Oxaliplatin colorectal cancer

Oxaliplatin (Eloxatin ) is similar to other platinum analogs (e.g., cisplatin) in that it binds to the N-7 position of guanine, which results in cross-linking of DNA and double-stranded DNA breaks.26,40 Oxaliplatin differs from cisplatin in that the DNA damage induced by oxaliplatin may not be as easily recognized by DNA repair genes often seen in colorectal cancer. Oxaliplatin, in combination with 5-FU-based regimens, is indicated for the first- and second-line treatment of metastatic colon cancer, as well as the adjuvant treatment of colon cancer. 

Oxaliplatin is a newer platinum-based agent. It is most frequently administered in combination with fluorouracil and leucovorin for the treatment of colorectal cancer. Oxaliplatin has less ototoxicity and nephrotoxicity than cisplatin and carboplatin. 

Goldberg RM, Sargent DJ, Morton RF, et al. A randomized, controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 2004 22 23-30. 

The second criteria, a different activity spectrum, is met by oxaliplatin (Figure 1.9A), the l isomer of [oxalatol f ra/rv-1,2-diaminocyclohexane)platinum (II)], oxaliplatin, [Pt(II)(oxalato)(DACH)]. This platinum agent is used for secondary treatment of metastatic colorectal cancer.77 Oxaliplatin, like carboplatin, has a kinetically slower leaving group, and is also less nephrotoxic than cisDDP. The limiting toxicity of oxaliplatin is peripheral sensory neuropathy, also seen with cisDDP. The neuropathy affects the extremities and increases in incidence and... 

Oxaliplatin (trans-L-diaminocyclohexane oxalate platinum II) was selected for development based on preclinical antitumor activity in murine leukemia lines and in colon cancer models (151,152). The clinical development of oxaliplatin has been primarily in colorectal cancer alone and in combination with 5-fluorouracil. 

Oxaliplatin is a novel platinum compound that has shown promising activity in colorectal cancers. It has been associated with up to 60% response rates when used as front-line therapy, and 25-50% response rates in relapsed or refractory colorectal cancer. It is currently being evaluated in a Phase I study with 5-FU and radiation in patients with locally advanced esophageal cancer (NCI T99-0061). 

Levi F, Zidani R, Misset JL. Randomized multicentre trial of chronotherapy with oxaliplatin, fluorouracil, and folinic acid in metastatic colorectal cancer. Lancet 1997 350 681-686. 

Cetuximab has modest activity in relapsed colorectal cancer as a single agent but is more effective with irinotecan and possibly oxaliplatin based regimens where a doubling of the response rate has been observed. There is some evidence that cetuximab may reverse irinotecan resistance. Toxic effects of cetuximab include hypersensitivity reactions, malaise, nausea, headache and an acneiform rash. 

Colorectal cancer (CRC) is the third most common cause of cancer-related death in women and men in the United States. The current therapeutic options for patients with metastatic CRC (mCRC) are 5-fluorouracil (5-FU) based chemotherapy regimens with the addition of irinotecan (CPT-11) or oxaliplatin. It still remains a challenge for oncologists to evaluate the reasons for a wide variation in response and toxicity among patients undergoing systemic 5-FU based chemotherapy. Pharmacogenomics... 

Jemal A, Siegel R, Ward E et al. Cancer statistics, 2006. CA Cancer J Clin 2006 56 106-130. de Gramont A, Figer A, Seymour M et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 2000 18 2938-2947. 

Simpson D, Dunn C, Curran M et al. Oxaliplatin a review of its use in eombination therapy for advaneed metastatic colorectal cancer. Drugs 2003 63 2127-2156. 

Shirota Y, StoeWmacher J, Brabender J et al. ERCCl and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy. JC/m Onco/2001 19 4298 304. 

Oxaliplatin Same as cisplatin Colorectal cancer, gastroesophageal cancer, pancreatic cancer Nausea and vomiting, laryngopharyngeal dysesthesias Myelosuppression, peripheral sensory neuropathy, diarrhea... 

Li L, Ahmed B, Mehta K, Kurzrock R. 2007a. Liposomal curcumin with and without oxaliplatin Effects on cell growth, apoptosis, and angiogenesis in colorectal cancer. Mol Cancer Ther 6 1276-1282. 

Drug(s) Oxaliplatin Primary Antineoplastic Indication(s) Colorectal cancer Common Adverse Effects Blood disorders (anemia, leukopenia, neutropenia, thrombocytopenia) joint pain, chest pain... 

Oxaliplatin is a third generation diaminocyclohexane platinum analog. Its mechanism of action is identical to that of cisplatin and carboplatin. However, it is not cross-resistant to cancer cells that are resistant to cisplatin or carboplatin on the basis of mismatch repair defects. This agent was recently approved for use as second-line therapy in metastatic colorectal cancer following treatment with the combination of fluorouracil-leucovorin and irinotecan, and it is now widely used as first-line therapy of this disease as well. Neurotoxicity is dose-limiting and characterized by a peripheral sensory neuropathy, often triggered or worsened upon exposure to cold. While this neurotoxicity is cumulative, it tends to be reversible—in contrast to cisplatin-induced neurotoxicity. 

Levi, F., Zidani, R., Vannetzel, J.M., Per-point, B., Focan, C., Faggiuolo, R., Chollet, P., Garufi, C., Itzhaki, M., Dogliotti L. Chronomodulated versus fixed-infusion-rate delivery of ambulatory chemotherapy with oxaliplatin, fluorouracil, and folinic acid (leucovorin) in patients with colorectal cancer metastases a randomized multi-institutional trial. J. Natl Cancer Inst. 1994, 86 1608-1617. 

The clinical tumor spectrum for oxaliplatin is not yet fully characterized, but oxaliplatin is considered to be the most effective agent beside 5-fluorouracil (5-FU) and irinotecan against colorectal cancer. It also shows a promising activity in breast cancer, which is only marginally sensitive to the conventional Pt compounds. Oxa-... 

Wiseman LR, Adkins JC, Plosker GL, et al. Oxaliplatin. A review of its use in the management of metastatic colorectal cancer. Drugs Aging, 1999, 14, 459-475. 

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