Oxaliplatin
- Article Author:
- Bhavana Devanabanda
- Article Editor:
- Anup Kasi
- Updated:
- 10/27/2020 9:39:34 PM
- For CME on this topic:
- Oxaliplatin CME
- PubMed Link:
- Oxaliplatin
Indications
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:
- Advanced biliary adenocarcinoma in combination with capecitabine or gemcitabine.[10][11]
- Fludarabine refractory chronic lymphocytic leukemia in combination with fludarabine, cytarabine, and rituximab.[12]
- Esophageal and gastric cancers in combination with epirubicin or capecitabine or docetaxel, leucovorin, and fluorouracil.[13][14][15]
- Refractory neuroendocrine tumors in combination with capecitabine.[16]
- Refractory or relapsed non-Hodgkin Lymphoma in combination with gemcitabine and rituximab.[17]
- Advanced ovarian cancer.[18][
- Advanced pancreatic cancer in combination with capecitabine or fluorouracil, leucovorin, and irinotecan.[19][20]
- Refractory testicular cancer in combination with gemcitabine and paclitaxel.[21]
Mechanism of Action
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]
Administration
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]
Adverse Effects
The most common adverse drug effects reported with oxaliplatin monotherapy are:
- Systemic: fever, fatigue, nausea, emesis, weakness.[27][24]
- Nervous system: peripheral sensory neuropathy, pain, headache, insomnia.[28]
- Gastrointestinal system: diarrhea, abdominal pain, constipation, anorexia, stomatitis.[22]
- Hepatic: elevated serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin.[22]
- Hematologic and oncologic: anemia, thrombocytopenia, leukopenia.[22]
- Musculoskeletal: back pain[29]
- Respiratory system: dyspnea, cough.[27]
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:
- Baricitinib
- Disease-modifying anti-rheumatic drugs (DMARDs)
- Chloramphenicol
- Cladribine
- Clozapine
- Deferiprone
- Denosumab
- Dipyrone
- Echinacea
- Erdafitinib
- Fingolimod
- Fosphenytoin-Phenytoin
- Haloperidol
- Leflunomide
- Lenograstim
- Lipegfilgrastim
- Mesalamine
- Natalizumab
- Nivolumab
- Ocrelizumab
- Palifermin
- Pidotimod
- Pimecrolimus
- Promazine
- QT-prolonging agents
- Roflumilast
- Siponimod
- Sipuleucel-T
- Tacrolimus
- Tafenoquine
- Taxane derivatives
- Tertomotide
- Tofacitinib
- Topotecan
- Upadacitinib
- Vaccines
Contraindications
Oxaliplatin is contraindicated in patients who have/are:
Monitoring
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]
Toxicity
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]
Enhancing Healthcare Team Outcomes
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:
- Complete blood count, liver function tests, renal function tests, pregnancy test
- Proper administration of drug and monitoring of the IV site
- Monitoring toxicity
- Monitor the patient for signs and symptoms of CINV, peripheral sensory neuropathy, infection, GI disturbances
- Consult with the pharmacist and toxicologist regarding dosing
- Consult with the radiologist, pathologist, and surgeon regarding the spread of cancer
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.