Primary drug resistance/sensitivity in vitro and clininical outcome in ovarian cancer patients
Authors:
I. Sedláková 1; J. Tošner 1; M. Červinka 2; K. Brigulová 2; A. Řezáč 1; J. Špaček 1; J. Laco 3; P. Škapinec 1
Authors‘ workplace:
Porodnická a gynekologická klinika LF UK a Fakultní nemocnice Hradec Králové, přednosta doc. MUDr. J. Tošner, CSc.
1; Ústav biologie a lékařské genetiky, Lékařská fakulta Hradec Králové UK v Praze, přednosta prof. MUDr. RNDr. M. Červinka, CSc.
2; Fingerlandův ústav patologie Fakultní nemocnice Hradec Králové, přednosta prof. MUDr. A. Ryška, PhD.
3
Published in:
Ceska Gynekol 2011; 76(3): 184-189
Overview
Objective:
To assay correlation between primary resistance/sensitivity in vitro by MTT test in solid tumor and ascitic fluid and clininical outcome in ovarian cancer patients.
Design:
Prospective study.
Setting:
Department of Gynecology and Obstetrics, Medical Faculty Charles University, Prague and University Hospital, Hradec Králové.
Methods:
MTT – (3-(4,5 – Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) chemosensitivity assay was performed in 45 samples of ovarian cancer tissue and 26 samples of ascitic fluid in ovarian cancer patients. We studied the in vitro drug resistance profiles of ovarian cancer specimens exposed to cisplatin, carboplatin, paclitaxel, topotecan, gemcitabin, etoposid.
Results:
The highest incidence of primary drug resistance in vitro had gemcitabin and carboplatin and the lowest incidence of primary drug resistance had cisplatin and topotecan. Cisplatin had lower incidence of primary drug resistance in vitro than carboplatin. Grade and stage of epithelial ovarian cancer did not correlate to the primary drug resistance/sensitivity in vitro in ovarian cancer patients. The histological subtype of epithelial ovarian cancer correlated to the resistance and sensitivity to chemotherapeutic agents in vitro. Ovarian cancer patients with primary drug resistance to paclitaxel and carboplatin in vitro had more complications during primary chemotherapy, shorter progression free interval and worse prognosis of the disease.
Conclusion:
The lowest incidence of primary drug resistance in vitro had cisplatin. Ovarian cancer patients with in vitro resistance to paclitaxel and carboplatin had significantly higher risk for progression of disease when treated with standard platinum-paclitaxel based regimens. The primary resistance/sensitivity assay would contribute to the targeted treatment and better prognosis of ovarian cancer patients.
Key words:
ovarian cancer, resistance, sensitivity, chemotherapeutic agent, MTT assay, targeted treatment.
Sources
1. Cibula, D., Petruželka, L., a kol. Onkogynekologie. Praha: Grada Publishing, 2009, 508 s.
2. Cloven, NG., Kyshtoobayeva, A., Burger, AR., et al. In vitro chemoresistance and biomarker profiles are unique for histologic subtypes of epithelial ovarian cancer. Gynecol Oncol, 2004, 92, p. 160-166.
3. Cortazar, P., Johnson, BE. Review of the efficacy of individualized chemotherapy selected by in vitro drug senzitivity testing for patients with cancer. J Clin Oncol, 1999, 17, p. 1625-1631.
4. Cwiertka, K., Hajduch, M., Pilka, R., et al. Chemoterapie ovariálního karcinomu s ohledem na stanovení in vitro chemosenzitivity – vybrané kasuistiky. Klin Onkol, 2000, 13, s. 58-59.
5. Fruehauf, PJ., Alberts, DS. In vitro drug resistance versus chemosenzitivity: two sides of different coins. J Clin Oncol, 2005, 23, p. 3641-3643.
6. Freuhauf, JP., Maneta, A. Use of the extreme drug resistance assay to evaluate mechanisms of resistance in ovarian cancer: taxol resistance and MDR-1 expression. Contrib Gynaecol Obstet, 1994, 19, p. 39-52.
7. Holloway, RW., Mehta, RS., Finkler, NJ., et al. Association between in vitro platinum resistance in the EDR assay and clinical outcomes for ovarian cancer patients. Gynecol Oncol, 2002, 87, p. 8-16.
8. Chumchalová, J., Kovařík, J. Metodiky testování chemosenzitivity/chemorezistence nádorů in vitro. Klin Onkol, 2000, 13, s. 18-21.
9. Michalová, E., Poprach, A., Němečková, I., et al. Predikce citlivosti nádorových buněk k chemoterapeutikům ex vivo – úskalí a limitace vlastní metody. Klin Onkol, 2008, 21, s. 93-97.
10. Muggia, FM., Braly, PS., Brady, MF., et al. Phase III randomized study of cisplatin versus paclitaxel in patients with suboptimal stage III or IV ovarian cancer. A Gynecologic Oncology Group study. J Clin Oncol, 2000, 18, p. 106-115.
11. Nosková, V., Hajduch, M., Mihál, V., Cwiertka, K. Mechanismy mnohočetné lékové rezistence a jejich význam pro klinickou praxi I. typická MDR. Klin Onkol, 2000, 13, s. 4-9.
12. Ozols, FR. Paclitaxel (Taxol)/Carboplatin combination chemotherapy in the treatment of advanced ovarian cancer. Seminars in Oncology, 2000, 3, s. 3-7.
13. Sedláková, I., Tošner, J., Řezáč, A., et al. Rezistence/senzitivita in vitro u pacientek s karcinomem ovaria. Čes Gynek, 2010, 75, s. 186-191.
14. Talač, R., Žaloudík, J., Hajdúch, M., et al. Hodnocení lékové rezistence in vitro a její klinické implikace. Klin Onkol, 2000, 13, s. 2-3.
15. Tewari, SK., Mehta, SR., Burger, AR., et al. Conservation of in vitro drug resistance patterns in epithelial ovarian carcinoma. Gynecol Oncol, 2005, 98, s. 360-368.
16. The ICON Group: Paclitaxel plus carboplatin versus standard chemotherapy with either single agent carboplatin or cyclophosphamide, doxorubicin and cisplatin in women with ovarian cancer. Lancet, 2002, 360, p. 505-515.
17. Tošner, J., Červinka, M., Sedláková, I., et al. Testování účinnosti cytostatik s využitím zmražených buněk karcinomu ovaria. Slov Gynek Porod, 2010, 17, s. 121-124.
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Paediatric gynaecology Gynaecology and obstetrics Reproduction medicineArticle was published in
Czech Gynaecology
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