Oxaliplatin

Oxaliplatin is a cytostatic drug (molecular formula: C8H14N2O4Pt) from the group of platinum analogues, belongs to a new class of platinum derivatives in which the platinum atom is complexed with 1,2-diaminocyclohexane (DACH) and an oxalate group. The substance interacts with DNA in a similar way to cisplatin and carboplatin, but inhibits DNA synthesis more strongly.

Oxaliplatin causes cross-linking in and between the DNA strands. The 1,2-diaminocyclohexane ligand (DACH ligand) influences the ability of the cell to tolerate DNA-platinum adducts. The DACH-platinum adducts formed from oxaliplatinum inhibit DNA synthesis more strongly than the cis-diamino-platinum adducts formed from cis- and carboplatinum.

The recommended dose for oxaliplatin in the treatment of metastatic colorectal cancer is 85 mg/m2 body surface area (KOF) intravenously every 2 weeks until disease progression or until the tolerance limit is reached.

The most common side effects of Oxaliplatin in combination with 5-fluorouracil and folinic acid are diarrhea, nausea, vomiting and inflammation of the mucous membranes, changes in blood count and peripheral sensory neuropathy (often dose-limiting). In detail, the following organ ADRs can be observed with varying frequency and severity:

• Diseases of the blood and lymphatic system: anaemia, neutropenia, thrombocytopenia, leucopenia, lymphopenia, febrile neutropenia, haemolytic anaemia. Furthermore, oxaliplatin can rarely induce immune-mediated thrombocytopenia and rarely immune-mediated pancytopenia.
• Metabolic and nutritional disorders: anorexia, hyperglycaemia, hypokalemia, hypernatremia, dehydration, hypocalcaemia, metabolic acidosis
• Psychiatric disorders: depression, insomnia Nervousness
• Diseases of the nervous system: headache, dizziness, motor neuritis, meningism, dysarthria, reversible posterior leukoencephalopathy syndrome (RPLS or PRES). Peripheral sensory neuropathy with oxaliplatin-induced cold hyperalgesia: this is often accompanied by painful sensations and can be aggravated by banal touching of colder metal or drinking chilled beverages. The voltage-dependent sodium channel subtype 1.6 (V1.6) plays a decisive role in this case. After exposure to oxaliplatin, action potentials accumulate at nerve fibres. This increased transmission of information triggers the sensations. In cold weather, sensations are also triggered in the nose and ears.
• Eye diseases: conjunctivitis, visual disturbances temporary reduction of vision, disturbances of the visual field, optic neuritis, temporary loss of vision (reversible after interruption of therapy)
• Diseases of the ear and labyrinth: Ototoxicity (occasional)
• respiratory, thoracic and mediastinal diseases: dyspnea, cough, nosebleed (very frequent), hiccups, pulmonary embolism (frequent), interstitial lung diseases (occasional)
• Diseases of the gastrointestinal tract: hyperlipidemia, diarrhoea, vomiting, stomatitis/mucositis, constipation (very frequent), intestinal bleeding (frequent), colitis including clostridium difficile diarrhoea, pancreatitis (occasional).
• Skin and subcutaneous tissue diseases: alopecia (very common); hand-foot syndrome, exanthema, hyperhidrosis, onycholysis (frequent). A hypersensitivity reaction to oxaliplatin is rare. This is a serious side effect that includes symptoms such as facial flushing, erythema, itching, fever, tachycardia, dyspnea, swelling of the tongue, headache, chills, weakness, nausea, dizziness and edema (Syrigou EI et al. 2009).
• Diseases of the blood and lymphatic system: rare (≥ 1/10,000, < 1/1,000): Disseminated intravascular coagulation (DIC ), including fatal cases
• Other side effects (individual observations): haemolytic uremic syndrome, autoimmune pancytopenia; secondary leukaemia

Oxaliplatin is included in all guidelines for the therapy of colorectal cancer for the respective indication areas with the highest recommendation level.

Oxaliplatin is used in combination with 5-fluorouracil (5-FU) and folinic acid (FA) (so-called FOLFOX4 regimen). The cytostatic drug is approved:

- for the adjuvant treatment of stage III colon carcinoma (Dukes C) after complete removal of the primary tumour,

- for the treatment of metastatic colorectal cancer.

1. Dasari S et al (2014) Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol 740:364-78 https://pubmed.ncbi.nlm.nih.gov/25058905/
2. Nakagawa T et al (2017) Roles of Transient Receptor Potential Ankyrin 1 in Oxaliplatin-Induced Peripheral Neuropathy. Biol Pharm Bull 40:947-953.
3. Powder JN et al (2017) Factors associated with the development and severity of oxaliplatin-induced peripheral neuropathy: a systematic review. Asia Pac J Clin Oncol 13:345-355.
4. Stojanovska V et al (2019) Oxaliplatin Treatment Alters Systemic Immune Responses. Biomed Res Int: 4650695. doi: 10.1155/2019/4650695.
5. Syrigou EI et al (2009) Hypersensitivity reactions to oxaliplatin: a retrospective study and the development of a desensitization protocol. Clin Colorectal Cancer 8:106-109.
6. Stojanovska V et al. (2019) Oxaliplatin Treatment Alters Systemic Immune Responses. Biomed Res Int: 4650695. doi: 10.1155/2019/4650695