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ORIGINAL ARTICLE
Year : 2015  |  Volume : 52  |  Issue : 4  |  Page : 658-660
 

Line of abiraterone acetate in castration-resistant metastatic prostate cancer - Does it matter? report of a multi-institutional experience


1 Department of Medical Oncology, Akdeniz University Hospital, Antalya, Turkey
2 Medical Oncology, Antalya Research and Practice Hospital, Antalya, Turkey
3 Medical Oncology, Afyon Kocatepe University, Afyon, Turkey
4 Medical Oncology, Antalya Medstar Hospital, Antalya, Turkey

Date of Web Publication10-Mar-2016

Correspondence Address:
S Gunduz
Department of Medical Oncology, Akdeniz University Hospital, Antalya
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.178379

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 » Abstract 


OBJECTIVE: We present our data comparing retrospectively the efficacy of abiraterone and cabazitaxel in patients who progress after docetaxel treatment. PATIENTS AND METHODS: The study included 56 patients diagnosed with hormone-refractory metastatic prostate cancer who were previously treated with abiraterone therapy at four oncology centers in Turkey. RESULTS: With abiraterone, the patients had a median progression-free survival (PFS) of 5.9 months (95% confidence interval (CI) for hazard ratio (HR) (4.4–7.4)) and an overall survival of 13.4 months (95% CI for HR (5.5–21.3)). When we compared the disease-free survival (DFS) of reference patients treated with cabazitaxel as a second-line treatment with those receiving second-line abiraterone therapy, there was no significant difference. (PFS = 5.9 months with cabazitaxel vs. 6.7 months with abiraterone, P = 0.213). CONCLUSION: This study has shown that in our experience abiraterone acetate is an effective agent in metastatic castration-resistant prostate cancer (mCRPC) regardless of the line of treatment.


Keywords: Abiraterone, cabazitaxel, castration-resistant prostatate cancer


How to cite this article:
Gunduz S, Bozcuk H, Yıldız M, Goksu S S, Uysal M, Arslan D, Tatlı A, Mutlu H, Coşkun H, Ozdogan M. Line of abiraterone acetate in castration-resistant metastatic prostate cancer - Does it matter? report of a multi-institutional experience. Indian J Cancer 2015;52:658-60

How to cite this URL:
Gunduz S, Bozcuk H, Yıldız M, Goksu S S, Uysal M, Arslan D, Tatlı A, Mutlu H, Coşkun H, Ozdogan M. Line of abiraterone acetate in castration-resistant metastatic prostate cancer - Does it matter? report of a multi-institutional experience. Indian J Cancer [serial online] 2015 [cited 2019 Dec 7];52:658-60. Available from: http://www.indianjcancer.com/text.asp?2015/52/4/658/178379





 » Introduction Top


Prostate cancer accounts for 28% of all newly diagnosed cancer cases among men in the USA, ranking second as a cause of cancer-related mortality.[1] Since 2010, the U.S. Food and Drug Administration (FDA) has approved four new drugs shown to increase overall survival in patients with hormone-refractory metastatic prostate cancer: Cabazitaxel, a second-line taxane chemotherapy; sipuleucel-T, an autologous immunotherapy; abiraterone, an androgen synthesis inhibitor; and enzalutamide, an antagonist of the androgen receptor.[2]

Abiraterone acetate inhibits cytochrome P450c17, a critical enzyme in extragonadal and testicular androgen synthesis. Abiraterone plus low-dose prednisone was shown to improve overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with a docetaxel-based chemotherapy regimen, and in those who had not received chemotherapy.[3],[4],[5],[6],[7],[8] The purpose of this study was to examine retrospectively the survival data of our patients with metastatic hormone-refractory prostate cancer who received abiraterone therapy at some line during their management and to determine whether there were differences in progression-free survival (PFS) figures among patients receiving either abiraterone or cabazitaxel as second-line treatment from four centers. These centers were Akdeniz University Hospital, Antalya Medstar Hospital, Antalya Research and Practice Hospital and Afyon Kocatepe University.


 » Materials and Methods Top


Patients

The medical files of the patients with mCRPC were reviewed retrospectively. The study included 56 patients diagnosed with hormone-refractory metastatic prostate cancer previously treated with abiraterone therapy.

Disease progression in patients was defined as elevated prostate-specific antigen (PSA) level and/or increase in the dimensions of existing lesions or development of new metastases as demonstrated by radiological imaging.

Statistical analysis

Overall survival (OS) was defined as the duration between the date of onset of a treatment and the date of death. PFS was defined as the period of time between the initial administration of a treatment and the detection of the first tumor progression based on radiological criteria, elevated PSA or death. Survival was analyzed by Kaplan-Meier survival analysis and univariate Cox regression analysis. Variables with a value of P < 0.10 in the univariate analysis were also evaluated by multivariate analysis. A P value of less than 0.05 (P < 0.05) was considered as statistically significant.


