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3277-3280
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• 2016

Background: Gastric cancer is considered the fourth most common cancer and second most common cause of cancer-related mortalities worldwide. Gastric cancer develops more frequently among elderly. The oxaliplatin/5FU/leucovorin (FOLFOX) regimen has shown a notable activity against gastric cancer. Aim: To evaluate the responses and complications of FOLFOX-4 regimen as first line chemotherapy in elderly patients with advanced gastric cancer. Materials and Methods: From October 2014 to November 2015, a total of 21 patients with metastatic or local AGC (advanced gastric cancer) were analyzed. All patients were administered a FOLFOX-4 regimen consisting of a 2h infusion of oxaliplatin $85mg/m^2$ (day 1), continuous infusion of $1000mg/m^2$ 5-Fu in 24h., and leucovorin $200mg/m^2$ in 2h infusion as a first-line chemotherapy. Results: A total of 18 patients were assessable for efficacy and toxicity. One of 18 patients achieved a complete response, and 12 had partial responses, giving an overall response rate of 72.6%. Three (16%) patients demonstrated stable disease and 2 (12%) progression. The median progression free survival was 7.3 months, and the median overall survival was 11.9 months. One patient had grade 3 neuropathy. No other grade 3 or 4 NCI-CTC were seen. Conclusions: The FOLFOX-4 regimen used in our study was both active and acceptable for AGC in elderly patients as neoadjuvant and main therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5941-5944
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• 2014

Purpose: To highlight the potential factors that could predict the response rate of patients with metastatic colorectal cancer (mCRC) treated with pemetrexed combined chemotherapy after first- or second-line chemotherapy using the FOLFOX regimen. Materials and Methods: Between January 2007 and July 2014, 54 patients diagnosed and pathologically-confirmed with advanced colorectal cancer in Jiangsu Cancer Hospital and Research Institute, were enrolled. They received pemetrexed at a dose of $500mg/m^2$ by 10 minute infusion on day 1, repeated every 3 weeks. Doses were modified depending on nadir counts of blood cells. Combined chemotherapeutic agents included irinotecan, lobaplatin, carboplatin, oxaliplatin, gemcitabine, cis-platinum or bevacizumab. Multiple variables (age, sex, hemoglobin, platinum drugs combined, metastasis sites, LDH, ALP, CEA>40 ug/ml) reported earlier were selected. We used logistic regression analysis to evaluate relationships between these and tumor response. Results: On multivariable analysis, we found that age was significant in predicting the responsiveness to pemetrexed (p<0.05) combined with oxaliplatin. We did not find any other factors which were significantly associated with the response rate to chemotherapy with pemetrexed and irinotecan. Conclusions: By multivariate analysis, we found that age had significant impact on the responsiveness of pemetrexed when combined with oxaliplatin. Additional research based on genomic properties of host and tumors are needed to clarify markers for better selection of patients who could benefit from pemetrexed combined chemotherapy.

• Journal of Gastric Cancer
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• v.21 no.4
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• pp.418-425
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• 2021

Purpose: We designed a new regimen by combining intraperitoneal (IP) paclitaxel (PTX) with systemic S-1 plus oxaliplatin (SOX) for the treatment of advanced gastric cancer with peritoneal metastasis. This dose-escalation study aimed to determine the maximum tolerated dose (MTD) and recommended dose (RD) of IP PTX administered weekly to patients. Materials and Methods: Eight cycles of IP PTX plus SOX regimen were administered to the patients. S-1 was administered orally twice daily at a dose of 80 mg/m²/day for 14 consecutive days, followed by 7 days of rest. Intravenous oxaliplatin was administered at a fixed dose of 100 mg/m² on day 1, while IP PTX was administered on days 1 and 8. The initial dose of IP PTX was 40 mg/m², and the dose escalation was set in units of 20 mg/m² up to 80 mg/m². Dose-limiting toxicities (DLTs) were defined as grade 3 non-hematologic toxicities, grade 4 leukopenia, grade 3 febrile neutropenia, and grade 3 thrombocytopenia. Results: Nine patients were included in the study. No DLTs were observed in any of the enrolled patients. Therefore, the MTD was not reached, and the RD of IP PTX was determined to be 80 mg/m². Four patients (44%) showed a decreased peritoneal cancer index score on second-look laparoscopic examination. Conclusions: The present study determined the dose for further clinical trials of IP PTX to be 80 mg/m², when combined with a systemic SOX regimen.

• Biomolecules & Therapeutics
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• v.31 no.6
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• pp.661-673
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• 2023

Treatment of colorectal cancer (CRC) has always been challenged by the development of resistance. We investigated the antiproliferative activity of licochalcone H (LCH), a regioisomer of licochalcone C derived from the root of Glycyrrhiza inflata, in oxaliplatin (Ox)-sensitive and -resistant CRC cells. LCH significantly inhibited cell viability and colony growth in both Ox-sensitive and Ox-resistant CRC cells. We found that LCH decreased epidermal growth factor receptor (EGFR) and AKT kinase activities and related activating signaling proteins including pEGFR and pAKT. A computational docking model indicated that LCH may interact with EGFR, AKT1, and AKT2 at the ATP-binding sites. LCH induced ROS generation and increased the expression of the ER stress markers. LCH treatment of CRC cells induced depolarization of MMP. Multi-caspase activity was induced by LCH treatment and confirmed by Z-VAD-FMK treatment. LCH increased the number of sub-G1 cells and arrested the cell cycle at the G1 phase. Taken together LCH inhibits the growth of Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, and inducing ROS generation and ER stress-mediated apoptosis. Therefore, LCH could be a potential therapeutic agent for improving not only Ox-sensitive but also Ox-resistant CRC treatment.