Weekly combination of non-pegylated liposomal doxorubicin and taxane in first-line breast cancer: wALT trial (phase I–II) — Ann Oncol

Weekly combination of non-pegylated liposomal doxorubicin and taxane in first-line breast cancer: wALT trial (phase I–II)
M. S. Rosati1,*, C. Raimondi1, G. Baciarello1, P. Grassi1, S. Giovannoni1, E. Petrelli1, M. L. Basile1, M. Girolami2, M. Di Seri1 and L. Frati1

Ann Oncol (2011) 22 (2): 315-320.
doi: 10.1093/annonc/mdq392
First published online: August 6, 2010

+ Author Affiliations
1Department of Oncology A
2IV Surgical Division, Policlinico “Umberto I”, “Sapienza” University of Rome, Rome, Italy


*Correspondence to: Dr M. S. Rosati, Department of Oncology A, Policlinico “Umberto I”, “Sapienza” University of Rome, 155 V.le del Policlinico, 00161 Rome, Italy. Tel: +39-06-4441675; Fax: +39-06-4941035; E-mail: sofiarosati@tiscali.it


Received March 11, 2010.
Revision received May 25, 2010.
Accepted June 1, 2010.


Abstract
Background: Through different pharmacodynamic–kinetic interactions, weekly administration of proved efficacy agents can overcome resistance with lower toxicity and greater benefit. Based on this assumption, we designed a phase I–II trial with weekly non-pegylated liposomal anthracycline and taxane in first-line breast cancer patients.

Patients and methods: We enrolled 56 previously untreated metastatic breast cancer patients; they were randomly assigned to receive paclitaxel (Taxol) (50 mg/mq) or docetaxel (Taxotere) (30 mg/mq) combined with non-pegylated liposomal anthracycline (25 mg/mq) on days 1, 8 and 15 every 4 weeks. The primary end points were the clinical benefit and treatment-related toxic effects assessment. Secondary end points were time-to-disease progression (TTP) and overall survival (OS).

Results: The overall clinical benefit was 87.04%. World Health Organization G3–4 toxic effects included neutropenia (45%), anemia (44%), complete alopecia (83%), severe onycholysis and neuropathy. The 24% of patients developed left ventricular ejection fraction reduction but none >10% with recover after treatment completion. The median absolute decrease from baseline was 1%. Median TTP was 11 months and median OS was 23 months.

Conclusions: Combined weekly administration of taxane and non-pegylated liposomal anthracycline is well tolerated and clinical benefit data encourage phase III study design.

Weekly combination of non-pegylated liposomal doxorubicin and taxane in first-line breast cancer: wALT trial (phase I–II) — Ann Oncol