Skip to main content

Advertisement

Log in

Salvage chemotherapy with docetaxel and pegylated liposomal doxorubicin in pretreated patients with platinum- and taxane-sensitive ovarian cancer: a multicenter phase II trial of the Hellenic Oncology Research Group (HORG)

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

To evaluate the safety and antitumor activity of docetaxel (DOC) and pegylated liposomal doxorubicin (PLD) combination in patients with platinum- and taxane-sensitive ovarian cancer.

Patients and methods

Twenty-three patients were enrolled. DOC was administered at the dose of 40 mg/m2 intravenously (i.v.) and PLD at 20 mg/m2 i.v. on days 1 and 15 in cycles of 28 days. The study was closed prematurely due to slow accrual.

Results

Seven (30.4 %) patients achieved objective response (three complete, four partial), while five (21.7 %) others experienced stable disease (overall disease control rate 52.1 %). The median progression-free survival was 4.8 months and the median overall survival 18.8 months. Grade 3–4 neutropenia occurred in two (8.7 %) and one (4.3 %) patients, respectively. Febrile neutropenia occurred in two patients. The most common non-hematological grade 3 toxicity was hand-foot syndrome (13 % of patients). There was no treatment-related death.

Conclusions

The combination of pegylated liposomal doxorubicin and docetaxel is a well tolerated and a relatively active regimen in pretreated patients with platinum- and taxane-sensitive advanced ovarian cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90. doi:10.3322/caac.20107

    Article  PubMed  Google Scholar 

  2. SEER Stat Fact Sheets: Ovary Cancer (2013) http://seer.cancer.gov/statfacts/html/ovary.html

  3. Elit L, Hirte H (2013) Palliative systemic therapy for women with recurrent epithelial ovarian cancer: current options. Onco Targets Ther 6:107–118. doi:10.2147/OTT.S30238

    Article  PubMed Central  PubMed  Google Scholar 

  4. Markman M, Rothman R, Hakes T, Reichman B, Hoskins W, Rubin S, Jones W, Almadrones L, Lewis JL Jr (1991) Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin. J Clin Oncol 9(3):389–393

    PubMed  CAS  Google Scholar 

  5. Fung-Kee-Fung M, Oliver T, Elit L, Oza A, Hirte HW, Bryson P (2007) Optimal chemotherapy treatment for women with recurrent ovarian cancer. Curr Oncol 14(5):195–208

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  6. Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB, Wheeler S, Swart AM, Qian W, Torri V, Floriani I, Jayson G, Lamont A, Trope C (2003) Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet 361(9375):2099–2106

    Article  PubMed  CAS  Google Scholar 

  7. Pignata S, De Placido S, Biamonte R, Scambia G, Di Vagno G, Colucci G, Febbraro A, Marinaccio M, Lombardi AV, Manzione L, Carteni G, Nardi M, Danese S, Valerio MR, de Matteis A, Massidda B, Gasparini G, Di Maio M, Pisano C, Perrone F (2006) Residual neurotoxicity in ovarian cancer patients in clinical remission after first-line chemotherapy with carboplatin and paclitaxel: the Multicenter Italian Trial in Ovarian cancer (MITO-4) retrospective study. BMC Cancer 6:5. doi:10.1186/1471-2407-6-5

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  8. Bookman MA (1999) Extending the platinum-free interval in recurrent ovarian cancer: the role of topotecan in second-line chemotherapy. Oncologist 4(10337378):87–94

    PubMed  CAS  Google Scholar 

  9. Engblom P, Rantanen V, Kulmala J, Heiskanen J, Grenman S (1997) Taxane sensitivity of ovarian carcinoma in vitro. Anticancer Res 17(4A):2475–2479

    PubMed  CAS  Google Scholar 

  10. Kelland LR, Abel G (1992) Comparative in vitro cytotoxicity of taxol and Taxotere against cisplatin-sensitive and -resistant human ovarian carcinoma cell lines. Cancer Chemother Pharmacol 30(6):444–450

