Rational indication for docetaxel rechallenge in metastatic castration-resistant prostate cancer.
Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Docetaxel rechallenge has shown preserved anti-tumour activity and has therefore been proposed as an option for further treatment in patients with metastatic castration-resistant prostate cancer, who have shown a good response to first-line chemotherapy with docetaxel. The present study provides evidence of docetaxel activity in patients who were treated with full-dose (75 mg/m(2) ) 3-weekly docetaxel at first-line chemotherapy and rechallenge. It shows that PSA response to first-line chemotherapy may provide a rational indication for docetaxel rechallenge.


OBJECTIVE
•  To determine whether prostate-specific antigen (PSA) response at first-line chemotherapy with docetaxel correlates with PSA response and survival at docetaxel rechallenge in patients with metastatic castration-resistant prostate cancer (mCRPC).


METHODS
•  We retrospectively evaluated the oncological outcomes of patients with mCRPC, who were treated with full-dose (75 mg/m(2) ), 3-weekly docetaxel plus prednisone/prednisolone at first-line chemotherapy and rechallenge, between 1999 and 2011, at our institution. •  The endpoints were PSA-progression-free survival (PSA-PFS) and overall survival (OS) at docetaxel rechallenge. •  Statistical analyses included Kaplan-Meier curves and log-rank tests to evaluate the effect of PSA response at first-line chemotherapy on PSA-PFS and OS at rechallenge.


RESULTS
•  Fourty-four patients were included in the analysis. •  At a median (range) follow-up of 26.4 (9.8-89.8) months after the first administration of docetaxel, 24 (55%) patients had died. At first-line chemotherapy, 36 (82%) patients achieved a reduction in PSA level of ≥50%. At rechallenge, 10 (28%) patients responded with a reduction of ≥50% for a second time. •  The median (95% confidence interval [CI]) PSA-PFS was 5.9 (95% CI 3.5-6.8) months and the median OS was 21.8 (95% CI 19.9-23.7) months at docetaxel rechallenge. •  Of the PSA response variables evaluated, only a PSA level reduction of ≥50% at first-line chemotherapy correlated significantly with prolonged PSA-PFS (5.8 vs. 4.5 months; P= 0.01) and OS (22.1 vs. 7.2 months; P= 0.03) at rechallenge.


CONCLUSIONS
•  In the present single-institution study, a reduction in PSA level of ≥50% at first-line chemotherapy with docetaxel correlated with superior PSA-PFS and OS in the rechallenge setting and might, therefore, present a rational indication for docetaxel rechallenge.
Department of Urology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. m.heck@lrz.tum.de
Matthias M
MM
Heck
Mark
M
Thalgott
Margitta
M
Retz
Petra
P
Wolf
Tobias
T
Maurer
Roman
R
Nawroth
Georgios
G
Hatzichristodoulou
Jürgen E
JE
Gschwend
Hubert
H
Kübler
D000230:Adenocarcinoma / Q000097:blood / Q000556:secondary / Q000628:therapy*; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D018450:Disease Progression; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009919:Orchiectomy; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000556:secondary / Q000628:therapy*; D011838:Radiation-Sensitizing Agents; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D043823:Taxoids; D000077143:Docetaxel; D017430:Prostate-Specific Antigen