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Platinum compoundsIn useDerivative of an earlier drugNeeds review

Oxaliplatin

Also known as Eloxatin

A platinum drug of the diaminocyclohexane (DACH) family, given by infusion with fluorouracil and folinic acid. FDA approvals cover advanced colorectal cancer and adjuvant treatment of stage III colon cancer.

From discovery to approval

  1. c. 1978 · First described

    In 1978 Kidani and colleagues reported platinum complexes of 1,2-diaminocyclohexane (DACH), the carrier-ligand family of oxaliplatin, as highly active against ascites sarcoma-180. The abstract does not name oxaliplatin; its best compound was oxalato(cis-1,2-diaminocyclohexane)platinum, while the 2002 label gives oxaliplatin's ligand as the (1R,2R) isomer.[2][3][4][1]

  2. 2002-08-09 · FDA accelerated · 24 years after first description

    In combination with infusional 5-FU/LV for metastatic carcinoma of the colon or rectum that recurred or progressed during or within 6 months of first-line bolus 5-FU/LV plus irinotecan. The label states approval was based on response rate and an interim analysis of time to radiographic progression; the January 2004 letter states the approval was granted under accelerated-approval regulations.[5]

  3. 2004-01-09 · FDA converted · 26 years after first description

    In combination with infusional 5-FU/LV for patients previously untreated for advanced colorectal cancer. The letter states this approval fulfils Commitment #3 made under 21 CFR 314.510; it does not use the word converted.[5]

  4. 2004-11-04 · FDA regular · 26 years after first description

    In combination with infusional 5-FU/LV for adjuvant treatment of stage III colon cancer after complete resection of the primary tumour, based on improved disease-free survival with no demonstrated overall survival benefit after a median follow-up of 4 years. The type regular is an inference: the letter has no accelerated-approval wording.[6]

How it works

In the body the oxalate group is displaced, producing reactive platinum-DACH species that form cross-links within and between DNA strands, mainly at guanine and adenine bases. These block DNA replication and transcription, in all phases of the cell cycle.[1]

Where it came from and why

The authors concluded that changing both the nonleaving and the leaving group was important for finding better antitumour platinum complexes. Later reviews describe DACH platinum complexes as circumventing some forms of acquired cisplatin resistance in preclinical models.

Cancers

  • Advanced colorectal cancer

    The 2002 label covered use with infusional 5-FU/LV after first-line bolus 5-FU/LV and irinotecan.[1]

  • Stage III colon cancer (adjuvant)

    A November 2004 letter approved adjuvant use with infusional 5-FU/LV after complete resection, based on improved disease-free survival with no demonstrated overall survival benefit at a median follow-up of 4 years.[6]

Family and partners

Derived from: Cisplatin

Worth knowing

  • A 2001 review states that around 3,000 cisplatin analogues had been synthesised over the previous 30 years, and that oxaliplatin was the only DACH platinum to enter clinical development and reach marketing approval.[4]
  • The original 2002 US label said approval was based on response rate and an interim analysis showing improved time to radiographic progression, and that no results yet showed a clinical benefit such as symptom improvement or survival.[1]
  • An FDA letter of January 2004 states that the application was approved under the accelerated-approval regulations (21 CFR 314 Subpart H) and that approval of the first-line combination use fulfilled one of its commitments.[5]
  • A 1993 review reported that DACH compounds, including oxaliplatin, were the only series then in clinical trial on the basis of circumventing acquired cisplatin resistance in some, mainly murine, preclinical models.[3]
  • A 2026 review says oxaliplatin entered the market in Europe and the United States in the late 1990s and early 2000s and describes it as the first platinum drug indicated for colorectal cancer.[7]

On this site

References

  1. U.S. Food and Drug Administration. Eloxatin (oxaliplatin for injection): label revised 9 August 2002 (NDA 021492, original approval). Source
  2. Kidani Y, Inagaki K, Iigo M, Hoshi A, Kuretani K. Antitumor activity of 1,2-diaminocyclohexane--platinum complexes against sarcoma-180 ascites form. J Med Chem. 1978;21(12):1315-8. PubMedDOI
  3. Kelland LR. New platinum antitumor complexes. Crit Rev Oncol Hematol. 1993;15(3):191-219. PubMedDOI
  4. Laadem A, Cvitkovic E. [Oxaliplatin: a first DACH-platinum in oncology]. Bull Cancer. 2001;88 Spec No:S9-13. PubMed
  5. U.S. Food and Drug Administration. Approval letter, NDA 21-492/S-002, Eloxatin (oxaliplatin for injection), signed 9 January 2004. Source
  6. U.S. Food and Drug Administration. Approval letter, NDA 21-492/S-004 and S-005, Eloxatin (oxaliplatin for injection), signed 4 November 2004. Source
  7. Kamusheva MS, Varbanov HP. Current clinical applications and future developments of platinum-based anticancer drugs. J Biol Inorg Chem. 2026;31(6):469-488. PubMedDOI