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      Increase in spleen volume as a predictor of oxaliplatin toxicity

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          Oxaliplatin is a nonconventional third-generation platinum compound. It is an important chemotherapeutic agent in regimens used in gastrointestinal carcinomas as well as other malignancies. Oxaliplatin toxicity profile includes neurotoxicity, hepatotoxicity, and splenomegaly. The primary aim of this study was to measure the spleen volume of patients on oxaliplatin therapy before and during chemotherapy to detect any increase in splenic size as a biomarker for early oxaliplatin toxicity.


          This was a prospective pilot study conducted at the American University of Beirut-Medical Center. Fifty patients newly started on oxaliplatin were included. The spleen volume was measured from the patients’ baseline CT scan using the IntelliSpace Portal upgraded system (using Response Evaluation Criteria In Solid Tumors [RECIST]), for each follow-up CT scan. Side effects were evaluated at each patient visit and graded according to the severity.


          Thirty-seven (74%) patients developed an increase in spleen size. Thirty-three (66%) sampled patients developed peripheral neuropathy (all grades) at 3 months, whereas only two (4%) patients developed grade 3 neuropathy. Only one (3%) patient who developed an increase in spleen size also developed grade 3 peripheral neuropathy – a result that is significantly different ( p<0.001) when comparing patients with an increase in spleen size who also developed peripheral neuropathy of other grades.


          An increase in spleen volume possibly precedes a significant peripheral neuropathy which could be a potential marker for oxaliplatin-induced toxicity.

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          Capecitabine (Xeloda) in combination with oxaliplatin: a phase I, dose-escalation study in patients with advanced or metastatic solid tumors.

          This phase I, dose-escalation study was conducted to determine the recommended dose of intermittent oral capecitabine in combination with a fixed dose of i.v. oxaliplatin. Secondary objectives included evaluation of the safety profile and antitumor activity. Twenty-three patients with advanced or metastatic solid tumors received a 21-day regimen of oral capecitabine (500, 825, 1000 or 1250 mg/m2 twice daily, days 1-14) in combination with oxaliplatin (130 mg/m2, 2-h i.v. infusion, day 1). Dose-limiting toxicities were determined during the first treatment cycle, and safety and efficacy were evaluated throughout treatment. The recommended dosing schedule is oral capecitabine 1000 mg/m2 twice daily (days 1-14) with i.v. oxaliplatin 130 mg/m2 (day 1) in a 21-day treatment cycle. The principal dose-limiting toxicity was diarrhea. The most frequent treatment-related adverse events occurring during the study were gastrointestinal (nausea/vomiting, diarrhea) and neurological (dysesthesia, paresthesia). The majority of treatment-related adverse events were mild to moderate in intensity, and no grade 4 adverse events occurred in the 15 patients treated at or below the recommended dose. The most common grade 3/4 laboratory abnormalities were lymphocytopenia (52% of patients), thrombocytopenia (22%; grade 3 only), neutropenia (17%) and hyperbilirubinemia (17%). Among patients treated at or below the recommended dose level (n = 15), only two patients experienced grade 3 neutropenia and no patients experienced grade 4 neutropenia. Partial tumor responses occurred in six patients (26%), including five of nine patients (55%) with colorectal cancer. All responding patients were pretreated with 5-fluorouracil and four responders had received prior irinotecan. Oral capecitabine with i.v. oxaliplatin is a feasible combination regimen that shows promising antitumor activity in patients with colorectal cancer. There is an ongoing, phase II study to further characterize the safety and efficacy of this combination as first-line therapy for metastatic colorectal cancer, using the recommended dose identified in this study.
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            Oxaliplatin-related thrombocytopenia.

            Oxaliplatin is a third generation platinum compound that inhibits DNA synthesis, mainly through intrastrandal cross-links in DNA. Most of the experience with the clinical use of this drug is derived from colorectal cancer but it is also used in other tumor types such as ovary, breast, liver and non-Hodgkin's lymphoma. Thrombocytopenia is a frequent toxicity seen during oxaliplatin treatment, occurring at any grade in up to 70% of patients and leading to delays or even discontinuation of the chemotherapy. Although myelossupression is recognized as the main cause of oxaliplatin-related thrombocytopenia, new mechanisms for this side-effect have emerged, including splenic sequestration of platelets related to oxaliplatin-induced liver damage and immune thrombocytopenia. These new pathophysiology pathways have different clinical presentations and evolution and may need specific therapeutic maneuvers. This article attempts to review this topic and provides useful clinical information for the management of oxaliplatin-related thrombocytopenia.
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              Effect of preoperative chemotherapy on liver resection for colorectal liver metastases.

              To compare the effects of preoperative chemotherapy on liver parenchyma morphology, as well as morbidity and mortality after liver resection for colorectal liver metastases. Prospectively collected data on 173 patients undergoing liver resection for CLM between 1/2003 and 9/2005 was analysed in three groups: A: preoperative oxaliplatin (Ox, n=70); B: other chemotherapeutic agents (OC, n=60); and C: surgery alone without chemotherapy (SA, n=43). Blood transfusion, hospital stay, operative procedure, peak postoperative bilirubin levels, complications and histopathology of the resected liver were compared. Intra-operative blood transfusion requirement (34%) and biliary complications (16%) was higher in patients receiving oxaliplatin-based chemotherapy (p=0.01 and p=0.06, respectively). Oxaliplatin-based chemotherapy was also associated with sinusoidal dilatation of mild grade in 52.8% vs. 26.6% and 23.3% patients (p=0.007 and p=0.004) in other groups, respectively. Steatosis was similarly distributed across the study group. Postoperative mortality was 2, 1 and 4 patients, respectively (p=ns). Oxaliplatin-based preoperative chemotherapy is associated with vascular alterations in the liver parenchyma without significantly increasing the risk of steatosis, or postoperative morbidity and mortality.

                Author and article information

                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                11 April 2018
                : 14
                : 653-657
                [1 ]Department of Internal Medicine, Division of Hematology-Oncology, American University of Beirut-Medical Center, Beirut, Lebanon
                [2 ]Department of Diagnostic Radiology, American University of Beirut-Medical Center, Beirut, Lebanon
                [3 ]Department of Radiation Oncology, American University of Beirut-Medical Center, Beirut, Lebanon
                Author notes
                Correspondence: Ali Shamseddine, Department of Internal Medicine, Division of Hematology-Oncology, American University of Beirut-Medical Center, Beirut, Lebanon, PO Box 11-0236, Riad El Solh 110 72020, Beirut, Lebanon, Tel +961 1 374 374, Fax +961 1 370 814, Email as04@ 123456aub.edu.lb
                © 2018 El Chediak et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Original Research


                oxaliplatin, toxicity, neuropathy, splenomegaly, hepatic sinusoidal injury


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