Phase II multicenter study of larotaxel (XRP9881), a novel taxoid, in patients with metastatic breast cancer who previously received taxane-based therapy.
BACKGROUND
Treatment options are limited for patients with refractory metastatic breast cancer (MBC). Larotaxel (XRP9881) is a novel taxoid with preclinical activity against taxane-resistant breast cancer. The current phase II trial of larotaxel was conducted in women with taxane-treated MBC.


METHODS
Patients were stratified by response to prior taxane therapy (resistant or nonresistant). Larotaxel 90 mg/m(2) was administered as a 1-h infusion every 3 weeks. Patients were evaluated for tumor response every two cycles. A blinded external response review committee determined the overall response rate (ORR), duration of response (DOR), and time to progression (TtP) of the disease. Median survival time (MST) and safety were also evaluated.


RESULTS
One hundred and thirty patients were treated. In the nonresistant group, the ORR was 42%; median DOR 5.3 months; median TtP 5.4 months; and MST 22.6 months. In the resistant group, the ORR was 19%; median DOR 5.0 months; median TtP 1.6 months; and MST 9.8 months. The most common grade 3/4 adverse events were neutropenia (82%), fatigue (15%), diarrhea (12%), febrile neutropenia (9%), neutropenic infection (8%), and sensory neuropathy (7%).


CONCLUSIONS
Larotaxel has good activity, manageable toxicity, and a favorable therapeutic index in women with taxane-pretreated MBC.
Diéras
V
V
Department of Medical Oncology, Institut Curie, Paris, France. Electronic address: veronique.dieras@curie.net.
Limentani
S
S
Carolinas Hematology-Oncology Associates, Charlotte, NC, USA.
Romieu
G
G
Centre Val d'Aurelle, Montpellier.
Tubiana-Hulin
M
M
Centre René Huguenin, Saint Cloud.
Lortholary
A
A
Centre Catherine de Sienne, Nantes, France.
Kaufman
P
P
Hematology/Oncology, Dartmouth/Hitchcock Medical Center, Lebanon, NH, USA.
Girre
V
V
Department of Medical Oncology, Institut Curie, Paris, France.
Besenval
M
M
Sanofi-aventis, Bagneux, France.
Valero
V
V
MD Anderson Cancer Center, Houston, TX, USA.
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000008:administration & dosage*; D015331:Cohort Studies; D003967:Diarrhea / Q000139:chemically induced; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced; D011446:Prospective Studies; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D043823:Taxoids; C080625:taxane; C531079:larotaxel