The study cohort consisted of 380 patients enrolled in 17 different phase-I and phase-II protocol chemotherapy studies for the treatment of AIPC at our institution between 1988 and 1995. One patient of unknown ethnicity was excluded from the analysis. Chemotherapy treatment regimens stratified by median survival are presented in Table 1. For purposes of analysis, treatment regimens were categorized into two ordinal strata by median patient survival (Group 1 >12 months, Group 2 <12 months). Mean age of the cohort was 65.1 years (median 66 years, 95% confidence interval (CI), 64.4 to 65.9) with two- and three-year Kaplan-Meier survival rates of 24.5% and 11.9%, respectively, at a median follow-up of 13.9 months. There was only one survivor beyond 134 months.

Table 1. Patient Survival by Chemotherapeutic Treatment Group

Treatment Group Number of Patients Median Mean 95% CI
Group 1

252

/6.9

22.1

/9.6, 24.6

TNP-470 (angiogenesis inhibitor) (phase-ll)

30 21.4 25.0 16.0, 34.0

doxorubicin

38 19.7 24.5 17.9, 31.1

Tumor necrosis factor and actinomycin-D

20 19.3 23.4 14.8, 32.1

Alternating KA/VE*

38 17.9 21.2 15.3, 27.4

Estramustine and vinblastine

28 17.4 16.9 11.5, 22.2

Paclitaxel

15 15.8 22.3 14.2, 30.4

Doxorubicin and suramin

19 14.4 22.2 12.4, 32.1

Estramustine, vincristine, and mitomycin

46 13.6 23.8 15.9,31.7

Strontium and doxorubicin

18 12.8 16.1 11.0,21.2
Group 2 /27 9.5

13.8

/0.8, /6.8

Fluoxetine

13 11.7

24.6

3.8, 45.4

Suramin (phase-ll)

17 10.9 12.2 8.2, 16.2

Suramin

8 10.3 16.1 0.39,31.9

Vincristine, doxorubicin, and mitomycin С

50 9.9 11.6

9.0, 14.1

Strontium

16 9.5 16.2 3.5, 29.0

TNP-470 (phase-l)

7 9.0 17.7 0.8, 34.6

Interferon and flutamide

9 5.1 8.9 0.14, 27.6

 

7 2.5 7.1 0.27, 14.0

Total

379 13.9 19.3 17.3, 21.3

Univariate Cox regression analysis failed to reveal an association between survival and patient race (Table 2). Although Hispanic men had a shorter median survival time (10.1 months) compared with Caucasian (14.1 months) and African-American men (13.4 months), the difference was not statistically significant. Prognostic factors for survival on univariate analysis included age, (<70 versus >70), serum hemoglobin, alkaline phosphatase, serum PSA (>200 ng/ml), osseous stage, number of organ sites of metastasis, bone scan extent-of-disease (>20 sites), time from androgen deprivation to AIPC and treatment group (Table 1). In multivariate analysis, independent predictors of survival were treatment group (HR=1.68 I versus II, 95% CI [1.33-2.12]), time from androgen ablation to AIPC (HR=0.994 per month increase, 95% CI [0.990-0.998]), osseous stage (HR=1.49 stage-I versus -II, 95% CI [1.11-1.99]), the number of metastatic sites (HR-1.31, 95% CI [1.15-1.49]), and serum hemoglobin (HR=0.87 gm/dl increase, 95% CI [0.81- 0.94]), and age (HR=1.51 for > versus <70 years, 95% CI [1.18-1.94]) (Table 3). There was no difference in treatment group assignment, time to AIPC, number of metastatic sites or osseus stage by race/ethnic group. However, African-American and Hispanic patients were younger (median age 63 years, both groups p=0.07 and 0.02, respectively) when compared with Caucasian patients (median age=65years). African-American patients also exhibited significantly lower serum hemoglobin levels (11 .3 mg/dl versus 12.5 mg/dl) compared to Caucasian patients (p=0.001). canadian cialis

