|
Sunitinib (Sutent®) Summary Table
A Potential ≥ 2nd line treatment
for HRPC patients who have failed 1st line taxotere.
Combined with Taxotere it might
also be a better 1st line chemo than taxotere alone
Author: Howard Hansen
15 January 2009
See the main page on Sunitinib
for additional information.
Definitions
-
Tyrosine
kinase inhibitor - the NCI's definition is "A drug that interferes with cell
communication and growth and may prevent tumor growth. Some tyrosine kinase
inhibitors are used to treat cancer." Abbreviation is TKI.
-
FLT3 - FMS-like
tyrosine kinase-3 gene.
-
PDGFRs -
Platelet Derived Growth Factor Receptor - alpha and beta.
-
RET - rearranged
during transfection. An oncogene.
-
VEGFRs -
Vascular endothelial growth factor receptor. They are numbered 1, 2 and
3. VEGF is the key mediator of angiogenesis, endothelial cell growth and
vascular permeability. It binds and activates its receptor.
-
dysgeusia (impaired sense of taste).
-
MDR - median duration of response.
-
PFS - Median Progression Free Survival.
Introduction
The following table summarizes the results of studies to date, either with
single agent sunitinib or sunitinib combined with another drug such as
docetaxel
(taxotere.) All patients had HRPC (CRPC) disease.
| |
Reference |
Phase of trial;
No. of Patients; Patient characteristics |
Combination |
PSA Response Rate of
Combination |
Measurable Disease RR |
PFS
of combination and MDR |
| |
A. Zurita et al(2), 2007 |
I, 25 patients, chemo-naïve, Metastatic |
Sunitinib 37.5mg/day, 2wks on, 1 off Taxotere 75mg/mm2, 21 day
cycle. Predisone 5mg 2x/day. |
40% (10 of 25 patients) |
20% (4 of 20 patients) partial RR; 55% (11 patients) stable
disease. |
|
| A. Zurita et al (4)ASCO 2009
#5166 |
II, 55; Chemo-naive patients only. |
Sunitinib, 37.5mg days 1-14.
Taxotere/prednisone, 75mg/m2 IV day 1, prednisone 5mg 2x/day,
days 1-21.
|
PSA RR (≥ 50%
decrease) 31 pts (56%). |
13 of 33 pts with measurable
disease (39%) had partial responses. 7 (21%) had an
initial PR.
Progressive disease in 16.
|
- |
| |
A. Zurita et al (2) 2007 |
I, 25 patients, chemo-naive, Metastatic, lead in study. |
Sunitinib, 50mg/day, 4 wks on, 2(?) off. |
PSA drop of 40%: 7 patients. 3 decreased >
50%.
12/25 patients had a mean PSA rise of 273%
which dropped during the 2 week rest period. |
- |
- |
| P.O. Periman et al (3)ASCO 2008 #5157. |
II, 19 of planned 36. 1-2 prior chemotherapies allowed (incl
docetaxel). |
Sunitinib, 50mg/day, 4 weeks on, 2 weeks off. |
PSA 50% decrease RR 3 (9%)
PSA 30% decrease RR 7(21%) |
- |
12 wk PFS goal was > 30%, achieved 78.9%. Median PFS 21.1 wks. |
| Clinical Trials that have not had
any results published (yet). HRPC patients. |
| SMART |
Phase II, after docetaxel |
Sunitinib, 50mg/day, 4 weeks on, 2
off. |
- |
- |
- |
| PROSUT |
Phase II, after docetaxel. |
Sunitinib, 37.5mg continuously 6 wk cycles. |
- |
- |
- |
| SUN 1120 |
Phase III,
after
docetaxel.
Placebo
control. |
Sunitinib, 37.5mg continuously plus 5mg 2x/day
prednisone (arm A) |
- |
- |
- |
Current Clinical Trials involving Sutent and HRPC Disease
Sutent Maintenance After Response to Taxotere (SMART) -
Phase II. SU011248 (study medication) will be given at 50 mg/day as a
single agent for 4 consecutive weeks followed by a 2 week rest period to
form a complete cycle of 6 weeks. Study medication will be orally self
administered once daily without regard to meals beginning on Day 1 of the
study. Cycles will be repeated in the absence of unacceptable toxicity or
disease progression
http://clinicaltrial.gov/ct2/show/NCT00550810?term=sutent&recr=Open&rank=33
An Open-Label Phase II Study With SUTENT in Patients
Suffering From Hormone Refractory Prostate Cancer (PROSUT). After docetaxel,
study will investigate the efficacy of sunitinib (SUTENT) given orally at a
dose of 37.5 mg continuously, for 6 cycles of 6 consecutive weeks. Patients
who are still responders after 6 cycles will be treated until disease
progression, pain progression, unacceptable toxicity or death due to any
cause. Dose increase or reduction of 12.5 mg increments and change of
schedule is recommended based on individual safety and tolerability.
