Oxaliplatin is an FDA approved platinum-based antineoplastic medication.[1] It is indicated in the adjunctive treatment of stage III colorectal cancer after resection of the primary tumor and for the treatment of metastatic colorectal cancer.[1][2] It is FDA approved in combination with infusional 5-fluorouracil and leucovorin.[1]
In the pediatric population, oxaliplatin is used for treating refractory or relapsed solid tumors in combination with etoposide or ifosfamide or gemcitabine or irinotecan or fluorouracil and leucovorin.[3][4][5][6][7] Oxaliplatin is also used to treat refractory or relapsed neuroblastoma in combination with doxorubicin.[8][9]
The following are the off-label indications for oxaliplatin:
Oxaliplatin is an alkylating agent and has non-cell cycle specific cytotoxicity.[1] The platinum complex in the drug binds to DNA and forms cross-links.[22] The cross-links inhibit DNA replication, transcription, and arrest of cell-cycle, resulting in cell death.[22] It works synergistically with fluoropyrimidines such as 5-fluorouracil.[1] Oxaliplatin is effective in treating fast-growing tumors like those in the gastrointestinal system, which have a high cell turnover rate.[22]
Oxaliplatin administration is via intravenous infusion (IV) over two hours.[23] In the event of acute toxicity, the administration is extended to 6 hours.[23] The recommended infusion rate is 1mg/m^2/minute or 85 mg/m^2 dose over 85 minutes every two weeks.[23] Oxaliplatin is moderately emetogenic.[24] To prevent chemotherapy-induced nausea and vomiting (CINV), pretreatment with antiemetics is strongly recommended.[24]
Before administration, ensure proper placement of needle and catheter to prevent extravasation and flush the infusion line with D5W.[25] It is common for patients to have vascular pain near the site of IV infusion, pretreatment with fast-acting oxycodone is a recommendation.[26] Monitor the IV site for irritation, redness, pain, and swelling.[26] In the event of extravasation, immediately discontinue treatment, remove the infusion line, aspirate the solution, do not flush, elevate the site and place a warm compress over the infusion site.[25] Do not use a cold compress as it can cause acute neurological symptoms.[25]
The most common adverse drug effects reported with oxaliplatin monotherapy are:
Drug interactions: Oxaliplatin requires close monitoring when administered with other drugs as it can enhance the adverse/toxic effects or diminish the therapeutic effects. The following drug interactions are important to consider:
Oxaliplatin is contraindicated in patients who have/are:
Patients on oxaliplatin therapy must periodically have blood and urine work up to assess complete blood count with differential, basic metabolic panel, liver function tests, renal function tests, and electrocardiogram (ECG) for QT prolongation.[22] It is essential to do a pregnancy test in women of reproductive age before initiating treatment.[22]
Oxaliplatin has a narrow therapeutic index, which most commonly affects the hematopoietic system, nervous system, and has gastrointestinal side effects.[22] Periodic neurological exams are a recommendation to assess for acute or chronic oxaliplatin-induced peripheral neuropathy[22]
No known antidote exists for oxaliplatin overdose. Oxaliplatin has dose-dependent toxicity on the hematopoietic system. It causes myelosuppression, anemia, and thrombocytopenia.[22] In rare cases with repeated oxaliplatin treatment hypersensitivity reactions, hemolytic anemia and secondary immune thrombocytopenia can occur.[22] The treatment is discontinuation and symptomatic management.[22]
Oxaliplatin has dose-limiting toxicity on the nervous system.[22] It can cause acute or chronic peripheral neuropathy.[22] Acute oxaliplatin-induced peripheral neuropathy presents with paresthesia, dysesthesias, or allodynia usually around the mouth and throat during or after the treatment.[22] Exposure to cold can also trigger these symptoms.[22] The symptoms resolve within a few hours to days following discontinuation.[31] Additional precautions are possible by prolonging the infusion time from two hours to six hours.[31]
Repeated oxaliplatin treatment can result in chronic peripheral neuropathy.[22] It manifests in the distal extremities with paresthesia, hypoesthesia, dysesthesia, and decreased proprioception.[22] It is seen in 10% of patients who receive a cumulative dose of 780 mg/m^2 (9 doses of 85mg/m^2) and in 50% of patients who receive a cumulative dose of 1170 mg/m^2 (13 doses).[31] One study has shown a decreased incidence of neurotoxicity in patients receiving supplemental infusions of calcium and magnesium on the day of oxaliplatin administration.[31] There is preliminary and conflicting data on the use of oral n-acetylcysteine, xaliproden, gabapentin, carbamazepine, amifostine, and glutathione in the prevention or amelioration of oxaliplatin-induced neuropathy.[31]
Multidisciplinary treatment teams consisting of a nurse, laboratory technologists, pharmacists, and physicians in different specialties need to be knowledgeable about the drug oxaliplatin. This team approach ensures proper administration, management, monitoring, and limitation of the adverse effects. When a patient is on a chemotherapeutic regimen, the pharmacist needs to communicate possible drug interactions and the recommended therapeutic dosage to the physician. The assigned nurse must monitor the IV site, be cognizant of the adverse effects of the drug, and relay them to the clinician. Lastly, the clinician must have enough information to determine if the patient is a candidate to receive a drug like oxaliplatin, given their medical history. The interpersonal healthcare team is responsible for the following:
The prevention and management of oxaliplatin-induced neurotoxicity start with the patient limiting exposure to cold environments, ensuring proper protection, and staying away from cold food and beverages.[22] One study has shown a decrease in neurotoxicity in patients who received infusions of calcium and magnesium before or after oxaliplatin administration.[37] [Level 2] In addition to changing the dosage, the interprofessional treatment team may consider supplementing oxaliplatin with calcium or magnesium in the event of peripheral sensory neuropathy.
