A retrospective evaluation of second-line chemotherapy response in hormone-refractory prostate carcinoma: second line taxane-based therapy after first-line epothilone-B analog ixabepilone (BMS-247550) therapy.
BACKGROUND
Epothilones and taxanes interfere with microtubule function. Ixabepilone, which is an epothilone-B analog, has activity against taxane-resistant cell lines and as first-line therapy for men with hormone-refractory prostate carcinoma (HRPC). Clinical cross-resistance of ixabepilone and taxanes in HRPC is unknown.


METHODS
Records were evaluated retrospectively from patients with HRPC who were treated on a randomized Phase II trial of ixabepilone with or without estramustine and who subsequently received taxane chemotherapy. Posttherapy declines in prostate-specific antigen (PSA) levels and time to PSA progression were defined by consensus criteria. The median survival was evaluated by using the Kaplan-Meier method.


RESULTS
Forty-nine patients who received ixabepilone with estramustine (28 patients) or without estramustine (21 patients) subsequently received second-line taxane therapy. Second-line PSA declines > or = 50% were achieved by 51% of patients (95% confidence interval [95% CI], 33-66%). Second-line PSA declines > or = 50% were achieved by 61% of patients (95% CI, 42-78%) who achieved a first-line PSA decline > or = 50% with ixabepilone, compared with 33% of patients (95% CI, 13-59%) who did not (P = 0.08). Patients who discontinued first-line ixabepilone treatment for disease progression were less likely to achieve a PSA decline > or = 50% in response to second-line, taxane-based therapy compared with patients who discontinued for toxicity or patient preference (36% vs. 71%; P = 0.01).


CONCLUSIONS
Second-line taxane chemotherapy after ixabepilone resulted in a substantial frequency of PSA declines. Although patients with ixabepilone-refractory disease were less likely to respond to second-line taxane chemotherapy, 36% did achieve a PSA response. These findings were consistent with incomplete clinical cross-resistance between the taxanes and the epothilones.
Rosenberg
Jonathan E
JE
Division of Hematology/Oncology, University of California-San Francisco, San Francisco, California 94115, USA. jrosenbe@medicine.ucsf.edu
Galsky
Matthew D
MD
Rohs
Nicholas C
NC
Weinberg
Vivian K
VK
Oh
William K
WK
Kelly
W Kevin
WK
Small
Eric J
EJ
D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D034261:Epothilones / Q000008:administration & dosage; D004961:Estramustine / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000401:mortality; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
D001952:Bridged-Ring Compounds; D034261:Epothilones; D043823:Taxoids; C080625:taxane; D004961:Estramustine; D017430:Prostate-Specific Antigen; C430592:ixabepilone