NcXHF

HERNANDEZ-AYA AND HUSSAIN
nifıcant effects on sensory nerves, and 1% on motor nerves,
and 1 of the 397 patients who received early docetaxel died as
a result of treatment. The cause of death was prostate cancer
in 84 patients in the ADT plus docetaxel arm (83.2%) and 112
patients in the ADT-alone arm (83.6%). 37
In summary, this study shows that starting docetaxel along
with hormone therapy in men with newly diagnosed hormonesensitive
prostate cancer improved OS by more than 13.6
months in comparison with standard hormone therapy alone.
The bulk of the benefıt appears to be in patients with highvolume
disease. This striking survival benefıt supports the use of
upfront docetaxel in hormone-sensitive prostate cancer, especially
in patients with high-volume disease.
Before CHAARTED, docetaxel was reserved for patients
relapsing after initial ADT. In that setting, docetaxel produced
only 2 to 3 months prolongation of survival. More recently,
abiraterone, enzalutamide, and radium-223 also
produce 3- to 5-month prolongations of median survival
when they are given as successive single agents. The magnitude
of survival improvement with docetaxel plus ADT upfront
is unprecedented. The most likely explanation is
biologic; therapy works best when it is multitargeted, administered
in a lesser disease volume as a preemptive strike before
adaptive resistance. Other potential factors include
better drug tolerance and less toxicity in less sick patients.
CONCLUSION
The heterogeneity of prostate cancer and the diverse
mechanisms of resistance support a multitargeted approach
to maximize the antitumor impact. The totality of
the current data would favor not delaying the use of docetaxel
chemotherapy; pending the fınal peer-review publication
of the CHAARTED trial, results strongly suggest that
survival benefıts of docetaxel are signifıcantly higher when
given in combination with ADT early in the course of mH-
SPC and that the combination has a more profound return
on investment as compared with sequential therapy. The unprecedented
survival benefıts of this chemo-hormonal approach
appear to be related to the better antitumor effect as reflected
by higher rates of undetectable PSA levels and longer median
time to castration resistance and clinical progression. Overall,
patients tolerated therapy very well. Therefore, patients
with newly diagnosed mHSPC who are deemed chemotherapy
eligible, especially those with high-volume disease,
should be counseled regarding this data and offered combination
therapy.
Disclosures of Potential Conflicts of Interest
Relationships are considered self-held and compensated unless otherwise noted. Relationships marked “L” indicate leadership positions. Relationships marked “I” are those held by an immediate
family member; those marked “B” are held by the author and an immediate family member. Institutional relationships are marked “Inst.” Relationships marked “U” are uncompensated.
Employment: None. Leadership Position: None. Stock or Other Ownership Interests: None. Honoraria: None. Consulting or Advisory Role: Maha
Hussain, J&J, Synthon Biopharmaceuticals. Speakers’ Bureau: None. Research Funding: Maha Hussain, Astellas Pharma (Inst), Bayer (Inst), Genentech
(Inst), Medivation (Inst), Millennium (Inst), Pfizer (Inst). Patents, Royalties, or Other Intellectual Property: Maha Hussain, Method of Treating Cancer,
Serial No. 61/481/671. Expert Testimony: None. Travel, Accommodations, Expenses: None. Other Relationships: None.
References
1. Tangen CM, Hussain MH, Higano CS, et al. Improved overall survival
trends of men with newly diagnosed M1 prostate cancer: a SWOG phase
III trial experience (S8494, S8894 and S9346). J Urol. 2012;188:1164-
1169.
2. Chen CD, Welsbie DS, Tran C, et al. Molecular determinants of resistance
to antiandrogen therapy. Nat Med. 2004;10:33-39.
3. Waltering KK, Helenius MA, Sahu B, et al. Increased expression of androgen
receptor sensitizes prostate cancer cells to low levels of androgens.
Cancer Res. 2009;69:8141-8149.
4. Steinkamp MP, O’Mahony OA, Brogley M, et al. Treatment-dependent
androgen receptor mutations in prostate cancer exploit multiple mechanisms
to evade therapy. Cancer Res. 2009;69:4434-4442.
5. Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisone or
mitoxantrone plus prednisone for advanced prostate cancer. N Engl
J Med. 2004;351:1502-1512.
6. Petrylak DP, Tangen CM, Hussain MH, et al. Docetaxel and estramustine
compared with mitoxantrone and prednisone for advanced refractory
prostate cancer. N Engl J Med. 2004;351:1513-1520.
7. de Bono JS, Oudard S, Ozguroglu M, et al. Prednisone plus cabazitaxel
or mitoxantrone for metastatic castration-resistant prostate cancer
progressing after docetaxel treatment: a randomised open-label trial.
Lancet. 2010;376:1147-1154.
8. de Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased
survival in metastatic prostate cancer. N Engl J Med. 2011;364:1995-
2005.
9. Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone in metastatic prostate
cancer without previous chemotherapy. N Engl J Med. 2013;368:138-
148. Epub 2012 Dec 10.
10. Scher HI, Fizazi K, Saad F, et al. Increased survival with enzalutamide
in prostate cancer after chemotherapy. N Engl J Med. 2012;
367:1187-1197.
11. Beer TM, Armstrong AJ, Rathkopf DE, et al. Enzalutamide in metastatic
prostate cancer before chemotherapy. N Engl J Med. 2014;371:
424-433.
12. Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for
castration-resistant prostate cancer. N Engl J Med. 2010;363:411-422.
13. Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and
survival in metastatic prostate cancer. N Engl J Med. 2013;369:213-223.
e268
2015 ASCO EDUCATIONAL BOOK | asco.org/edbook