Brief Article
Copyright ©2012 Baishideng. All rights reserved.
World J Obstet Gynecol. Oct 10, 2012; 1(3): 35-39
Published online Oct 10, 2012. doi: 10.5317/wjog.v1.i3.35
Platinum-resistant ovarian cancer: Prematurely stopped phase II Austrian AGO chemotherapy studies
Edgar Petru, Birgit Volgger, Gerhard Bogner, Lukas Angleitner-Boubenizek, Martina Deibl, Christian Schauer, Alexander Reinthaller, Gerhard Wolfram, Alain Gustave Zeimet, Christian Marth
Edgar Petru, Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria
Birgit Volgger, Christian Marth, Department of Obstetrics and Gynecology, Medical University of Innsbruck, and AGO-Studienzentrale, 6020 Innsbruck, Austria
Gerhard Bogner, Department of Obstetrics and Gynecology, Klinikum Wels, 4600 Wels, Austria
Lukas Angleitner-Boubenizek, Department of Gynecology, Hospital Barmherzige Schwestern, 4020 Linz, Austria
Martina Deibl, Institute of Biostatistics, University of Innsbruck, 6020 Innsbruck, Austria
Christian Schauer, Department of Gynecology, Hospital Barmherzige Brüder Graz, 8020 Graz, Austria
Alexander Reinthaller, Department of Obstetrics and Gynecology, Medical University of Vienna, 1090 Vienna, Austria
Gerhard Wolfram, Department of Gynecology, Hospital Barmherzige Schwestern, 4910 Ried, Austria
Alain Gustave Zeimet, Department of Obstetrics and Gynecology, Medical University of Innsbruck, 6020 Innsbruck, Austria
Author contributions: Petru E, Marth C and Volgger B made substantial contributions to the conception and design, acquisition of data, analysis and interpretation of data; all authors drafted the article and revised it critically for important intellectual content; and all authors have given final approval of the version to be published.
Correspondence to: Edgar Petru, MD, Professor, Department of Obstetrics and Gynecology, Medical University of Graz, Auenbruggerplatz 14, A-8036 Graz, Austria. edgar.petru@medunigraz.at
Telephone: +43-316-38581082 Fax: +43-316-38512546
Received: April 6, 2012
Revised: July 9, 2012
Accepted: September 12, 2012
Published online: October 10, 2012
Abstract

AIM: To report the results of two phase II studies of chemotherapy in patients with platinum-resistant and platinum-refractory ovarian cancer and discuss the current status of systemic therapy in this disease.

METHODS: Two subsequent Austrian Arbeitsgemeinschaft für Gynäkologische Onkologie (AGO) phase II studies have been carried out. Patients either had platinum-refractory or platinum-resistant disease, i.e., disease progression during first line platinum-based therapy or recurrence within 6 mo following the last platinum-containing chemotherapy, respectively. In the first study, 6 cycles of irinotecan at 55 mg/m2 and docetaxel 25 mg/m2 were both administered on days 1, 8 and 15 of a 4 wk cycle. In the second phase II study, either non-pegylated (PEG) liposomal doxorubicin (L-DXR) 60 mg/m2 monotherapy on day 1 and PEG filgrastim on day 2 (arm A) or L-DXR at 50 mg/m2 and gemcitabine (GEM) at 650 mg/m2 on day 1 and GEM on day 8 (arm B) were administered every 4 wk. Patients in arm B received prophylactic filgrastim 5 μg/kg per day from days 3 to 6 and from days 9 to 12, respectively.

RESULTS: Response rates in studies were 14% and 17%, respectively. The progression-free survival was less than 3 mo. Diarrhea was most prevalent in patients treated with irinotecan + docetaxel, while stomatitis/mucositis occurred in a quarter of patients treated with L-DXR +/- GEM + granulocyte colony stimulating factor, respectively. Following treatment with the latter regimen, a total of 11 serious adverse events were recorded among the 12 patients included. The rate of remissions of the regimens used in these two Austrian AGO studies was low and their toxicity significant. Due to their low therapeutic index, neither of these regimens can be recommended in this heavily pretreated patient population with platinum-resistant ovarian cancer exhibiting a high tumor-associated symptom burden.

CONCLUSION: The two reported phase II studies of the Austrian AGO in platinum-resistant disease had to be terminated prematurely due to a low therapeutic index. Treatment of this disease remains a clinical dilemma. Bevacizumab seems to be active at this late-stage disease but may be associated with significant bowel toxicity.

Keywords: Platinum-resistance; Ovarian cancer; Chemotherapy; Gemcitabine; Non-pegylated liposomal doxorubicin; Irinotecan; Docetaxel