[1] | Meyerhardt JA,Mayer RJ, Systemic therapy for colorectal cancer. The New England journal of medicine. 2005 Feb 3; [PubMed PMID: 15689586] |
[2] | Noepel-Duennebacke S,Arnold D,Hertel J,Tannapfel A,Hinke A,Hegewisch-Becker S,Reinacher-Schick A, Impact of the Localization of the Primary Tumor and RAS/BRAF Mutational Status on Maintenance Strategies After First-line Oxaliplatin, Fluoropyrimidine, and Bevacizumab in Metastatic Colorectal Cancer: Results From the AIO 0207 Trial. Clinical colorectal cancer. 2018 Dec; [PubMed PMID: 30145148] |
[3] | Lam CG,Furman WL,Wang C,Spunt SL,Wu J,Ivy P,Santana VM,McGregor LM, Phase I clinical trial of ifosfamide, oxaliplatin, and etoposide (IOE) in pediatric patients with refractory solid tumors. Journal of pediatric hematology/oncology. 2015 Jan; [PubMed PMID: 24942022] |
[4] | McGregor LM,Spunt SL,Santana VM,Stewart CF,Ward DA,Watkins A,Laningham FH,Ivy P,Furman WL,Fouladi M, Phase 1 study of an oxaliplatin and etoposide regimen in pediatric patients with recurrent solid tumors. Cancer. 2009 Feb 1; [PubMed PMID: 19117350] |
[5] | Geoerger B,Chisholm J,Le Deley MC,Gentet JC,Zwaan CM,Dias N,Jaspan T,Mc Hugh K,Couanet D,Hain S,Devos A,Riccardi R,Cesare C,Boos J,Frappaz D,Leblond P,Aerts I,Vassal G, Phase II study of gemcitabine combined with oxaliplatin in relapsed or refractory paediatric solid malignancies: An innovative therapy for children with Cancer European Consortium Study. European journal of cancer (Oxford, England : 1990). 2011 Jan; [PubMed PMID: 20943374] |
[6] | Macy ME,Duncan T,Whitlock J,Hunger SP,Boklan J,Narendren A,Herzog C,Arceci RJ,Bagatell R,Trippett T,Christians U,Rolla K,Ivy SP,Gore L, A multi-center phase Ib study of oxaliplatin (NSC [PubMed PMID: 23024067] |
[7] | Hartmann C,Weinel P,Schmid H,Grigull L,Sander A,Linderkamp C,Welte K,Reinhardt D, Oxaliplatin, irinotecan, and gemcitabine: a novel combination in the therapy of progressed, relapsed, or refractory tumors in children. Journal of pediatric hematology/oncology. 2011 Jul; [PubMed PMID: 21572345] |
[8] | Mascarenhas L,Malogolowkin M,Armenian SH,Sposto R,Venkatramani R, A phase I study of oxaliplatin and doxorubicin in pediatric patients with relapsed or refractory extracranial non-hematopoietic solid tumors. Pediatric blood [PubMed PMID: 23335436] |
[9] | Tran HC,Marachelian A,Venkatramani R,Jubran RF,Mascarenhas L, Oxaliplatin and Doxorubicin for relapsed or refractory high-risk neuroblastoma. Pediatric hematology and oncology. 2015 Feb; [PubMed PMID: 25551355] |
[10] | André T,Boni C,Mounedji-Boudiaf L,Navarro M,Tabernero J,Hickish T,Topham C,Zaninelli M,Clingan P,Bridgewater J,Tabah-Fisch I,de Gramont A, Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. The New England journal of medicine. 2004 Jun 3; [PubMed PMID: 15175436] |
[11] | Nehls O,Oettle H,Hartmann JT,Hofheinz RD,Hass HG,Horger MS,Koppenhöfer U,Hochhaus A,Stieler J,Trojan J,Gregor M,Klump B, Capecitabine plus oxaliplatin as first-line treatment in patients with advanced biliary system adenocarcinoma: a prospective multicentre phase II trial. British journal of cancer. 2008 Jan 29; [PubMed PMID: 18182984] |
[12] | Tsimberidou AM,Wierda WG,Plunkett W,Kurzrock R,O'Brien S,Wen S,Ferrajoli A,Ravandi-Kashani F,Garcia-Manero G,Estrov Z,Kipps TJ,Brown JR,Fiorentino A,Lerner S,Kantarjian HM,Keating MJ, Phase I-II study of oxaliplatin, fludarabine, cytarabine, and rituximab combination therapy in patients with Richter's syndrome or fludarabine-refractory chronic lymphocytic leukemia. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2008 Jan 10; [PubMed PMID: 18182662] |
