An open-label phase 2 study of twice-weekly bortezomib and intermittent pegylated liposomal doxorubicin in patients with ovarian cancer failing platinum-containing regimens

Gabriella Parma, Rosanna Mancari, Gianluca Del Conte, Giovanni Scambia, Angiolo Gadducci, Dagmar Hess, Dionyssios Katsaros, Cristiana Sessa, Andrea Rinaldi, Francesco Bertoni, Andrea Vitali, Carlo Vittorio Catapano, Silvia Marsoni, Helgi Van De Velde, Nicoletta Colombo

Research output: Contribution to journalArticle

Abstract

Background: Pegylated liposomal doxorubicin (PLD) is an established treatment for relapsed ovarian cancer. Preclinical and clinical evidences in other tumor types suggest that the proteasome inhibitor bortezomib can act synergistically with PLD. Methods: Patients with relapsed ovarian cancer (N = 58), previously treated with platinum (100%) and taxane (95%), received bortezomib, 1.3 mg/m 2 intravenous (days 1, 4, 8, and 11), and PLD, 30 mg/m 2 intravenous (day 1), every 3 weeks. Tumor responses were assessed using Response Evaluation Criteria In Solid Tumors and Gynecologic Cancer Intergroup criteria. An optimal 2-stage design was implemented. Gene expression profiling in peripheral blood was characterized before and during treatment in 10 platinum-sensitive patients enrolled in stage 2 of the study. Results: Median number of bortezomib-PLD cycles was 3.5. Of 38 patients in the platinumsensitive group, 9 responses were observed (median duration, 4.8 months). The platinumresistant group was closed at stage 1 owing to lack of response. Toxicity was moderate and mainly consisted of hematologic, gastrointestinal, and mucositis events. Of the total 58 patients, peripheral neuropathy was reported in 9 patients (none were grade 3). Transcription profiling identified the prevalence of genes associated with ribonucleoprotein complexes, RNA processing, and protein translation. The gene expression changes were more robust in patients who responded or had stable disease compared with patients who had progressive disease. Conclusions: The combination of bortezomib and PLD was well tolerated, but the antitumor activity is insufficient to warrant further investigation in ovarian cancer.

Original languageEnglish
Pages (from-to)792-800
Number of pages9
JournalInternational Journal of Gynecological Cancer
Volume22
Issue number5
DOIs
Publication statusPublished - Jun 2012

Fingerprint

Platinum
Ovarian Neoplasms
Neoplasms
Mucositis
Proteasome Inhibitors
Ribonucleoproteins
Protein Biosynthesis
Gene Expression Profiling
Peripheral Nervous System Diseases
liposomal doxorubicin
Bortezomib
RNA
Gene Expression
Therapeutics
Genes

Keywords

  • Bortezomib
  • Ovarian cancer
  • Pegylated liposomal doxorubicin
  • Proteasome inhibitor

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Oncology

Cite this

An open-label phase 2 study of twice-weekly bortezomib and intermittent pegylated liposomal doxorubicin in patients with ovarian cancer failing platinum-containing regimens. / Parma, Gabriella; Mancari, Rosanna; Del Conte, Gianluca; Scambia, Giovanni; Gadducci, Angiolo; Hess, Dagmar; Katsaros, Dionyssios; Sessa, Cristiana; Rinaldi, Andrea; Bertoni, Francesco; Vitali, Andrea; Catapano, Carlo Vittorio; Marsoni, Silvia; Van De Velde, Helgi; Colombo, Nicoletta.

In: International Journal of Gynecological Cancer, Vol. 22, No. 5, 06.2012, p. 792-800.

Research output: Contribution to journalArticle

Parma, Gabriella ; Mancari, Rosanna ; Del Conte, Gianluca ; Scambia, Giovanni ; Gadducci, Angiolo ; Hess, Dagmar ; Katsaros, Dionyssios ; Sessa, Cristiana ; Rinaldi, Andrea ; Bertoni, Francesco ; Vitali, Andrea ; Catapano, Carlo Vittorio ; Marsoni, Silvia ; Van De Velde, Helgi ; Colombo, Nicoletta. / An open-label phase 2 study of twice-weekly bortezomib and intermittent pegylated liposomal doxorubicin in patients with ovarian cancer failing platinum-containing regimens. In: International Journal of Gynecological Cancer. 2012 ; Vol. 22, No. 5. pp. 792-800.
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AU - Parma, Gabriella

AU - Mancari, Rosanna

AU - Del Conte, Gianluca

AU - Scambia, Giovanni

AU - Gadducci, Angiolo

AU - Hess, Dagmar

AU - Katsaros, Dionyssios

AU - Sessa, Cristiana

AU - Rinaldi, Andrea

AU - Bertoni, Francesco

AU - Vitali, Andrea

AU - Catapano, Carlo Vittorio

AU - Marsoni, Silvia

AU - Van De Velde, Helgi

AU - Colombo, Nicoletta

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N2 - Background: Pegylated liposomal doxorubicin (PLD) is an established treatment for relapsed ovarian cancer. Preclinical and clinical evidences in other tumor types suggest that the proteasome inhibitor bortezomib can act synergistically with PLD. Methods: Patients with relapsed ovarian cancer (N = 58), previously treated with platinum (100%) and taxane (95%), received bortezomib, 1.3 mg/m 2 intravenous (days 1, 4, 8, and 11), and PLD, 30 mg/m 2 intravenous (day 1), every 3 weeks. Tumor responses were assessed using Response Evaluation Criteria In Solid Tumors and Gynecologic Cancer Intergroup criteria. An optimal 2-stage design was implemented. Gene expression profiling in peripheral blood was characterized before and during treatment in 10 platinum-sensitive patients enrolled in stage 2 of the study. Results: Median number of bortezomib-PLD cycles was 3.5. Of 38 patients in the platinumsensitive group, 9 responses were observed (median duration, 4.8 months). The platinumresistant group was closed at stage 1 owing to lack of response. Toxicity was moderate and mainly consisted of hematologic, gastrointestinal, and mucositis events. Of the total 58 patients, peripheral neuropathy was reported in 9 patients (none were grade 3). Transcription profiling identified the prevalence of genes associated with ribonucleoprotein complexes, RNA processing, and protein translation. The gene expression changes were more robust in patients who responded or had stable disease compared with patients who had progressive disease. Conclusions: The combination of bortezomib and PLD was well tolerated, but the antitumor activity is insufficient to warrant further investigation in ovarian cancer.

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