Skip to main content

Chemotherapy time interval and development of platinum and taxane resistance in ovarian, fallopian, and peritoneal carcinomas

Abstract

Objective

To evaluate drug resistance after exposure to neoadjuvant chemotherapy and to postoperative chemotherapy in epithelial ovarian, fallopian, and primary peritoneal carcinomas.

Methods

In vitro drug resistance assay results (EDR Assay, Oncotech, Inc.) for platinum and taxane were evaluated for the following three groups: (1) primary cytoreductive surgery without prior chemotherapy; (2) primary cytoreductive surgery after neoadjuvant chemotherapy with platinum and taxane; and (3) recurrent cases after postoperative chemotherapy with platinum and taxane. Proportions of extreme drug resistance (EDR) were analyzed with Fisher’s exact test.

Results

There were 277 cases that underwent primary cytoreductive surgery without prior chemotherapy: 14 cases of primary cytoreductive surgery after neoadjuvant chemotherapy with platinum and taxane, and 65 recurrent cases. Primary cytoreductive cases following neoadjuvant chemotherapy displayed an increased proportion of EDR to platinum agents compared to primary cytoreductive surgery without prior chemotherapy: neoadjuvant versus non-neoadjuvant, cisplatin 30 versus 7.3%, OR 5.4, 95%CI 1.3–23.2, P = 0.027; carboplatin 33.3 versus 9.2%, OR 4.9, 95%CI 1.4–17.6, P = 0.038. There were no differences in the proportion of EDR to taxanes between the two groups. On the contrary, recurrent cases showed an increased proportion of EDR to paclitaxel compared to primary cytoreductive surgery without prior chemotherapy: recurrent versus primary, paclitaxel 33.3 versus 21.1%, OR 1.9, 95%CI 1.0–3.5, P = 0.031. There were no differences in the proportion of EDR for platinum and docetaxel between the two groups. Among recurrent cases, there was statistical significance between proportion of paclitaxel EDR and time interval of initial and recurrent surgeries (R 2 0.143, P = 0.011). Recurrent surgery after 5 years from initial cytoreduction was significantly associated with increased proportion of EDR to paclitaxel: 61.5 versus 22.6%, OR 5.5, 95%CI 1.35–22.2, P = 0.011.

Conclusions

Platinum resistance was common after neoadjuvant chemotherapy, while paclitaxel resistance was common after postoperative chemotherapy.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2

References

  1. Jemal A, Siegel R, Ward E et al (2008) Cancer statistics, 2008. CA Cancer J Clin 58:71–96. doi:10.3322/CA.2007.0010

    Article  PubMed  Google Scholar 

  2. Heintz AP, Odicino F, Maisonneuve P et al (2003) Carcinoma of the ovary. Int J Gynaecol Obstet 83S:135–166. doi:10.1016/S0020-7292(03)90118-4

    Article  Google Scholar 

  3. McGuire WP, Hoskins WJ, Brady MF et al (1996) Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med 334:1–6. doi:10.1056/NEJM199601043340101

    Article  CAS  PubMed  Google Scholar 

  4. Modesitt SC, Jazaeri AA (2007) Recurrent epithelial ovarian cancer: pharmacotherapy and novel therapeutics. Expert Opin Pharmacother 8:2293–2305. doi:10.1517/14656566.8.14.2293

    Article  CAS  PubMed  Google Scholar 

  5. EDR Assay®, http://www.oncotech.com. Cited 1 October 2008

  6. Kern DH, Weisenthal LM (1990) Highly specific prediction of antineoplastic drug resistance with an in vitro assay using suprapharmacologic drug exposures. J Natl Cancer Inst 82:582–588. doi:10.1093/jnci/82.7.582

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest statement

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Koji Matsuo.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Matsuo, K., Eno, M.L., Im, D.D. et al. Chemotherapy time interval and development of platinum and taxane resistance in ovarian, fallopian, and peritoneal carcinomas. Arch Gynecol Obstet 281, 325 (2010). https://doi.org/10.1007/s00404-009-1121-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00404-009-1121-1

Keywords

  • Platinum resistance
  • Taxane resistance
  • Neoadjuvant chemotherapy
  • Ovarian cancer