Anthracycline rechallenge using pegylated liposomal doxorubicin in patients with metastatic breast cancer: a pooled analysis using individual data from four prospective trials.
BACKGROUND
The aim of this study was to determine the activity of anthracycline rechallenge using pegylated liposomal doxorubicin (PLD) in patients with metastatic breast cancer (MBC) previously treated with conventional anthracyclines.


METHODS
Pooled individual data from four prospective trials were used, and the primary end point of the pooled analysis was clinical benefit rate (CBR). The studies comprised 935 patients, of whom 274 had received PLD in the metastatic setting after prior exposure to conventional anthracyclines (rechallenge population).


RESULTS
The majority of patients were heavily pretreated. Previous anthracycline therapy was administered in the adjuvant (14%) or metastatic setting (46%), or both (40%). The overall CBR from rechallenge with PLD was 37.2% (95% CI, 32.4-42.0). In univariate analyses, the CBR was significantly higher in patients with less exposure to prior chemotherapy, in taxane-naive patients, and in patients with a favourable Eastern Cooperative Group performance status of 0 vs 1 vs 2 (53.3 vs 35.5 vs 18.2%; P<0.001). In multivariate analyses, performance status proved to be the only independent predictor of the CBR achieved with PLD rechallenge (P=0.038). There was no statistically significant difference in CBR regarding the setting, cumulative dose of and/or resistance to prior anthracyclines, or time since prior anthracycline administration.


CONCLUSIONS
Anthracycline rechallenge using PLD is effective in patients with MBC who have a favourable performance status, regardless of setting, resistance, cumulative dose or time since prior conventional anthracycline therapy.
Klinik für Onkologie und Hämatologie am Krankenhaus Nordwest, Krankenhaus Nordwest, Steinbacher Hohl 2-26, 60488 Frankfurt am Main, Germany. albatran@aol.com
S-E
SE
Al-Batran
M
M
Güntner
C
C
Pauligk
M
M
Scholz
R
R
Chen
B
B
Beiss
S
S
Stopatschinskaja
W
W
Lerbs
N
N
Harbeck
E
E
Jäger
D000293:Adolescent; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002986:Clinical Trials as Topic; D018450:Disease Progression; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009362:Neoplasm Metastasis; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011446:Prospective Studies; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077235:Vinorelbine; D055815:Young Adult
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D016685:Mitomycin; D014747:Vinblastine; D004317:Doxorubicin; D000077235:Vinorelbine