http://clinicaltrial.gov/ct2/show/NCT00748358?term=sutent&recr=Open&rank=52
A Multicenter, Randomized, Double-Blind,
Phase III Study Of Sunitinib Plus Prednisone Versus Prednisone In Patients
With Progressive Metastatic Hormone-Refractory Prostate Cancer After Failure
Of A Docetaxel-Based Chemotherapy Regimen (SUN 1120). Sunitinib plus prednisone vs prednisone and a
placebo. Dose of sunitinib is 37.5mg administered on a continuous
daily regimen. Prednisone 5mg 2x/day.
http://clinicaltrial.gov/ct2/show/NCT00676650?term=sutent&recr=Open&rank=63
Reference (6) by G. Sonpavde et al (6) outline a
phase II clinical trial of sunitinib after previous docetaxel
chemotherapy(1-2 total previous chemotherapies. The trial enrolled 34
patients. Dose of sunitinib was planned to be 50mg, once daily for 4 weeks
of every 6 week cycle. This trial might be that described in reference (3).
Author: Howard Hansen, 15 January 2009, updated 29 May
2009.
References
1.
Cumashi A, Tinari N, Rossi C, Lattanzio R, Natoli C, Piantelli M, Iacobelli
S.,
Sunitinib malate (SU-11248) alone or in combination with low-dose docetaxel
inhibits the growth of DU-145 prostate cancer xenografts, Cancer Lett. 2008 Jun 27. [Epub ahead
of print].
2.
A. Zurita, N.D. Shore, M.F. Kozloff, C.W. Ryan, T.M. Beer, E. Chow
Maneval, I. Chen, C.J. Logothetis, A phase I/II study of sunitinib in combination with
docetaxel (dcx) and prednisone (pdn) in patients with metastatic
castrate-resistant prostate cancer (mCRPC), European Journal of Cancer Supplements, Vol 5 No 4, Page 287,
ECCO 14 - the European Cancer Conference Abstract # 4025,
Barcelona, Spain, 23 - 27 September 2007.
3.
P. O. Periman, G. Sonpavde, D. M. Bernold, D. J. Weckstein, A. Williams, F.
Zhan, K. A. Boehm, L. Asmar, T. E. Hutson,
Sunitinib malate for metastatic castration resistant prostate cancer
following docetaxel-based chemotherapy,
J Clin Oncol 26: 2008 (May 20 suppl; abstract # 5157). Information in the
table updated to what was presented at the conference.
4.
A. J. Zurita, G. Liu, T. Hutson, M. Kozloff, N. Shore, G. Wilding, C. J.
Logothetis, I. Chen, E. Chow Maneval, D. George, Sunitinib in combination
with docetaxel and prednisone in patients (pts) with metastatic
hormone-refractory prostate cancer (mHRPC), J Clin Oncol 27:15s, 2009 (suppl;
abstr 5166).
5.
A.J. Zurita, C.J. Logothetis, G. Liu, G. Wilding, T.E. Hutson, I.
Chen,
E. Chow-Maneval, D.J. George, SUNITINIB IN COMBINATION WITH DOCETAXEL AND
PREDNISONE IN PATIENTS WITH METASTATIC HORMONE REFRACTORY
PROSTATE CANCER (MHRPC), European Society of Medical Oncologists 2008 (ESMO 2008.)
Supplement: Abstract Book of the 33rd ESMO Congress, Stockholm, Sweden 12-16
September 2008, Annals of Oncology, Volume 19, Supplement 8, September 2008,
Abstract # 615P. The most
common
treatment-related adverse events were diarrhea (50%), neutropenia (44%),
fatigue
(33%), nausea (33%) and dysgeusia (altered taste) (28%).
6.
Sonpavde G, Hutson TE, Berry WR, Boehm KA, Asmar L.,
Phase II trial of sunitinib for the therapy of progressive metastatic
castration-refractory prostate cancer after previous docetaxel chemotherapy,
Clin Genitourin Cancer. 2008 Sep;6(2):134-7.
7. M. Smith, P. Kantoff, M. Regan, D. Kaufman, M. D. Michaelson, Phase II
study of sunitinib malate in men with advanced prostate cancer, Meeting:
ASCO 2008 Genitourinary Cancers Symposium, Abstract No: 198.
8.
David H. Garfield, Pascal Wolter, Patrick Schöffski, Aleck Hercbergs, and
Paul Davis, Documentation of Thyroid Function in Clinical Studies With Sunitinib: Why
Does It Matter?
JCO Nov 1 2008: 5131–5132. First published on Sep 29 2008;
10.1200/JCO.2008.18.8680.
In Reply
Harold J. Burstein, Kathy D. Miller, Mark A. Socinski, and Leonard B. Saltz
JCO Nov 1 2008: 5132–5133. First published on Sep 29 2008;
10.1200/JCO.2008.19.0645.
|
