Evaluation of epothilone B analog in advanced soft tissue sarcoma: a phase II study of the phase II consortium.
OBJECTIVE
Epothilones are a new class of nontaxane tubulin polymerization agents that have activity in taxane-resistant tumors. Epothilone B (BMS-247550) is a semisynthetic analog of the natural product epothilone B. This study was performed to determine the activity of BMS-247550 in patients with soft tissue sarcomas (STSs) who had not received prior chemotherapy for metastatic disease.


METHODS
Patients with measurable, advanced, or metastatic STS with no prior chemotherapy for metastatic disease were treated with BMS-2457550 50 mg/m(2) intravenously during 1 hour every 21 days. All responses were confirmed 4 weeks later.


RESULTS
Thirty-one patients (median age, 54 years; range, 19 to 78 years; 48% female) were entered onto the trial and were assessable for response. All but one patient had an Eastern Cooperative Oncology Group performance score of 0% or 1%, and 39% had received prior adjuvant chemotherapy. Mean follow-up was 22 months, with a confirmed response rate of 6% (95% CI, 0% to 17%). Median time to progression was 4.5 months (95% CI, 1.9 to 8.3 months), and 1 year progression-free survival was 17% (95% CI, 8% to 38%). Median survival was 16.4 months, with a 1-year survival of 61% (95% CI, 46% to 81%). Toxicity was mainly hematologic, with eight of 31 (26%) patients experiencing grade 3 to 4 leukopenia; 15 of 31 patients (48%) experienced grade 3 to 4 neutropenia. The grade 3 to 4 nonhematologic toxicities included neuropathies (26%), myalgia (13%), and fatigue (10%).


CONCLUSIONS
BMS-247550 has limited activity against STSs when given in this dose and schedule. The clinical toxicity is similar to that of taxanes.
Okuno
Scott
S
Mayo Clinic College of Medicine, 200 First St, Southwest, Medical Oncology, Rochester, MN 55905, USA. okuno.scott@mayo.edu
Maples
William J
WJ
Mahoney
Michelle R
MR
Fitch
Tom
T
Stewart
James
J
Fracasso
Paula M
PM
Kraut
Michael
M
Ettinger
David S
DS
Dawkins
Fitzroy
F
Erlichman
Charles
C
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D034261:Epothilones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D012509:Sarcoma / Q000188:drug therapy*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D034261:Epothilones; C093788:epothilone B