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


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.
Rosati
M S
MS
Department of Oncology A, Policlinico Umberto, Sapienza University of Rome, 155 V.le del Policlinico, 00161 Rome, Italy. sofiarosati@tiscali.it
Raimondi
C
C
Baciarello
G
G
Grassi
P
P
Giovannoni
S
S
Petrelli
E
E
Basile
M L
ML
Girolami
M
M
Di Seri
M
M
Frati
L
L
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D043823:Taxoids; D004317:Doxorubicin