• Title, Summary, Keyword: oxaliplatin

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Oxaliplatin Induced Angioedema in a Rectal Cancer Patient: A Clinical Case Report (직장암 환자에서 Oxaliplatin 투여로 인한 혈관부종 발생 증례 보고)

  • Noh, Mi-Hee;Lee, Yu-Jeung
    • Korean Journal of Clinical Pharmacy
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    • v.21 no.4
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    • pp.390-393
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    • 2011
  • We report an unusual case of angioedema induced by intravenous oxaliplatin in a patient with rectal cancer. Intravenous oxaliplatin was administered to the patient according to FOLFOX regimen (oxaliplatin/leucovorin/5-fluorouracil) for the management of his colorectal carcinoma. The patient had been on FOLFOX regimen for several months without reporting any adverse effects, but he experienced angioedema suddenly during his $9^{th}$ cycle of chemotherapy. Angioedema was observed about 2 hours after the initiation of oxaliplatin infusion. Oxaliplatin was stopped then the patient became stable. This case report demonstrates that intravenous oxaliplatin may induce angioedema several hours after the initiation of oxaliplatin infusion in later cycles of chemotherapy.

Dose Intensity of Oxaliplatin in 5-Fluorouracil and Leucovorin Regimens in Pretreated Metastatic Colorectal Cancer (5-Fluorouracil, Leucovorin과 병용 투여된 Oxaliplatin의 Dose Intensity가 재발된 전이성 대장암 치료에 미치는 영향)

  • Jeong, Kyong-Ju;Choi, Seung-Ki;Oh, Jung-Mi
    • Korean Journal of Clinical Pharmacy
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    • v.14 no.1
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    • pp.1-10
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    • 2004
  • Studies of oxaliplatin, 5-fluorouracil and leucovorin in pretreated metastatic colorectal cancer showed that oxaliplatin dose intensity is important prognostic factor for objective response rates and progression-free-survival (PFS). To evaluate response rates, PFS and toxicity according to oxaliplatin dose intensity, we retrospectively analyzed data from patients with metastatic colorectal cancer received oxaliplatin,5-fluorouracil, leucovorin regimens. Sixty-three patients were reviewed in this study, 42 patients received low dose intensity oxaliplatin (LDI: $\leq85\;mg/m^2/2wks$) and 21 patients high dose intensity oxaliplatin (HDI: $>85\;mg/m^2/2wks$). Objective responses occurred in 10 $(47.7\%)$ HDI patients and 9 $(21.4\%)$ LDI patients (p = 0.014). Median PFS was 24.7 weeks in HDI group, with $45.1\%$ of HDI patients progression free at 6 months, and 20.5 weeks in LDI group, with $33.5\%$ of LDI patients progression free at 6 months (p = 0.344). Increased oxaliplatin dose intensity was not associated with neutropenia, thrombocytopenia, neuropathy, nausea and vomiting. This study showed that oxaliplatin dose intensification significantly improves objective response rate in pretreated metastatic colorectal cancer without increasing severe toxicity.

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Effects of Analgecine on Oxaliplatin-Induced Neurotoxicity in Patients with Gastrointestinal Cancer

  • Liu, Meng-Yan;Huang, Xin-En
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.10
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    • pp.4465-4468
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    • 2015
  • Background: As the third generation of platinum-based antineoplastic agent aginst gastrointestinal cancer, oxaliplatin is considered to be associated with severe sensory neurotoxicity. Acorrding to previous studies, vitaminE, intravenous Ca/Mg and glutamine may partly reduce the incidence and severity of oxaliplatin-induced neurotoxicity. The aim of this study was to investigate the safety and efficacy of analgecine for preventing oxaliplatin-induced neurotoxicity in the patients with gastrointestinal tumors. Method: In this study, patients undergoing oxaliplatin-based chemotherapy were assigned to analgecine (experimental) group or control group. Analgecine 6ml was administered once a day for seven days from the day of oxaliplatin treatment. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; version 3) was used to evaluate oxaliplatin-induced neurotoxicity. The incidence rates and grade of neurotoxicity of patients were assessed before and during (after four and eight cycles) treatment. Results: Totally, 82 patients were enrolled in this study, 42 in experimental group and 40 in control group. The occurrence of each grade neurotoxicity in the experimental group was significantly lower than that in control group. The overall occurrence rate was 31% vs 55% (P=0.043) after 4 cycles and 52% vs 75% (P=0.050) after 8 cycles. Conclusion: Analgecine appears could be effective in reducing oxaliplatin-induced neurotoxicity and be applicated for patients with gastrointestinal tumors who would be treated with oxaliplatin-based chemotherapy.

