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Why give Taxol (Paxel) before carboplatin?

Medically reviewed by Carmen Fookes, BPharm. Last updated on Oct 12, 2021.

Official answer

by Drugs.com

Taxol (paclitaxel, Paxel) must be given before carboplatin because if carboplatin is given before Taxol, it stops Taxol from having an effect on cancer cells. This is called a scheduling interaction because when Taxol is given before carboplatin, there is little interaction and both agents work as intended.

The combination of carboplatin and paclitaxel is widely used to treat multiple solid tumors including ovarian, lung, and breast cancer. Research has shown that the pretreatment or simultaneous treatment with carboplatin inhibited Taxol-induced I-kappa, B-alpha degradation, and BCL-2 phosphorylation. Further analyses demonstrated that carboplatin could significantly interfere with the cytotoxic effects of Taxol on both mitotic arrest and apoptotic cell death unless Taxol was administered before carboplatin. These results indicate that the interaction between paclitaxel and carboplatin is highly schedule-dependent and the optimal schedule is Taxol (paclitaxel, Paxel) followed by carboplatin.

Why is Taxol and carboplatin used together?

A landmark study in 1996 showed that Taxol and carboplatin in combination was better for the treatment of advanced ovarian cancer because it was less toxic than the combination used at the time, Taxol and cisplatin. Carboplatin-Taxol in combination were also just as effective as cisplatin-Taxol. Carboplatin-Taxol have been a standard chemotherapy combination used for more than 25 years for the treatment of ovarian cancer. The combination is also used to treat many other solid tumors.

How effective is Taxol and carboplatin?

The combination of carboplatin-Taxol is well tolerated and achieves a clinical response rate of 50% to 81% and an average progression free survival (PFS) of 13.6 to 19.3 months. Other findings include:

  • For patients with optimally debulked advanced ovarian cancer revealed the median PFS for carboplatin-Taxol was 20.7 months compared to 19.4 with cisplatin-Taxol
  • Overall survival was 57.4 months with carboplatin-Taxol compared to 48.7 months with cisplatin-Taxol
  • Gastrointestinal, renal, metabolic toxicity and leukopenia were significantly more in cisplatin-Taxol group compared with carboplatin-Taxol
  • Quality-of-life scores at the end of treatment were significantly better with carboplatin-Taxol (65.25) compared with cisplatin-Taxol (51.97).
  • Toxic side effects, such as nausea and weight loss, are less with carboplatin-Taxol
  • Carboplatin-Taxol can be administered safely and effectively over a 3-hour infusion period. Previously, cisplatin-Taxol was administered over 24 hours, requiring a hospital stay.
References
  • Taxol (paclitaxel) Updated 04/2021. E.R. Squibb & Sons, L.L.C. https://www.drugs.com/pro/taxol.html
  • Xiong X, Sui M, Fan W, Kraft AS. Cell cycle-dependent antagonistic interactions between paclitaxel and carboplatin in combination therapy. Cancer Biol Ther. 2007 Jul;6(7):1067-73. doi: 10.4161/cbt.6.7.4323. PMID: 17568189.

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