Oxaliplatin undergoes nonenzymatic conversion in physiologic solutions to active derivatives via displacement of the labile oxalate ligand. Several transient reactive species are formed, including monoaquo and diaquo DACH platinum, which covalently bind with acromolecules. Both interand intrastrand Pt-DNA crosslinks are formed. Crosslinks are formed between the N7 positions of two adjacent guanines (GG), adjacent adenine-guanines (AG), and guanines separated by an intervening nucleotide (GNG). These crosslinks inhibit DNA replication and transcription. Cytotoxicity is cell-cycle nonspecific. In vivo studies have shown antitumor activity of oxaliplatin against colon carcinoma. In combination with fluorouracil, oxaliplatin exhibits in vitro and in vivo antiproliferative activity greater than either compound alone in several tumor models (HT29 [colon], GR [mammary], and L1210 [leukemia]).

ELOXATIN is a platinum-based drug used in combination with infusional fluorouracil and leucovorin, which is indicated for:
•adjuvant treatment of stage III colon cancer in patients who have undergone complete resection of the primary tumor.
•treatment of advanced colorectal cancer.

•Administer ELOXATIN 85 mg/m2 as an intravenous infusion over 120 minutes concurrently with leucovorin over 120 minutes in separate bags, followed by fluorouracil on Day 1 of each 14-day cycle. Administer fluorouracil and leucovorin on Day 2 as recommended. (2.1)
•Adjuvant Treatment: Continue treatment for up to 12 cycles or unacceptable toxicity.
•Advanced Colorectal Cancer: Continue treatment until disease progression or unacceptable toxicity.

Most common adverse reactions (incidence greater than or equal to 40%) were peripheral sensory neuropathy, neutropenia, thrombocytopenia, anemia, nausea, increase in transaminases and alkaline phosphatase, diarrhea, emesis, fatigue, and stomatitis.

History of hypersensitivity reaction to oxaliplatin or other platinum-based drugs.

•Peripheral Sensory Neuropathy: Acute and delayed neuropathy can occur. Avoid topical application of ice. Reduce the dose or permanently discontinue ELOXATIN as recommended.
•Severe Myelosuppression: Delay ELOXATIN until neutrophils are greater than or equal to 1.5 × 109 /L and platelets are greater than or equal to 75 × 109 /L. Withhold ELOXATIN for sepsis or septic shock. Dose reduce after recovery from grade 4 neutropenia, febrile neutropenia, or grade 3-4 thrombocytopenia as recommended. See package insert for complete information.