Clinical Features of Oxaliplatin Induced Hypersensitivity Reactions and Therapeutic Approaches

  • Bano, Nusrat;Najam, Rahila;Qazi, Faaiza;Mateen, Ahmed
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.4
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    • pp.1637-1641
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    • 2016
  • Oxaliplatin, a third generation novel platinum compound is the most effective first line chemotherapeutic agent for colorectal cancer (CRC) in combination with 5FU and leucovorin. It is indicated for pancreatic, gastric and testicular cancers combined with bevacuzimab, capecitabine, irinotecan and other cytotoxic agents. However, moderate to severe hypersensitivity reactions (HSR) during or after oxaliplatin infusion usually require cessation of chemotherapy or substitution of the key therapeutic drug which largely interferes with improved patient prognosis. This mini- review showcases recent and accepted opinions/approaches in oxaliplatin induced HSR management. Physicians and oncologists have varying attitudes regarding the decision to rechallenge the patient after an HSR experience, efficacy of desensitization protocols, effectiveness and selection of drugs for premedication and possibilities of cross sensitivity to other platinum agents (e.g. carboplatin). A brief insight into underlying molecular mechanisms and clinical manifestations of oxaliplatin induced HSR is offered. We have also discussed the management of oxaliplatin induced HSR and risk stratification for a successful and complete chemotherapeutic plan.

Luteolin Sensitizes Two Oxaliplatin-Resistant Colorectal Cancer Cell Lines to Chemotherapeutic Drugs Via Inhibition of the Nrf2 Pathway

  • Chian, Song;Li, Yin-Yan;Wang, Xiu-Jun;Tang, Xiu-Wen
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.6
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    • pp.2911-2916
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    • 2014
  • Oxaliplatin is a first-line therapy for colorectal cancer, but cancer cell resistance to the drug compromises its efficacy. To explore mechanisms of drug resistance, we treated colorectal cancer cells (HCT116 and SW620) long-term with oxaliplatin and established stable oxaliplatin-resistant lines (HCT116-OX and SW620-OX). Compared with parental cell lines, $IC_{50}$s for various chemotherapeutic agents (oxaliplatin, cisplatin and doxorubicin) were increased in oxaliplatin-resistant cell lines and this was accompanied by activation of nuclear factor erythroid-2 p45-related factor 2 (Nrf2) and NADPH quinone oxidoreductase 1 (NQO1). Furthermore, luteolin inhibited the Nrf2 pathway in oxaliplatin-resistant cell lines in a dose-dependent manner. Luteolin also inhibited Nrf2 target gene [NQO1, heme oxygenase-1 (HO-1) and $GST{\alpha}1/2$] expression and decreased reduced glutathione in wild type mouse small intestinal cells. There was no apparent effect in Nrf2-/- mice. Luteolin combined with other chemotherapeutics had greater anti-cancer activity in resistant cell lines (combined index values below 1), indicating a synergistic effect. Therefore, adaptive activation of Nrf2 may contribute to the development of acquired drug-resistance and luteolin could restore sensitivity of oxaliplatin-resistant cell lines to chemotherapeutic drugs. Inhibition of the Nrf2 pathway may be the mechanism for this restored therapeutic response.

Oxaliplatin Sensitizes OS Cells to TRAIL-induced Apoptosis Via Down-regulation of Mcl1

  • Huang, Tao;Gong, Wei-Hua;Li, Xiu-Cheng;Zou, Chun-Ping;Jiang, Guang-Jian;Li, Xu-Hui;Qian, Hao
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.7
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    • pp.3477-3481
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    • 2012
  • Purpose: To investigate the killing effect on OS cells of a combination of oxaliplatin and TRAIL and related molecular mechanisms. Methods: TRAIL and oxaliplatin were applied to OS732 cells singly or jointly and survival inhibition rates were measured by MTT assay, changes of cellular shape being assessed with inverted phase contrast and fluorescence microscopy. Apoptotic rates were analyzed by flow cytometry (FCM) and immunocytochemistry was used to examine Mcl1 expression of OS732 cells. Results: The survival inhibition rate of combined application of $100{\mu}g/ml$ TRAIL and $1{\mu}g/ml$ oxaliplatin on OS-732 cells was significantly higher than that of either agent singly (p<0.01). Changes of cellular shape and apoptotic rates also indicated apoptosis-inducing effects of combined application to be much stronger than those of individual application. Oxaliplatin had the effect of down-regulating Mcl1 expression and sensitizing OS cells to TRAIL-induced apoptosis. Conclusion: A combination of TRAIL and oxaliplatin exerts strong killing effects on OS-732 cells which might be related to down-regulation of Mcl1 expression.

