Oxaliplatin

Molecular formula C8Hi4N204Pt Molecular weight 397.29 CAS Registry No 61825-94-3 Merck Index 13, 6981 

Sample preparation Filter (Sartorius Centrisart 110 000 MW cut-offi while centrifuging at 4000 g at 4° for 1 h, inject an aliquot of the ultrafiltrate. 

Mobile phase MeOH 250 mM pH 7.0 succinic acid buffer 90 10 Flow rate 0.5 Injection volume 25 

Detector UV 344 following post-column reaction. The column effluent mixed with 2.7 mM sodium N, IV-diethyldithiocarbamate in MeOH pumped at 0.17 mL/min and the mixture flowed through a 2.3 m long 0.51 mm ID length of FIFE tubing to the detector. A 2 m length of the tubing was heated in a microwave field (ca. 130 W, Smithcreator, Personal Chemistry, Sweden) at about 110°. 

Ehrsson, H. Wallin, I. Liquid chromatographic determination of oxaliplatin in blood using post-column derivatization in a microwave field followed by photometric detection, J.Chromatogr.B, 2003, 795, 291-294. 

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Oxaliplatin belongs to the group of diaminocyclohex-ane platinum complexes that can overcome platinum resistance. Its place in the primary and adjuvant treatment of colon cancets is being defined. It is prominently neurotoxic. 

Other subgroups of alkylating agents are the nitrosoureas (examples carmustine, BCNU lomustine, CCNXJ) and the triazenes (example dacarbazine, DTIC). Platinum derivatives (cisplatin, carboplatin, oxaliplatin) have an action that is analogous to that of alkylating agents (formation of crosslinks) and therefore are appended to this class, as well. 

C KjPt 10025-99-7) see Cisplatin Oxaliplatin potassium thiocyanate see under potassium rhodanide prajmalium bromide... 

Flurouracil-based chemotherapy is the standard regimen used in adjuvant treatment of colon cancer. It is usually given for 6 months with leucovorin, and based on recent clinical trials, oxaliplatin also may be added to the combination. 

Triple -drug therapy consisting of 5-fluorouracil and leucovorin with oxaliplatin or irinotecan improves survival compared with 5-fluorouracil plus leucovorin alone and is... 

FOLFOX4 Day 1 Oxaliplatin 85 mg/m2 IV + leucovorin 200 mg/m2 IV, followed by 5-fluorouracil 400 mg/m2 IV bolus and then 5-fluorouracil 600 mg/m2 IV over 22 hours Day 2 Leucovorin 200 mg/m2, followed by 5-fluorouracil 400 mg/m2 IV bolus and then 5-fluorouracil 600 mg/m2 IV over 22 hours Repeat every 2 weeks... 

CAPOX Capecitabine 1 000 mg/m2 twice a day orally for 14 days Oxaliplatin 130 mg/m2 IV on day 1 Repeat every 3 weeks... 

FOLFOX Folinic acid (leucovorin) + 5-fluorouracil + oxaliplatin given as combined IV boluses and continuous infusions... 

CAPOX Capecitabine + Oxaliplatin given as oral therapy and IV boluses... 

Capecitabine is an oral prodrug of 5-FU that also is effective in the adjuvant setting and is being evaluated as a replacement for 5-FU for patient convenience and safety reasons. Data suggest that capecitabine is at least equivalent to 5-FU and leucovorin in efficacy and is better tolerated by patients.24 Consequently, most practitioners feel that capecitabine is an acceptable alternative to IV 5-FU plus leucovorin. However, the role of capecitabine with additional chemotherapy agents such as oxaliplatin requires further study... 

Oxaliplatin Similar to other platinum analogs Dose-limiting... 

The dose of capecitabine begins at 1250 mg/m2 twice a day when used by itself lower doses are used often when it is given in combination with irinotecan or oxaliplatin or in patients with renal insufficiency. The dose should be taken on a full stomach with breakfast and dinner. Capecitabine administered with warfarin can result in significant increases in the patient s INR and requires close monitoring to prevent bleeding. The convenience of oral administration and an improvement in toxicity make capecitabine a useful alternative to IV 5-FU both by itself and incorporated into other regimens used in colon 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. 

Laboratory monitoring is performed before initiating therapy and before each cycle of chemotherapy. A complete blood count should be obtained prior to each course of chemotherapy to ensure that hematologic values are adequate. In particular, white blood cell counts and absolute neutrophil counts can be decreased in patients receiving chemotherapy such as irinote-can and 5-FU and increase the risk of infection. Baseline liver function tests and an assessment of renal function should be done prior to and periodically during therapy. Other selected laboratory tests include checking for the presence of protein in the urine in patients receiving oxaliplatin and bevacizumab. 

Andre T, Boni C, Mounedji-Boudiaf L, et al. Oxaliplatin, fluo-rouracil, leucovorin as adjuvant treatment for colon cancer. New Engl J Med 2004 350 2243-2351. 

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 main uses for platinum are as a catalyst in the catalytic converter and in fuel cells. And of course platinum, a very expensive metal, is used in jewellery. However, certain platinum-containing compounds are chemotherapeutic agents, examples being cisplatin, carboplatin and oxaliplatin. This explains the synthetic interest in platinum compounds. 

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