Randomised phase II/III study of docetaxel with or without risedronate in patients with metastatic Castration Resistant Prostate Cancer (CRPC), the Netherlands Prostate Study (NePro).
BACKGROUND
This multicentre, randomised, open label, phase II/III study aimed to investigate the potential benefit of adding risedronate (R) to docetaxel (D) in patients with metastatic Castration Resistant Prostate Cancer (CRPC).


METHODS
CRPC patients with bone metastasis were randomly assigned to receive D 75 mg/m(2) every 3 weeks and prednisone as first line chemotherapy, with or without R 30 mg oral once daily. The primary end-point was time to progression (TTP). A composite end-point of objective progression by RECIST criteria, PSA progression, or pain progression, whichever occurred first, was applied. The study had 80% power to detect an improvement of 30% in median TTP in the DR group (two-sided α=0.05).


RESULTS
Five hundred and ninety-two men (301 D versus 291 DR) were randomised. TTP was 7.4 [D] versus 6.5 [DR] months (p=0.75). PSA and pain response rates were similar, 66.3% [D] versus 65.9% [DR] and 27.9% [D] versus 31.2% [DR], respectively. Median overall survival (OS) was 18.4 [D] versus 19.2 [DR] months (p=0.33). There were no differences in toxicity.


CONCLUSIONS
The addition of the third generation bisphosphonate, risedronate, in the setting of effective first line docetaxel based chemotherapy did not increase efficacy, as indicated by the lack of improvement in TTP, OS, PSA- and pain response.
Department of Medical Oncology, Erasmus University Medical Center, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands. h.meulenbeld@erasmusmc.nl
H J
HJ
Meulenbeld
E D
ED
van Werkhoven
J L L M
JL
Coenen
G J
GJ
Creemers
O J L
OJ
Loosveld
P C
PC
de Jong
A J
AJ
Ten Tije
S D
SD
Fosså
M
M
Polee
W
W
Gerritsen
O
O
Dalesio
R
R
de Wit
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D002369:Castration; D018450:Disease Progression; D000077143:Docetaxel; D012968:Etidronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D009664:Norway; D010146:Pain / Q000517:prevention & control; D011241:Prednisone / Q000008:administration & dosage; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000068296:Risedronic Acid; D018570:Risk Assessment; D012307:Risk Factors; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
D000726:Androgen Antagonists; D000972:Antineoplastic Agents, Phytogenic; D050071:Bone Density Conservation Agents; D043823:Taxoids; D000077143:Docetaxel; D017430:Prostate-Specific Antigen; D000068296:Risedronic Acid; D012968:Etidronic Acid; D011241:Prednisone