Hypersensitivity Reactions to Oxaliplatin: Clinical Features and Risk Factors in Koreans

  • Kim, Mi-Yeong;Kang, Sung-Yoon;Lee, Suh-Young;Yang, Min-Suk;Kim, Min-Hye;Song, Woo-Jung;Kim, Sae-Hoon;Kim, Yo-Jung;Lee, Keun-Wook;Cho, Sang-Heon;Min, Kyung-Up;Lee, Jong-Seok;Kim, Jee-Hyun;Chang, Yoon-Seok
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1209-1215
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    • 2012
  • Background and Aim: Oxaliplatin hypersensitivity is a well-known adverse reaction but the prevalence varies and data for frequency and clinical features have not been reported for Korea. Here we evaluates the prevalence and risk factors for hypersensitivity reactions to oxaliplatin after chemotherapy. Methods: Clinical information on all patients treated with oxaliplatin was retrospectively reviewed in electronic medical records between August 2009 and July 2010 in Seoul National University Bundang Hospital. Patients who experienced hypersensitivity reactions to oxaliplatin were compared with those who did not. Results: A total of 393 patients received oxaliplatin, with 42 (10.7%) experiencing hypersensitivity reactions including three cases of anaphylaxis. Median cycle of the first hypersensitivity reaction was 8. Reactions correlated with lower dexamethasone doses. Other variables were not significant. Conclusions: The prevalence of hypersensitivity reactions was 10.7%, symptoms being mostly mild and cutaneous. Lower dexamethasone doses could be a predictor for hypersensitivity reactions to oxaliplatin.

Oxaliplatin-induced Peripheral Neuropathy in Patients with Advanced or Metastatic Gastric Cancer (진행성 또는 전이성 위암 환자에 있어서 Oxaliplatin 투여로 인한 말초신경통증 분석)

  • Park, Ae-Ryoung;Kim, Soon-Joo;Bang, Joon-Seok;La, Hyen-Oh
    • Korean Journal of Clinical Pharmacy
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    • v.19 no.1
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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.

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Evaluation of Chemotherapy Induced Peripheral Neuropathy by Cisplatin, Carboplatin and Oxaliplatin (Cisplatin, Carboplatin, Oxaliplatin 투여로 인한 말초신경병증에 대한 평가)

  • Yoon, Wan Ki;Heo, Mi Jung;Lee, Ok Sang;Lim, Sung Cil
    • Korean Journal of Clinical Pharmacy
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    • v.22 no.4
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    • pp.356-366
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    • 2012
  • Background: Chemotherapy-induced peripheral neuropathy (CIPN) involving sensory and motor nerve damage or dysfunction is a common and serious clinical problem that affects many patients receiving cancer treatment. This condition may pose challenges for the clinician to diagnose and manage, particularly in patients with coexisting conditions or disorders that involve the peripheral nervous system. Many chemotherapeutic agents used today are associated with the development of serious and dose-limiting CIPN that can adversely affect the administration of planned therapy and can impair quality of life by interference with the patients' activities of daily living. The most important clinical objective in the evaluation of patients with CIPN is to determine their level of functional impairment involving activities of daily living. These findings are used to make medical decisions to continue, modify, delay, or stop treatment. The most commonly reported drugs to cause CIPN include taxanes, platinum agents, vinca alkaloids, thalidomide, and bortezomib. We aimed to determine PN incidence during cisplatin, carboplatin and oxaliplatin administration. Methods: We collected data from 125 patients who received at least one cycle of cisplatin, carboplatin or oxaliplatin. They completed a self-reported questionnaire and items related to their disease and peripheral neuropathy. The investigators filled in part of items about disease and treatment. Patient Neurotoxicity Qeustionnaire developed by Bionumerik company were applied for PN assessment. Results: The incidences of sensory neurotoxicities of cisplatin, carboplatin and oxaliplatin were respectively 23%, 56% and 50%. The incidences of motor neurotoxicities of cisplatin, carboplatin and oxaliplatin were respectively 18%, 42% and 19%. The incidences of severe neurotoxicities of cisplatin, carboplatin and oxaliplatin were respectively 13%, 28% and 14%. The incidences of PN were associated with cumulative dose but not age, gender and concurrent illness. 19.2% of the patients (24/125) were prescribed with gabapentin, nortriptyline or gabapentin plus nortriptyline to reduce these peripheral symptoms and 75% of the patients answered the drug were effective. Conclusion: Incidence of PN after cisplatin or oxaliplatin administration is cumulative dose-related. Physician-based assessments under-reported the incidence and severity of CIPN. To overcome this limitation, diagnostic tools specifically designed to assess peripheral neuropathy severity associated with chemotherapy must be developed.

Prevalence of Oxaliplatin-induced Chronic Neuropathy and Influencing Factors in Patients with Colorectal Cancer in Iran

  • Shahriari-Ahmadi, Ali;Fahimi, Ali;Payandeh, Mehrdad;Sadeghi, Masoud
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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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.