Table 2. Univariate Cox Regression Analysis of Prognostic Factors for Survival

Patients Hazard Ratio

95% CI

P Value
Age<70

>70

280 99 100R1.325

1.053-1.669

0.017
Race or Ethnic Group Caucasian African-American Hispanic 329 27 23 1.00R1.24

1.37

0.83-1.83 0.90-2.09

0.22 0.29 0.15

Log serum PSA level(ng/ml) 379 1.14

1.06-1.22

O.0001
Hemoglobin level(gm/dl) 379 0.78

0.74-0.83

O.0001
Log alkaline phosphatase (IU/L) 379 1.46

1.30-1.65

O.0001
Osseous Stage Stage 1 Stage 2 230 149 1.00R 2.10

1.70 – 2.59

O.0001
Number of metastatic sites 379 1.32

1.16- 1.50

0.0001
Bone Scan Extent of disease Level 1 (<6 sites) Level 2 (6 to 20 sites) Level 3 (>20 sites) Level 4 (Superscan) 87 66 188 38 1.00R 1.15 1.84 2.99 0.83-1.58 1.42-2.39 2.03-4.39

0.39 0.0001 0.0001

Time to AIPC (months) 379 0.995

0.991-0.999

0.010
Treatment Group Group 1 Group 2 252 127 1.00R 1.75

1.41-2.18

0.0001
*R = reference group

The effect of these variables on survival is presented in Table 4 for various categories and reveals a doubling of survival based upon the more favorable category of treatment, osseous stage, time to AIPC and serum hemoglobin. Smaller increments in survival were gained by age <70 and having less than three different metastatic sites. eriacta 100 mg

Table 3. Multivariate Cox Regression Analysis of Prognostic Factors for Survival

Adjusted Hazard Ratio 95% CI

Wald

P Value
Treatment Group Group 1 Group 2 1.00R* 1.68

1.33-2.12

19.29

O.0001

Time to AIPC months) 0.994

0.990-0.998

7.25

0.007

Osseous Stage Stage 1 Stage 2 1.00R 1.49

1.11-1.99

6.96

0.008

Number of metastatic sites 1.31

1.15-1.49

16.08

O.0001

Hemoglobin(gm/dl) 0.87

0.81-0.94

14.46

O.0001

Age (years)<70

>70

1.00R 1.519

1.189-1.94

11.09

0.001

Log alkaline phosphatase(IU/L) 1.11

0.95-1.34

1.82

0.178

Bone Scan Extent of Disease Level 1 (<6 sites) Level 2 (6 to 20 sites) Level 3 (>20 sites) Level 4 (Superscan) 1.00R 1.02 1.16 1.00 0.72-1.43 0.83-1.64 0.60-1.69 0.01 0.75 0.00 0.70 0.91 0.39 0.99
Log serum PSA (ng/ml) 1.02

0.95-1.098

0.35

0.55

Ethnicity Caucasian African-American Hispanic 1.00R 0.95 1.27 0.63-1.44 0.81-1.99 0.06 1.09 0.55 0.81 0.30
*R = reference group

Table 4. Survival Stratified by Prognostic Factors

Number Patients

Median Survival (Months)

95% CI

Pairwise Log Rank Tests

All patients

379 13.9

12.6, 15.1

Age Group>70

<70

99 280 11.5 14.9 8.8, 14.2 13.2, 16.7

0.016

Treatment Group Group 1 Group 2 252 127 16.8 9.5 14.5, 19.0 7.9, 11.0

O.0001

Osseous Stage Stage 1 Stage 2 230 149 17.7 8.9 15.3, 20.2 7.6, 10.2

O.0001

Time to AIPC (months)

>12

<12

312 67 15.1 8.0 13.3, 16.9 6.2, 9.8

O.0001

Number of Metastatic Sites1 (1) 2(2) >3 (3) 223 93 63 15.1 13.2 10.9 12.7, 17.5 11.1, 15.3 8.1, 13.6

1 vs. 2 N.S.

1           vs. 3 O.0001

2           vs. 3 0.0078

Hemoglobin (g/dL)

>12

<12

Missing

213 165 1 18.1 9.0 15.3, 20.8 7.4, 10.6

O.0001

NS = not significant