    Article  PubMed  CAS  Google Scholar 

  11. Hanauske AR, Degen D, Hilsenbeck SG, Bissery MC, Von Hoff DD (1992) Effects of Taxotere and taxol on in vitro colony formation of freshly explanted human tumor cells. Anticancer Drugs 3(2):121–124

    Article  PubMed  CAS  Google Scholar 

  12. Vasey PA, Jayson GC, Gordon A, Gabra H, Coleman R, Atkinson R, Parkin D, Paul J, Hay A, Kaye SB (2004) Phase III randomized trial of docetaxel–carboplatin versus paclitaxel–carboplatin as first-line chemotherapy for ovarian carcinoma. J Natl Cancer Inst 96(22):1682–1691. doi:10.1093/jnci/djh323

    Article  PubMed  CAS  Google Scholar 

  13. Rose PG, Blessing JA, Ball HG, Hoffman J, Warshal D, DeGeest K, Moore DH (2003) A phase II study of docetaxel in paclitaxel-resistant ovarian and peritoneal carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 88(2):130–135

    Article  PubMed  CAS  Google Scholar 

  14. Kaye SB, Piccart M, Aapro M, Francis P, Kavanagh J (1997) Phase II trials of docetaxel (Taxotere) in advanced ovarian cancer—an updated overview. Eur J Cancer 33(13):2167–2170

    Article  PubMed  CAS  Google Scholar 

  15. Verschraegen CF, Sittisomwong T, Kudelka AP, Guedes E, Steger M, Nelson-Taylor T, Vincent M, Rogers R, Atkinson EN, Kavanagh JJ (2000) Docetaxel for patients with paclitaxel-resistant Mullerian carcinoma. J Clin Oncol 18(14):2733–2739

    PubMed  CAS  Google Scholar 

  16. Pisano C, Cecere SC, Di Napoli M, Cavaliere C, Tambaro R, Facchini G, Scaffa C, Losito S, Pizzolorusso A, Pignata S (2013) Clinical trials with pegylated liposomal doxorubicin in the treatment of ovarian cancer. J Drug deliv 2013:898146. doi:10.1155/2013/898146

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  17. Pignata S, Scambia G, Ferrandina G, Savarese A, Sorio R, Breda E, Gebbia V, Musso P, Frigerio L, Del Medico P, Lombardi AV, Febbraro A, Scollo P, Ferro A, Tamberi S, Brandes A, Ravaioli A, Valerio MR, Aitini E, Natale D, Scaltriti L, Greggi S, Pisano C, Lorusso D, Salutari V, Legge F, Di Maio M, Morabito A, Gallo C, Perrone F (2011) Carboplatin plus paclitaxel versus carboplatin plus pegylated liposomal doxorubicin as first-line treatment for patients with ovarian cancer: the MITO-2 randomized phase III trial. J Clin Oncol 29(27):3628–3635. doi:10.1200/JCO.2010.33.8566

    Article  PubMed  CAS  Google Scholar 

  18. Wagner U, Marth C, Largillier R, Kaern J, Brown C, Heywood M, Bonaventura T, Vergote I, Piccirillo MC, Fossati R, Gebski V, Lauraine EP (2012) Final overall survival results of phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients. Br J Cancer 107(4):588–591. doi:10.1038/bjc.2012.307

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  19. Gordon AN, Fleagle JT, Guthrie D, Parkin DE, Gore ME, Lacave AJ (2001) Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol 19(14):3312–3322

    PubMed  CAS  Google Scholar 

  20. O’Byrne KJ, Bliss P, Graham JD et al (2002) A phase III study of doxil/caylex versus paclitaxel in platinum treated taxane naive relapsed ovarian cancer. J Clin Oncol 21, abstract 808, ASCO annual meeting