[13] | Cunningham D,Starling N,Rao S,Iveson T,Nicolson M,Coxon F,Middleton G,Daniel F,Oates J,Norman AR, Capecitabine and oxaliplatin for advanced esophagogastric cancer. The New England journal of medicine. 2008 Jan 3; [PubMed PMID: 18172173] |
[14] | Al-Batran SE,Hartmann JT,Hofheinz R,Homann N,Rethwisch V,Probst S,Stoehlmacher J,Clemens MR,Mahlberg R,Fritz M,Seipelt G,Sievert M,Pauligk C,Atmaca A,Jäger E, Biweekly fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for patients with metastatic adenocarcinoma of the stomach or esophagogastric junction: a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie. Annals of oncology : official journal of the European Society for Medical Oncology. 2008 Nov; [PubMed PMID: 18669868] |
[15] | Conroy T,Yataghène Y,Etienne PL,Michel P,Senellart H,Raoul JL,Mineur L,Rives M,Mirabel X,Lamezec B,Rio E,Le Prisé E,Peiffert D,Adenis A, Phase II randomised trial of chemoradiotherapy with FOLFOX4 or cisplatin plus fluorouracil in oesophageal cancer. British journal of cancer. 2010 Oct 26; [PubMed PMID: 20940718] |
[16] | Bajetta E,Catena L,Procopio G,De Dosso S,Bichisao E,Ferrari L,Martinetti A,Platania M,Verzoni E,Formisano B,Bajetta R, Are capecitabine and oxaliplatin (XELOX) suitable treatments for progressing low-grade and high-grade neuroendocrine tumours? Cancer chemotherapy and pharmacology. 2007 Apr; [PubMed PMID: 16937105] |
[17] | López A,Gutiérrez A,Palacios A,Blancas I,Navarrete M,Morey M,Perelló A,Alarcón J,Martínez J,Rodríguez J, GEMOX-R regimen is a highly effective salvage regimen in patients with refractory/relapsing diffuse large-cell lymphoma: a phase II study. European journal of haematology. 2008 Feb; [PubMed PMID: 18005385] |
[18] | Dieras V,Bougnoux P,Petit T,Chollet P,Beuzeboc P,Borel C,Husseini F,Goupil A,Kerbrat P,Misset JL,Bensmaïne MA,Tabah-Fisch I,Pouillart P, Multicentre phase II study of oxaliplatin as a single-agent in cisplatin/carboplatin /- taxane-pretreated ovarian cancer patients. Annals of oncology : official journal of the European Society for Medical Oncology. 2002 Feb; [PubMed PMID: 11886003] |
[19] | Xiong HQ,Varadhachary GR,Blais JC,Hess KR,Abbruzzese JL,Wolff RA, Phase 2 trial of oxaliplatin plus capecitabine (XELOX) as second-line therapy for patients with advanced pancreatic cancer. Cancer. 2008 Oct 15; [PubMed PMID: 18756532] |
[20] | Conroy T,Desseigne F,Ychou M,Bouché O,Guimbaud R,Bécouarn Y,Adenis A,Raoul JL,Gourgou-Bourgade S,de la Fouchardière C,Bennouna J,Bachet JB,Khemissa-Akouz F,Péré-Vergé D,Delbaldo C,Assenat E,Chauffert B,Michel P,Montoto-Grillot C,Ducreux M, FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. The New England journal of medicine. 2011 May 12; [PubMed PMID: 21561347] |
[21] | Bokemeyer C,Oechsle K,Honecker F,Mayer F,Hartmann JT,Waller CF,Böhlke I,Kollmannsberger C, Combination chemotherapy with gemcitabine, oxaliplatin, and paclitaxel in patients with cisplatin-refractory or multiply relapsed germ-cell tumors: a study of the German Testicular Cancer Study Group. Annals of oncology : official journal of the European Society for Medical Oncology. 2008 Mar; [PubMed PMID: 18006893] |
[22] | Alcindor T,Beauger N, Oxaliplatin: a review in the era of molecularly targeted therapy. Current oncology (Toronto, Ont.). 2011 Jan; [PubMed PMID: 21331278] |
[23] | Cercek A,Park V,Yaeger R,Reidy-Lagunes D,Kemeny NE,Stadler ZK,Segal NH,Varghese A,Saltz LB, Faster FOLFOX: Oxaliplatin Can Be Safely Infused at a Rate of 1 mg/m2/min. Journal of oncology practice. 2016 May; [PubMed PMID: 27072569] |
