Oxaliplatin: Mechanism of Action, Indications and Important Notes
Oxaliplatin is a cytostatic agent from the group of platinum compounds used in cancer therapy. It belongs to the third generation of platinum derivatives and differs in its chemical structure and spectrum of activity from the older platinum compounds cisplatin and carboplatin. Oxaliplatin works by damaging the DNA of cancer cells, thereby inhibiting their division. In the treatment of colorectal cancer, oxaliplatin has assumed a particularly important role and is a component of several well-established chemotherapy protocols.
Mechanism of Action
Oxaliplatin enters cells and is converted there to reactive platinum complexes. These complexes bind covalently to the cell's DNA, primarily causing cross-links (so-called adducts) within a single DNA strand and between two DNA strands. These cross-links damage the DNA so severely that the cell can no longer read or replicate it correctly. Cell division is halted and the cell is directed towards programmed cell death (apoptosis).
A key advantage of oxaliplatin over cisplatin is its efficacy in tumour cells that are resistant to cisplatin. This is due to different recognition and repair mechanisms for the respective DNA adducts: cisplatin adducts are recognised and removed by certain DNA repair systems, whereas oxaliplatin adducts are not, making them more effective in some tumour cells.
Oxaliplatin achieves its optimal effect in combination with other cytostatic agents, particularly 5-fluorouracil and folinic acid. These combinations are known under the designations FOLFOX (various variants) and are used as standard in colorectal cancer therapy.
Indications
Colorectal Carcinoma
The most important indication for oxaliplatin is colorectal carcinoma, i.e. cancer of the colon and rectum. Oxaliplatin is used:
- As adjuvant therapy after complete resection of stage III colorectal cancer (with lymph node involvement) to reduce the risk of recurrence
- For the treatment of metastatic colorectal carcinoma in combination with 5-fluorouracil and folinic acid (FOLFOX protocol) or in combination with capecitabine (XELOX protocol)
- In combination with other agents such as bevacizumab or cetuximab in metastatic disease, depending on the molecular pathological profile of the tumour
The evidence base for oxaliplatin in colorectal carcinoma is extensive and has led to its firm establishment in national and international treatment guidelines.
Other Tumour Entities
Outside its approved indication, oxaliplatin is used in some countries for other tumour types, including gastric carcinoma, pancreatic carcinoma, hepatocellular carcinoma and certain ovarian carcinomas. The evidence varies by indication and is evaluated by oncologists on a case-by-case basis.
Administration and Dosing
Oxaliplatin is administered exclusively intravenously as an infusion. It is available as a concentrate for the preparation of an infusion solution. The infusion typically lasts two to six hours. Dosing is based on the patient's body surface area and is expressed in mg per square metre. In the FOLFOX protocol, oxaliplatin is administered every two weeks. The exact dose and schedule are determined by the oncologist based on the treatment protocol and individual tolerability. Dose reductions may be necessary if side effects occur.
Note on Solubility
Oxaliplatin is unstable in saline solution and must be dissolved and administered in 5% glucose solution. Saline-containing infusion solutions lead to inactivation of the active substance and must not be used. Aluminium- or chloride-containing materials should also be avoided during preparation. These pharmaceutical particularities are observed by trained medical staff.
Characteristic Side Effect: Polyneuropathy
The best-known and clinically most relevant side effect of oxaliplatin is peripheral neuropathy, i.e. damage to the peripheral nerves. This occurs in two forms:
Acute Sensory Neuropathy
Shortly after the infusion, acute sensory symptoms can occur, particularly tingling, numbness or a painful cold sensation in the hands, feet and around the mouth. These symptoms are aggravated by cold and generally improve within hours to a few days after the infusion. Patients should avoid cold drinks and contact with cold objects for some time after the infusion.
Cumulative Chronic Neuropathy
With repeated administration of oxaliplatin, a cumulative chronic polyneuropathy can develop, manifesting as persistent sensory disturbances, tingling, reduced perception of touch and temperature, and coordination problems. These symptoms can significantly impair daily activities and quality of life. The neuropathy can persist after the end of therapy or may improve only slowly and incompletely. The cumulative total dose is an important factor in the extent of neuropathy. In cases of progressive neuropathy, a dose reduction or treatment break may become necessary.
Other Adverse Effects
- Nausea and vomiting are common and are treated concomitantly with antiemetics
- Diarrhoea may occur, particularly in combination with 5-fluorouracil
- Bone marrow suppression with reduction of white blood cells, red blood cells and platelets requires regular blood count monitoring
- Alopecia (hair loss) is less pronounced than with many other cytostatic agents
- Infusion reactions such as allergic reactions are possible and require medical monitoring during the infusion
- Hepatic dysfunction has been described, particularly with prolonged use
Oxaliplatin on Sanoliste
On Sanoliste you will find oncology centres and specialists in internal oncology who offer specialised care for the treatment of colorectal cancer and other tumour diseases. Chemotherapy with oxaliplatin requires specialised oncological support, close blood count monitoring and good communication between the patient and the medical team.
The information on this page is for general information purposes only and does not replace consultation with an oncologist. Oxaliplatin is a prescription-only medicine and is used exclusively in medical facilities under specialist supervision.
Frequently Asked Questions about Oxaliplatin
How can I alleviate cold sensitivity after an oxaliplatin infusion?
The acute cold sensitivity after oxaliplatin infusion results from temporary damage to nerve fibres, which is aggravated by cold. It is recommended to avoid ice-cold foods and drinks for a few days after the infusion, to wear gloves when handling cold objects, and to keep warm. Touching metal objects from the refrigerator should be avoided. These measures can significantly alleviate the symptoms. The treatment team should be informed of more severe complaints.
What is the FOLFOX protocol?
FOLFOX is the abbreviation for a chemotherapy protocol that combines folinic acid (FOL), 5-fluorouracil (F) and oxaliplatin (OX). There are various variants, such as FOLFOX4 and FOLFOX6, which differ slightly in dosages and method of administration. FOLFOX is administered every two weeks as a multi-hour infusion. The combination of the three active substances exploits different mechanisms of action: 5-fluorouracil and folinic acid inhibit DNA synthesis via thymidylate synthase, while oxaliplatin directly damages DNA. The combination acts synergistically.