  21. Fracasso PM, Rodriguez LC, Herzog TJ, Fears CL, Goodner SA, Govindan R, Picus J, Rader JS, Tan BR, Arquette MA (2003) Phase I dose and sequencing study of pegylated liposomal doxorubicin and docetaxel in patients with advanced malignancies. Cancer 98(3):610–617. doi:10.1002/cncr.11547

    Article  PubMed  CAS  Google Scholar 

  22. Cancer Therapy Evaluation Program (1999) National Cancer Institute. http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcv20_4-30-992.pdf

  23. D’Agostino G, Ferrandina G, Ludovisi M, Testa A, Lorusso D, Gbaguidi N, Breda E, Mancuso S, Scambia G (2003) Phase II study of liposomal doxorubicin and gemcitabine in the salvage treatment of ovarian cancer. Br J Cancer 89(7):1180–1184. doi:10.1038/sj.bjc.6601284

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  24. Ferrandina G, Paris I, Ludovisi M, D’Agostino G, Testa A, Lorusso D, Zanghi M, Pisconti S, Pezzella G, Adamo V, Breda E, Scambia G (2005) Gemcitabine and liposomal doxorubicin in the salvage treatment of ovarian cancer: updated results and long-term survival. Gynecol Oncol 98(2):267–273. doi:10.1016/j.ygyno.2005.04.018

    Article  PubMed  CAS  Google Scholar 

  25. Katsaros D, Oletti MV, Rigault de la Longrais IA, Ferrero A, Celano A, Fracchioli S, Donadio M, Passera R, Cattel L, Bumma C (2005) Clinical and pharmacokinetic phase II study of pegylated liposomal doxorubicin and vinorelbine in heavily pretreated recurrent ovarian carcinoma. Ann Oncol 16(2):300–306. doi:10.1093/annonc/mdi055

    Article  PubMed  CAS  Google Scholar 

  26. Verhaar-Langereis M, Karakus A, van Eijkeren M, Voest E, Witteveen E (2006) Phase II study of the combination of pegylated liposomal doxorubicin and topotecan in platinum-resistant ovarian cancer. Int J Gynecol Cancer 16(1):65–70. doi:10.1111/j.1525-1438.2006.00298.x

    Article  PubMed  CAS  Google Scholar 

  27. Joly F, Sevin E, Lortholary A, Priou F, Paitel JF, Fabbro M, Henry-Amar M, Hamond K, Bourgeois H (2010) Association of pegylated liposomal doxorubicin and ifosfamide in early recurrent ovarian cancer patients: a multicenter phase II trial. Gynecol Oncol 116(3):312–316. doi:10.1016/j.ygyno.2009.09.036

    Article  PubMed  CAS  Google Scholar 

  28. Campos SM, Matulonis UA, Penson RT, Lee H, Berkowitz RS, Duska LR, Fuller AF Jr, Wilson KS, Puchalski TA, Supko JG, Seiden MV (2003) Phase II study of liposomal doxorubicin and weekly paclitaxel for recurrent Mullerian tumors. Gynecol Oncol 90(3):610–618

    Article  PubMed  CAS  Google Scholar 

  29. Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, Muggia FM, Pujade-Lauraine E, Lisyanskaya AS, Makhson AN, Rolski J, Gorbounova VA, Ghatage P, Bidzinski M, Shen K, Ngan HY, Vergote IB, Nam JH, Park YC, Lebedinsky CA, Poveda AM (2010) Trabectedin plus pegylated liposomal Doxorubicin in recurrent ovarian cancer. J Clin Oncol 28(19):3107–3114. doi:10.1200/JCO.2009.25.4037

    Article  PubMed  CAS  Google Scholar 

  30. Garcia AA, Yessaian A, Pham H, Facio G, Muderspach L, Roman L (2012) Phase II study of gemcitabine and docetaxel in recurrent platinum resistant ovarian cancer. Cancer Investig 30(4):295–299. doi:10.3109/07357907.2012.657812

