Taxotere® Treatment for Prostate Cancer
The TAX 327 clinical trial by Tannock and colleagues is the first phase III trial
to demonstrate a significant benefit in androgen-independent (hormone-refractory)
metastatic prostate cancer (AIPC).1,2
TAX 327, completed in January 2006, compares Taxotere®(docetaxel) + prednisone with mitoxantrone
+ prednisone. According to the study researchers, Taxotere® + prednisone is the only
treatment regimen proven to significantly extend survival in patients with metastatic
AIPC.1,2
The Taxotere® + prednisone group was randomized to two arms:
- Taxotere® 75 mg/m2 q 3 weeks + prednisone 5 mg po bid continuously (n=335)*
- Taxotere® 30 mg/m2 weekly + prednisone 5 mg po bid continuously (n=334)1–3*
*Administration of study medication: Taxotere® administered every 3 weeks for 10 cycles; Taxotere® are 2=Taxotere® administered for the first 5 weeks of 2 6-week cycle for 5 cycles; control arm=mitoxantrone administered every 3 weeks for 10 cycles
The weekly Taxotere® arm demonstrated no overall survival advantage compared with the mitoxantrone arm.
The mitoxantrone + prednisone group received mitoxantrone 12 mg/m2 q 3 weeks + prednisone
5 mg po bid continuously (n=337).1–3
Proven Prolonged Survival
In TAX 327, the Taxotere® q 3 weeks + prednisone group showed significantly
longer median survival vs. mitoxantrone + prednisone (18.9 months vs. 16.5 months, P=.0094).1,2
- Taxotere® q 3 weeks + prednisone: 95% CI, 17.0–21.2 months
- Mitoxantrone + prednisone: 95% CI, 14.4–18.6 months1,2
TAX 327 Survival Rates1,2
Significantly longer median survival
24% reduced risk of mortality
27.6% 2-year survival advantage
The Taxotere® q 3 weeks + prednisone group also showed a 24% reduced risk of mortality.1,2
Well Established Safety Profile3
The TAX 327 trial also demonstrated a well-established safety profile in Taxotere® + prednisone patients vs. mitoxantrone + prednisone
- Incidence of most grade 3/4 adverse events < 5%
| Adverse event |
Grade 3/4§ |
Taxotere® q 3 wk + prednisone
% of patients
n=332 |
Mitoxantrone = prednisone
% of patients
n=335 |
| Hermatologic |
|
|
| Anemia |
4.9 |
1.8 |
| Neutropenia |
32.0 |
21.7 |
| Thromboctopenia |
0.6 |
1.2 |
| Febrile neutropenia± |
NA |
NA |
| Infection |
5.7 |
4.2 |
| Toxic Death¶ |
0.3 |
0.6 |
| Non-hematologic |
|
|
| Epistaxis |
0.3 |
0.0 |
| Allergic reactions |
0.6 |
0.0 |
| Fluid Retention# |
0.6 |
0.3 |
| Weight gain# |
0.3 |
0.0 |
| Peripheral edema# |
0.3 |
0.0 |
| Neuropathy sensory |
1.8 |
0.3 |
| Neuropathy motor |
1.5 |
0.9 |
| Rash/Desquamation |
0.3 |
0.6 |
| Alopecia** |
NA |
NA |
| Nail changes |
0.0 |
0.0 |
| Nausea |
2.7 |
1.5 |
| Diarrhea |
2.1 |
1.2 |
| Stomatitis/Pharyngitis |
0.9 |
0.0 |
| Taste disturbance |
0.0 |
0.0 |
| Vomiting |
1.5 |
1.5 |
| Anorexia |
1.2 |
0.3 |
| Cough |
0.0 |
0.0 |
| Dyspnea |
2.7 |
0.9 |
| Cardiac left-ventricular function‡ |
0.3 |
1.2 |
| Fatigue |
4.5 |
5.1 |
| Myalgia |
0.3 |
0.9 |
| Tearing |
0.6 |
0.0 |
| Arthralgia |
0.6 |
1.2 |
Grades 1 and 2 refer to mild and moderate adverse events, respectively.
§Grade 3 adverse events are classified as severe; grade 4 adverse events are classified as life-threatening or debilitating.
± A grade 3/4 rating for febrile neutropenia is not applicable (NA) because defined as grade 4 neutropenia with grade ≥ 1 fever (≥38°C) without infection.
¶ A grade 3/4 rating is not applicable (NA) to toxic death because it is defined as grade 5. Toxic death is both a hematologic and non-hematologic adverse event. The percentages listed are for deaths due to drug-related toxicity within 30 days of last infusion.
# Related to treatment.
** A grade 3/4 rating for alopecia is not applicable (NA) because alopecia is not defined as severe, life threatening, or debilitating; it is therefore classified as grade 1 or 2.
# Related to treatment.
‡ Left-ventricular function tests (eg, radionuclide angiography or echocardiography)
evaluate how effectively myocardium pumps blood, measured in “ejection fraction”
of blood. Patients with grade 3/4 left-ventricular systolic dysfunction have congestive heart failure with ejection fractions 40%.
High number of patients completing planned course of therapy
Out of 10 scheduled cycles, patients in the Taxotere® q 3 weeks + prednisone arm
completed a median of 9.5 cycles vs. 5.0 cycles in the mitoxantrone + prednisone
arm.1
- Discontinuation rate due to disease progression was 37.9% for the Taxotere® q 3 weeks
+ prednisone arm and 56.4% for the mitoxantrone + prednisone arm.
- Discontinuation rate due to adverse events was 10.7% for the Taxotere® q 3 weeks
+ prednisone arm and 9.8% for the mitoxantrone + prednisone arm.3
Additionally, Taxotere® q 3 weeks + prednisone was well tolerated in the elderly
population.2
References
- Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. Engl J Med. 2004;351:1502-1512.
- Taxotere® Prescribing Information. Bridgewater, NJ: sanofi-aventis U.S. LLC; November 2007.
- Data on file, sanofi-aventis. Clinical study report: a multicenter phase III randomized trial comparing Taxotere® administered either weekly or every three weeks in combination with prednisone versus mitoxantrone in combination with prednisone for metastatic hormone-refractory prostate cancer. Study number RP56976-V-327. 2004.