178

Practical Urology: EssEntial PrinciPlEs and PracticE

receive a cisplatin-containing combination che-

gastrointestinal toxicity, cardiac toxicity, neu-

motherapy

regimen

(creatinine

clear-

ropathy, and alopecia. Therefore, urologists

ance ³60 mL/min, PS, comorbidity). To date,

have been using second-line hormonal manip-

there is no generally accepted definition for “fit”

ulations such as ketoconazole and aminoglute-

or “unfit” patients. Carboplatin-containing

thimide. Recently abiraterone has been tested

combination chemotherapy or single agents are

with success after first-line hormonal manipu-

suggested as first-line treatment in patients

lation. Over the past 2 decades, chemotherapy

“unfit” for cisplatin. It should be noted that car-

for advanced prostate cancer has evolved from

boplatin-combination chemotherapy is less

a therapy having a limited role in HRPC to a

effective than cisplatin-based chemotherapy in

therapy that may provide a short survival ben-

terms of complete response and survival.9 At

efit, but more importantly that can provide

present, there is no standard of care for the

effective palliation of the symptoms.

treatment of patients with bladder cancer after

failure of cisplatin-containing combination

Estramustine, Mitoxantrone,

chemotherapy in the first-line setting. If the

patient has a good performance status, single

and Docetaxel

agents or paclitaxel/gemcitabine can be consid-

ered as second-line treatment. Attempts to

To date,three drugs (estramustine,mitoxantrone,

improve second-line treatment have directed to

and docetaxel) have gained approval by the US

the assessment of single agents such as vinflu-

Food and Drug Administration (FDA) for first-

nine and pemetrexed9 and multidrug combina-

line chemotherapy in HRPC. Estramustine and

tions with cytotoxic and targeted agents,

mitoxantrone could not cause a survival advan-

including trastuzumab and bevacizumab.19

tage compared to control treated patients with

Post-chemotherapy surgical resection after a

HRPC, although they did reduce pain. More

complete or partial response may contribute to

recently, data from two large randomized phase

long-term disease control in selected patients.9

III trials, TAX 327 and SWOG 9916, have demon-

strated an acceptable tolerability and a signifi-

Conclusion

cant improvement in OS for patients with HRPC

treated with three-weekly docetaxel, although

Further investigations and randomized studies

the increase was small (<2.5 months).20-22 In the

SWOG 9916 and TAX 327 study, the median sur-

are required to clarify the exact role of chemo-

vival was 17.5 and 18.9 months in the three-

therapy

in

patients

with bladder

cancer.

weekly

docetaxel

group, while

15.6 and

Progress in the understanding of the molecular

16.5 months in the mitoxantrone group. Weekly

biology of bladder cancer and identification of

docetaxel in the TAX 327 study did not result in a

newer drug combinations and targeted agents

significant survival benefit. Patients treated with

directed

at

specific molecular pathways will

three-weekly docetaxel plus prednisone in the

provide less toxic and perhaps more active reg-

TAX 327 study experienced improved pain relief

imens. In the meantime, bladder removal con-

and quality of life compared to mitoxantrone

tinues to be a necessary life-saving operation

plus prednisone.21,22

The combination of three-

that must be considered in all high-risk cases

weekly docetaxel with estramustine in the SWOG

that fail to immediately respond to other treat-

9916 study was associated with increased toxicity

ment options.

and did not appear to have improved efficacy

compared with the three-weekly docetaxel plus

Prostate Cancer

prednisone regimen in the TAX 327 study. These

findings supported the approval of docetaxel-

based chemotherapy for the treatment of HRPC

Traditionally, chemotherapy has not been

by the FDA in May 2005. Three-weekly docetaxel

offered as routine treatment for patients with

(75 mg/m2) plus low-dose prednisone regimen

hormone refractory prostate cancer (HRPC)

has widely become the current standard of care

because of treatment-related toxicity and poor

as first-line chemotherapy for treating HRPC.23

responses. Major adverse events associated

An updated survival analysis of TAX 327 showed

with chemotherapeutics are myelosuppression,

that the

significant

improvement

in survival