    Article  CAS  Google Scholar 

  31. Itani Y, Hosokawa K, Ito K, Takeuchi S, Tabata T, Tsubamoto H, Fujita H, Akiyama M, Adachi S (2009) A phase I/II study of docetaxel and gemcitabine combination for chemotherapy-resistant ovarian cancer. Anticancer Res 29(5):1521–1526

    PubMed  CAS  Google Scholar 

  32. Monk BJ, Sill MW, Hanjani P, Edwards R, Rotmensch J, De Geest K, Bonebrake AJ, Walker JL (2011) Docetaxel plus trabectedin appears active in recurrent or persistent ovarian and primary peritoneal cancer after up to three prior regimens: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol 120(3):459–463. doi:10.1016/j.ygyno.2010.11.012

    Article  PubMed  CAS  Google Scholar 

  33. Ferrandina G, Ludovisi M, De Vincenzo R, Salutari V, Lorusso D, Colangelo M, Prantera T, Valerio MR, Scambia G (2007) Docetaxel and oxaliplatin in the second-line treatment of platinum-sensitive recurrent ovarian cancer: a phase II study. Ann Oncol 18(8):1348–1353. doi:10.1093/annonc/mdm136

    Article  PubMed  CAS  Google Scholar 

  34. Wang J, Han N, Wang HL, Zhang ZM, Fan QX (2009) Therapeutic effect of docetaxel combined with oxaliplatin for treatment of recurrent epithelial ovarian cancer. Nan fang yi ke da xue xue bao = J South Med Univ 29(11):2319–2320

    CAS  Google Scholar 

  35. Aravantinos G, Bafaloukos D, Fountzilas G, Christodoulou C, Papadimitriou C, Pavlidis N, Kalofonos HP, Gogas H, Kosmidis P, Dimopoulos MA (2003) Phase II study of docetaxel–vinorelbine in platinum-resistant, paclitaxel-pretreated ovarian cancer. Ann Oncol 14(7):1094–1099

    Article  PubMed  CAS  Google Scholar 

  36. Gupta D, Owers RL, Kim M, Kuo DY, Huang GS, Shahabi S, Goldberg GL, Einstein MH (2009) A phase II study of weekly topotecan and docetaxel in heavily treated patients with recurrent uterine and ovarian cancers. Gynecol Oncol 113(3):327–330. doi:10.1016/j.ygyno.2009.02.018

    Article  PubMed  CAS  Google Scholar 

  37. Coleman RL, Duska LR, Ramirez PT, Heymach JV, Kamat AA, Modesitt SC, Schmeler KM, Iyer RB, Garcia ME, Miller DL, Jackson EF, Ng CS, Kundra V, Jaffe R, Sood AK (2011) Phase 1–2 study of docetaxel plus aflibercept in patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer. Lancet Oncol 12(12):1109–1117. doi:10.1016/S1470-2045(11)70244-3

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  38. Wenham RM, Lapolla J, Lin HY, Apte SM, Lancaster JM, Judson PL, Gonzalez-Bosquet J, Herschberger A, Havrilesky LJ, Secord AA (2013) A phase II trial of docetaxel and bevacizumab in recurrent ovarian cancer within 12 months of prior platinum-based chemotherapy. Gynecol Oncol 130(1):19–24. doi:10.1016/j.ygyno.2013.04.049

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was partially supported by a grant from the Cretan Association for Biomedical Research (CABR).

Conflict of interest

There is no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Vassilis Georgoulias.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Koinis, F., Polyzos, A., Christopoulou, A. et al. Salvage chemotherapy with docetaxel and pegylated liposomal doxorubicin in pretreated patients with platinum- and taxane-sensitive ovarian cancer: a multicenter phase II trial of the Hellenic Oncology Research Group (HORG). Cancer Chemother Pharmacol 73, 819–825 (2014). https://doi.org/10.1007/s00280-014-2411-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-014-2411-2

Keywords

Navigation