Triptorelin 6-month formulation in the management of patients with locally advanced and metastatic prostate cancer: an open-label, non-comparative, multicentre, phase III study.
OBJECTIVE
Triptorelin 6-month formulation was developed to offer greater convenience to both patients and physicians by reducing the injection frequency. The efficacy, pharmacokinetics and safety of a new 6-month formulation of triptorelin were investigated over 12 months (48 weeks). The primary objective was to evaluate the formulation in achieving castrate serum testosterone levels (< or = 1.735 nmol/L or < or = 50 ng/dL) on day 29 and in maintaining castration at months 2-12. Absence of luteinizing hormone (LH) stimulation and change in prostate-specific antigen (PSA) level were also assessed.


METHODS
An open-label, non-comparative, phase III study in 120 patients with advanced prostate cancer was conducted from July 2006 to August 2007 in private and public institutions in South Africa. Each patient received two consecutive intramuscular injections of triptorelin embonate (pamoate) 22.5 mg at an interval of 24 weeks. In all patients, testosterone (primary outcome measurement) was measured at baseline and then every 4 weeks; LH was measured before and 2 hours after the two injections. PSA was measured on day 1 and at weeks 12, 24, 36 and 48. Adverse events were recorded at each visit.


RESULTS
In the intent-to-treat population, 97.5% (95% CI 92.9, 99.5) of patients achieved castrate serum testosterone levels by day 29, and 93.0% (95% CI 86.8, 97.0) maintained castration at months 2-12. After the second injection, 98.3% of patients showed absence of LH stimulation. The most frequent drug-related adverse events were hot flushes (71.7% of patients). No patient withdrew from the study as a result of an adverse event.


CONCLUSIONS
The triptorelin 6-month formulation was well tolerated and was able to achieve and maintain castration for the treatment of locally advanced and metastatic prostate cancer. By reducing the frequency of required injections, this new formulation offers a more convenient treatment regimen. (Clinical Trial Registration,NCT00751790 at www.clinicaltrials.gov).
Lundström
Eija A
EA
Debiopharm SA, Lausanne, Switzerland. elundstrom@debiopharm.com
Rencken
Rupert K
RK
van Wyk
Johann H
JH
Coetzee
Lance J E
LJ
Bahlmann
Johann C M
JC
Reif
Simon
S
Strasheim
Erdam A
EA
Bigalke
Martin C
MC
Pontin
Alan R
AR
Goedhals
Louis
L
Steyn
Douw G
DG
Heyns
Chris F
CF
Aldera
Luigi A
LA
Mackenzie
Thomas M
TM
Purcea
Daniela
D
Grosgurin
Pierre Y
PY
Porchet
Hervé C
HC
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D019584:Hot Flashes / Q000139:chemically induced; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013019:South Africa; D013739:Testosterone / Q000097:blood*; D017329:Triptorelin Pamoate / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
D018931:Antineoplastic Agents, Hormonal; D003692:Delayed-Action Preparations; D017329:Triptorelin Pamoate; D013739:Testosterone; D017430:Prostate-Specific Antigen