Phase II trial of non-pegylated liposomal doxorubicin and low-dose prednisone in second-line chemotherapy for hormone-refractory prostate cancer

Marco Montanari, Francesco Fabbri, Ermanno Rondini, Giovanni Luca Frassineti, Rodolfo Mattioli, Silvia Carloni, Emanuela Scarpi, Wainer Zoli, Dino Amadori, Giorgio Cruciani

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Aims and background. Non-pegylated liposomal doxorubicin (NPLD) (Myocet) has shown marked in vitro activity in castration-resistant prostate cancer (CRPC) and also in docetaxel-resistant cells, higher than that shown by pegylated liposomal doxorubicin. Its activity would seem to be due to a high intracellular drug concentration and induction of Golgi-dependent apoptosis. On the basis of these results, a clinical study was designed to assess the activity of NPLD and low-dose prednisone in second-line therapy. Methods. Fifty-four patients were enrolled and evaluated. Eligibility criteria were histologically confirmed CRPC, PSA >20 ng/mL or measurable lesions according to the RECIST criteria, previous docetaxel-based chemotherapy, and adequate cardiac function. Patients were treated with weekly intravenous NPLD 25 mg/m2 and daily prednisone 10 mg until progression. Results. Median patient age was 69 years (range, 52-83) and median baseline PSA concentration was 120 ng/mL (range, 5.35-4350). Sixteen (29.6%) patients had measurable lesions. Objective or PSA responses (>50% reduction) were observed in 8 (14.8%) patients. The median time to progression was 2.8 months and the median overall survival was 11.3 months. Toxicity was generally mild (grade 1-2) and infrequent, with grade 3-4 neutropenia in 12.9% of cases. Grade 3 nonhematological toxicities included nausea in 2 patients (3.7%) and fatigue and stomatitis in 1 case (1.9%). No drug-related serious adverse events were reported. Conclusions. Weekly administration of NPLD is a well tolerated treatment with proven albeit limited activity.

Original languageEnglish
Pages (from-to)696-701
Number of pages6
JournalTumori
Volume98
Issue number6
DOIs
Publication statusPublished - Nov 2012

Fingerprint

Prednisone
Prostatic Neoplasms
docetaxel
Hormones
Drug Therapy
Castration
Stomatitis
Neutropenia
Pharmaceutical Preparations
Doxorubicin
Nausea
Fatigue
liposomal doxorubicin
Apoptosis
Survival
Therapeutics

Keywords

  • Castration-resistant prostate cancer
  • Chemotherapy
  • Liposomal anthracyclines
  • Translational research

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase II trial of non-pegylated liposomal doxorubicin and low-dose prednisone in second-line chemotherapy for hormone-refractory prostate cancer. / Montanari, Marco; Fabbri, Francesco; Rondini, Ermanno; Frassineti, Giovanni Luca; Mattioli, Rodolfo; Carloni, Silvia; Scarpi, Emanuela; Zoli, Wainer; Amadori, Dino; Cruciani, Giorgio.

In: Tumori, Vol. 98, No. 6, 11.2012, p. 696-701.

Research output: Contribution to journalArticle

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abstract = "Aims and background. Non-pegylated liposomal doxorubicin (NPLD) (Myocet) has shown marked in vitro activity in castration-resistant prostate cancer (CRPC) and also in docetaxel-resistant cells, higher than that shown by pegylated liposomal doxorubicin. Its activity would seem to be due to a high intracellular drug concentration and induction of Golgi-dependent apoptosis. On the basis of these results, a clinical study was designed to assess the activity of NPLD and low-dose prednisone in second-line therapy. Methods. Fifty-four patients were enrolled and evaluated. Eligibility criteria were histologically confirmed CRPC, PSA >20 ng/mL or measurable lesions according to the RECIST criteria, previous docetaxel-based chemotherapy, and adequate cardiac function. Patients were treated with weekly intravenous NPLD 25 mg/m2 and daily prednisone 10 mg until progression. Results. Median patient age was 69 years (range, 52-83) and median baseline PSA concentration was 120 ng/mL (range, 5.35-4350). Sixteen (29.6{\%}) patients had measurable lesions. Objective or PSA responses (>50{\%} reduction) were observed in 8 (14.8{\%}) patients. The median time to progression was 2.8 months and the median overall survival was 11.3 months. Toxicity was generally mild (grade 1-2) and infrequent, with grade 3-4 neutropenia in 12.9{\%} of cases. Grade 3 nonhematological toxicities included nausea in 2 patients (3.7{\%}) and fatigue and stomatitis in 1 case (1.9{\%}). No drug-related serious adverse events were reported. Conclusions. Weekly administration of NPLD is a well tolerated treatment with proven albeit limited activity.",
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T1 - Phase II trial of non-pegylated liposomal doxorubicin and low-dose prednisone in second-line chemotherapy for hormone-refractory prostate cancer

AU - Montanari, Marco

AU - Fabbri, Francesco

AU - Rondini, Ermanno

AU - Frassineti, Giovanni Luca

AU - Mattioli, Rodolfo

AU - Carloni, Silvia

AU - Scarpi, Emanuela

AU - Zoli, Wainer

AU - Amadori, Dino

AU - Cruciani, Giorgio

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KW - Translational research

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