A multicenter phase II study of XRP6258 administered as a 1-h i.v. infusion every 3 weeks in taxane-resistant metastatic breast cancer patients.
BACKGROUND
XRP6258 is a novel taxoid with a low affinity for P-glycoprotein. This multicenter phase II study assessed the activity of XRP6258 in the treatment of taxane-resistant metastatic breast cancer (MBC).


METHODS
XRP6258 was administered as a 1-h i.v. infusion every 3 weeks at 20 mg/m(2) (then, in the absence of severe toxicity, at 25 mg/m(2) from cycle 2). The primary end point was the objective response rate (ORR) assessed according to response evaluation criteria in solid tumours (RECIST) guidelines.


RESULTS
Seventy-one patients were enrolled. The median relative dose intensity was 0.98. The ORR was 14% (two complete, eight partial responses). Eighteen patients (25%) had stable disease of >3 months duration. At a median follow-up of 20.0 months, the median time to progression was 2.7 months, and the median overall survival 12.3 months. The most common grade 3/4 adverse events (AEs) were neutropenia (73%) and leucopenia (55%), with a low febrile neutropenia rate (3%) and infrequent grade 3/4, treatment-related, non-hematological AEs (<5% patients for any AE). Two deaths were reported, one related to study drug and one to unknown cause.


CONCLUSIONS
XRP6258 was active and well tolerated in this group of MBC patients with taxane-resistant disease. These results support the further clinical development of this agent.
Pivot
X
X
Department of Medical Oncology, University Hospital Jean Minjoz, Institut National de la Santé et de la Recherche Médicale, Unit 645, Besançon, France. Xavier.pivot@univ-fcomte.fr
Koralewski
P
P
Hidalgo
J L
JL
Chan
A
A
Gonçalves
A
A
Schwartsmann
G
G
Assadourian
S
S
Lotz
J P
JP
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000556:secondary*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D018570:Risk Assessment; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage* / Q000494:pharmacology; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D043823:Taxoids; C532412:XRP6258; C080625:taxane