[24] | Hatakeyama S,Suzuki N,Abe K,Konno N,Kaneko T,Toyoguchi T,Shiraishi T, [Effects of Serum Sodium Concentrations on Nausea and Vomiting after Moderately Emetogenic Chemotherapy]. Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan. 2018; [PubMed PMID: 30068850] |
[25] | de Lemos ML,Walisser S, Management of extravasation of oxaliplatin. Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 2005 Dec; [PubMed PMID: 16595069] |
[26] | Suga Y,Ikeda N,Maeda M,Staub AY,Shimada T,Yonezawa M,Kitade H,Katsura H,Okada M,Ishizaki J,Sai Y,Matsushita R, Risk factors for oxaliplatin-induced vascular pain in patients with colorectal cancer and comparison of the efficacy of preventive methods. Journal of pharmaceutical health care and sciences. 2018; [PubMed PMID: 30094053] |
[27] | Khurana A,Mitsis D,Kowlgi GN,Holle LM,Clement JM, Atypical presentation of fever as hypersensitivity reaction to oxaliplatin. Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 2016 Apr; [PubMed PMID: 25361599] |
[28] | Saif MW,Reardon J, Management of oxaliplatin-induced peripheral neuropathy. Therapeutics and clinical risk management. 2005 Dec; [PubMed PMID: 18360567] |
[29] | Kurk SA,Peeters PHM,Dorresteijn B,de Jong PA,Jourdan M,Kuijf HJ,Punt CJA,Koopman M,May AM, Impact of different palliative systemic treatments on skeletal muscle mass in metastatic colorectal cancer patients. Journal of cachexia, sarcopenia and muscle. 2018 Oct; [PubMed PMID: 30144305] |
[30] | Sharief U,Perry DJ, Delayed reversible posterior encephalopathy syndrome following chemotherapy with oxaliplatin. Clinical colorectal cancer. 2009 Jul; [PubMed PMID: 19632931] |
[31] | Cersosimo RJ, Oxaliplatin-associated neuropathy: a review. The Annals of pharmacotherapy. 2005 Jan; [PubMed PMID: 15590869] |
[32] | Takimoto CH,Remick SC,Sharma S,Mani S,Ramanathan RK,Doroshow JH,Hamilton A,Mulkerin D,Graham M,Lockwood GF,Ivy P,Egorin M,Greenslade D,Goetz A,Grem JL, Administration of oxaliplatin to patients with renal dysfunction: a preliminary report of the national cancer institute organ dysfunction working group. Seminars in oncology. 2003 Aug; [PubMed PMID: 14523791] |
[33] | Ryu CG,Jung EJ,Kim G,Kim SR,Hwang DY, Oxaliplatin-induced Pulmonary Fibrosis: Two Case Reports. Journal of the Korean Society of Coloproctology. 2011 Oct; [PubMed PMID: 22102978] |
[34] | Pissarra A,Malheiro M,Matos LV,Plácido AN, Severe rhabdomyolysis related to oxaliplatin adjuvant therapy for colorectal cancer. BMJ case reports. 2019 Apr 16; [PubMed PMID: 30996068] |
[35] | Janinis J,Papakostas P,Samelis G,Skarlos D,Papagianopoulos P,Fountzilas G, Second-line chemotherapy with weekly oxaliplatin and high-dose 5-fluorouracil with folinic acid in metastatic colorectal carcinoma: a Hellenic Cooperative Oncology Group (HeCOG) phase II feasibility study. Annals of oncology : official journal of the European Society for Medical Oncology. 2000 Feb; [PubMed PMID: 10761750] |
[36] | Rogers JE,Dasari A,Eng C, The Treatment of Colorectal Cancer During Pregnancy: Cytotoxic Chemotherapy and Targeted Therapy Challenges. The oncologist. 2016 May; [PubMed PMID: 27000464] |
[37] | Gamelin L,Boisdron-Celle M,Delva R,Guérin-Meyer V,Ifrah N,Morel A,Gamelin E, Prevention of oxaliplatin-related neurotoxicity by calcium and magnesium infusions: a retrospective study of 161 patients receiving oxaliplatin combined with 5-Fluorouracil and leucovorin for advanced colorectal cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 2004 Jun 15; [PubMed PMID: 15217938] |