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01-04-2014 | Original Article

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)

Authors: Filippos Koinis, Aristidis Polyzos, Athina Christopoulou, Zafeiris Zafeiriou, Christos Emmanouilidis, Elisavet Papadimitraki, Antonia Kalykaki, Kostas Kalbakis, George Samonis, Vassilis Georgoulias

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2014

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.

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 PubMedCrossRef

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

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 PubMedCentralPubMedCrossRef

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):389–393PubMed

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):195–208PubMedCentralPubMedCrossRef

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):2099–2106PubMedCrossRef

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 PubMedCentralPubMedCrossRef

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

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

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):444–450PubMedCrossRef

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):121–124PubMedCrossRef

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 PubMedCrossRef

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):130–135PubMedCrossRef

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):2167–2170PubMedCrossRef

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):2733–2739PubMed

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 PubMedCentralPubMedCrossRef

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 PubMedCrossRef

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 PubMedCentralPubMedCrossRef

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):3312–3322PubMed

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 PubMedCrossRef

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 PubMedCentralPubMedCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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):610–618PubMedCrossRef

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 PubMedCrossRef

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 CrossRef

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):1521–1526PubMed

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 PubMedCrossRef

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 PubMedCrossRef

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

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):1094–1099PubMedCrossRef

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 PubMedCrossRef

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 PubMedCentralPubMedCrossRef

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 PubMedCrossRef

Title: 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)
Authors: Filippos Koinis
Aristidis Polyzos
Athina Christopoulou
Zafeiris Zafeiriou
Christos Emmanouilidis
Elisavet Papadimitraki
Antonia Kalykaki
Kostas Kalbakis
George Samonis
Vassilis Georgoulias
Publication date: 01-04-2014
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 4/2014
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-014-2411-2

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