Oxaliplatin is a platinum-based antineoplastic agent that is used in cancer chemotherapy
Mechanism of Action
The cytotoxicity of platinum compounds is thought to result from inhibition of DNA synthesis in cancer cells. In vivo studies showed that Oxaliplatin has anti-tumor activity against colon carcinoma through its (non-targeted) cytotoxic effects.
Oxaliplatin functions by forming both inter- and intra- strand cross links in DNA. Cross links in DNA prevent DNA replication and transcription, resulting in cell death.
Oxaliplatin is typically administered with fluorouracil and leucovorin in a combination known as FOLFOX for the treatment of colorectal cancer. There are generic equivalents on the market now Oxaliplatin has been compared with other platinum compounds (Cisplatin, Carboplatin) in advanced cancers (gastric, ovarian).
Advanced Colorectal Cancer
In clinical studies, Oxaliplatin by itself has modest activity against advanced colorectal cancer.It has been extensively studied in combination with Fluorouracil and Folinic Acid (a combination known as FOLFOX). When compared with fluorouracil and folinic acid administered according to the “De Gramont regimen” there was no significant increase in overall survival with the FOLFOX regimen (specifically, FOLFOX4), but progression-free survival, the primary end-point of the phase III randomized trial, was improved with FOLFOX
Adjuvant Treatment Of Colorectal Cancer
After the curative resection of colorectal cancer, chemotherapy based on Fluorouracil and folinic acid reduces the risk of relapse. The benefit is clinically relevant when cancer has spread to locoregional lymph nodes (stage III, Dukes C). The addition of Oxaliplatin improves relapse-free survival, but data on overall survival have not yet been published in extenso. When cancer has not spread to the locoregional lymph nodes (stage II, Dukes B) the benefit of chemotherapy is marginal and the decision on whether to give adjuvant chemotherapy should be carefully evaluated by discussing with the patient the realistic benefits and the possible toxic side effects of treatment. This is even more relevant when the oncologist proposes treatment with Oxaliplatin.
Side-effects of oxaliplatin treatment can potentially includ
- Neuropathy, (both an acute, reversible sensitivity to cold and numbness in the hands and feet and a chronic, possibly irreversible foot/leg, hand/arm numbness, often with deficits in proprioception)
- Nausea, vomiting, and/or diarrhea
- Neutropenia (low number of a type of white blood cells)
- Ototoxicity (hearing loss)
- Extravasation if Oxaliplatin leaks from the infusion vein it may cause severe damage to the connective tissues.
- Hypokalemia (low blood potassium), which is more common in women than men
- In addition, some patients may experience an allergic reaction to platinum-containing drugs.
- This is more common in women.
- Oxaliplatin has less ototoxicity and nephrotoxicity than cisplatin and carboplatin