Abstract
Background: Perifosine is an oral alkylphospholipid that inhibits cancer cell growth through decreased Akt phosphorylation. We conducted a phase II trial of perifosine in patients with biochemically recurrent, hormone-sensitive prostate cancer. Patients and Methods: Eligible patients had histologically confirmed prostate cancer, previous prostatectomy and/or radiation therapy, and rising prostate-specific antigen (PSA) without radiographic evidence of metastasis. Previous androgen deprivation therapy < 9 months in duration (completed ≥ 1 year before registration) was allowed. The primary endpoint was PSA response, defined as a decrease by ≥ 50% from the pretreatment value. Treatment was comprosed of a loading dose of perifosine 900 mg orally on day 1, then 100 mg daily starting 24 hours later. Results: Of 25 patients, 24 were evaluable for response. After a median follow-up of 8 months, 5 patients (20%) had a reduction in serum PSA levels, but none met criteria for PSA response. Three patients immediately progressed with no response to therapy. Median progression-free survival was 6.64 months (range, 4.53-12.81 months). No change in the PSA doubling time (7 months) was observed before and after treatment initiation. Dose-limiting toxicities (all grade 3) included hyponatremia, arthritis, hyperuricemia, and photophobia. Conclusion: Although well tolerated, perifosine did not meet prespecified PSA criteria for response as a single agent in biochemically recurrent prostate cancer. However, 20% of patients had evidence of PSA reduction, suggesting modest single-agent clinical activity. The role of perifosine in combination with androgen deprivation or chemotherapy is currently under investigation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 433-437 |
| Number of pages | 5 |
| Journal | Clinical Genitourinary Cancer |
| Volume | 5 |
| Issue number | 7 |
| DOIs | |
| State | Published - Dec 2007 |
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Keywords
- Alkylphospholipids
- Androgen deprivation therapy
- Prostate-specific antigen
ASJC Scopus subject areas
- Oncology
- Urology
Cite this
The AKT inhibitor perifosine in biochemically recurrent prostate cancer : A phase II California/Pittsburgh cancer consortium trial. / Chee, Karen G.; Longmate, Jeff; Quinn, David I.; Chatta, Gurkamal; Pinski, Jacek; Twardowski, Przemyslaw; Pan, Chong-Xian; Cambio, Angelo; Evans, Christopher P; Gandara, David R; Lara, Primo N.
In: Clinical Genitourinary Cancer, Vol. 5, No. 7, 12.2007, p. 433-437.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The AKT inhibitor perifosine in biochemically recurrent prostate cancer
T2 - A phase II California/Pittsburgh cancer consortium trial
AU - Chee, Karen G.
AU - Longmate, Jeff
AU - Quinn, David I.
AU - Chatta, Gurkamal
AU - Pinski, Jacek
AU - Twardowski, Przemyslaw
AU - Pan, Chong-Xian
AU - Cambio, Angelo
AU - Evans, Christopher P
AU - Gandara, David R
AU - Lara, Primo N
PY - 2007/12
Y1 - 2007/12
N2 - Background: Perifosine is an oral alkylphospholipid that inhibits cancer cell growth through decreased Akt phosphorylation. We conducted a phase II trial of perifosine in patients with biochemically recurrent, hormone-sensitive prostate cancer. Patients and Methods: Eligible patients had histologically confirmed prostate cancer, previous prostatectomy and/or radiation therapy, and rising prostate-specific antigen (PSA) without radiographic evidence of metastasis. Previous androgen deprivation therapy < 9 months in duration (completed ≥ 1 year before registration) was allowed. The primary endpoint was PSA response, defined as a decrease by ≥ 50% from the pretreatment value. Treatment was comprosed of a loading dose of perifosine 900 mg orally on day 1, then 100 mg daily starting 24 hours later. Results: Of 25 patients, 24 were evaluable for response. After a median follow-up of 8 months, 5 patients (20%) had a reduction in serum PSA levels, but none met criteria for PSA response. Three patients immediately progressed with no response to therapy. Median progression-free survival was 6.64 months (range, 4.53-12.81 months). No change in the PSA doubling time (7 months) was observed before and after treatment initiation. Dose-limiting toxicities (all grade 3) included hyponatremia, arthritis, hyperuricemia, and photophobia. Conclusion: Although well tolerated, perifosine did not meet prespecified PSA criteria for response as a single agent in biochemically recurrent prostate cancer. However, 20% of patients had evidence of PSA reduction, suggesting modest single-agent clinical activity. The role of perifosine in combination with androgen deprivation or chemotherapy is currently under investigation.
AB - Background: Perifosine is an oral alkylphospholipid that inhibits cancer cell growth through decreased Akt phosphorylation. We conducted a phase II trial of perifosine in patients with biochemically recurrent, hormone-sensitive prostate cancer. Patients and Methods: Eligible patients had histologically confirmed prostate cancer, previous prostatectomy and/or radiation therapy, and rising prostate-specific antigen (PSA) without radiographic evidence of metastasis. Previous androgen deprivation therapy < 9 months in duration (completed ≥ 1 year before registration) was allowed. The primary endpoint was PSA response, defined as a decrease by ≥ 50% from the pretreatment value. Treatment was comprosed of a loading dose of perifosine 900 mg orally on day 1, then 100 mg daily starting 24 hours later. Results: Of 25 patients, 24 were evaluable for response. After a median follow-up of 8 months, 5 patients (20%) had a reduction in serum PSA levels, but none met criteria for PSA response. Three patients immediately progressed with no response to therapy. Median progression-free survival was 6.64 months (range, 4.53-12.81 months). No change in the PSA doubling time (7 months) was observed before and after treatment initiation. Dose-limiting toxicities (all grade 3) included hyponatremia, arthritis, hyperuricemia, and photophobia. Conclusion: Although well tolerated, perifosine did not meet prespecified PSA criteria for response as a single agent in biochemically recurrent prostate cancer. However, 20% of patients had evidence of PSA reduction, suggesting modest single-agent clinical activity. The role of perifosine in combination with androgen deprivation or chemotherapy is currently under investigation.
KW - Alkylphospholipids
KW - Androgen deprivation therapy
KW - Prostate-specific antigen
UR - http://www.scopus.com/inward/record.url?scp=38949099997&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38949099997&partnerID=8YFLogxK
U2 - 10.3816/CGC.2007.n.031
DO - 10.3816/CGC.2007.n.031
M3 - Article
C2 - 18272025
AN - SCOPUS:38949099997
VL - 5
SP - 433
EP - 437
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
SN - 1558-7673
IS - 7
ER -