 » Results Top


Patient, disease and treatment characteristics

In this study, we evaluated the data from 56 patients diagnosed with hormone-refractory metastatic prostate cancer. The median follow-up period was 40 months. The median age of the patients was 67 years (ranging from 48 to 85). The patients had developed resistance to hormone therapy after a median time of 22.8 months. The study group consisted of all patients with mCRPC from four centers between December 2011 and July 2013.

While 40 of the patients had bone metastasis (71.4%), only two patients had visceral metastasis (3.6%) and 12 patients had both bone and visceral metastasis (21.7%). In 55.4% of the patients, abiraterone was started as a second-line therapy after treatment with docetaxel, and in 5.4% the treatment was initiated before chemotherapy [Table 1].
Table 1: Baseline characteristics of patients

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Patients who had received two lines of chemotherapy or more accounted for 35.7% of the sample. The median PSA level in our patients was determined to be 125 ng/ml (range 6–3154). Of the 38 patients who had their PSA level checked in the third month after the onset of treatment, 47.7% had a decline in PSA level by more than 50%.

Survival analysis

During the treatment with abiraterone, the patients had a median PFS of 5.9 months [95% CI for HR (4.4–7.4)] and an overall survival of 13.4 months (95% confidence interval (CI) for hazard ratio (HR) (5.5–21.3)) [Figure 1] and [Figure 2]. None of the factors evaluated in this study were linked with PFS (age, pre-treatment PSA level, site of metastasis, and number of lines of chemotherapy received). In particular, when we examined the factors affecting PFS on abiraterone, we found that PFS was not affected by the number of chemotherapy lines received prior to abiraterone (P = 0.072 (95% CI for HR (5.02–7.44))) or the use of cabazitaxel before treatment (P = 0.87 (95% CI for HR (4.41–7.45))). In addition, there was no statistically significant difference between PFS in these patients and in those who had no reduction in PSA (9.8 months vs. 5.8 months, P = 0.199).
Figure 1: Progression free survival with abiraterone

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Figure 2: Overall survival with abiraterone

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When we compared the PFS of 13 patients treated with cabazitaxel as the second-line treatment to those receiving second-line abiraterone therapy (n = 30), we found no significant difference between the two groups. (PFS 5.9 months in the cabazitaxel group vs. 6.7 months in the abiraterone group, P = 0.213) [Figure 3].
Figure 3: Progression free survival in the second-line setting: Abiraterone vs cabazitaxel

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 » Discussion Top


The results of our study showed that abiraterone is a clinically effective drug in the treatment of Turkish patients with hormone-refractory prostate cancer. This was the first exploratory study comparing the effects of cabazitaxel as second-line therapy with the use of abiraterone as second-line therapy in terms of PFS, and we determined that both drugs were equally effective in the second line setting in our limited sample of Turkish patients.

Several studies have demonstrated the efficacy of abiraterone and cabazitaxel on OS in patients exhibiting progression after docetaxel-based chemotherapy. A novel tubulin-binding taxane, cabazitaxel has been shown to be superior to mitoxantrone in terms of both overall survival (15.1 vs. 12.7 months, P < 0.0001) and PFS (2.8 vs. 1.4 months).[9]

In our study, the median progression-free survival was 5.9 months (95% CI for HR (4.4–7.4) in patients treated with abiraterone, and overall survival was 13.4 months (95% CI for HR (5.5–21.3)). We did not find any predictive factor for the efficacy of abiraterone in our experience.

Bone pain is a factor predictive of skeletal-related events (SREs). Prostate cancer patients with bone metastases have increased risk of mortality, 6.6 times higher than men without bone metastases, while patients with bone metastases plus SREs have a 10.2-fold increased risk of mortality.[10],[11]

Both abiraterone and cabazitaxel are treatment options with proven clinical benefits as second-line therapy for mCRPC.[12],[13] Common toxicities encountered with cabazitaxel include neutropenia (82% grade ≥3), febrile neutropenia (8%), and anemia (11% grade ≥3).[7] On the other hand, abiraterone-related toxicities are fluid retention and edema (31% all grades, <3% grade ≥3) and hypokalemia (17% all grades, <4% grade ≥3).[14] Ours is the first report indicating the possibility that these two agents are equally potent in the second line setting. Due to the retrospective nature of our study, we could not compare toxicities associated with these two treatments. Our group is planning to prospectively compare quality of life as well as toxicities in the second line setting in patients with mCRPC.

In conclusion, this study has shown that abiraterone acetate is an effective agent for use in different lines of treatment in mCRPC. Further studies are needed to better address mCRPC patients so as to achieve greater benefit with each of these drugs.

 
 » References Top

1.
Siegel R., Naishadham D. and Jemal A. Cancer Statistics, 2013; CA Cancer J Clin 2013: 63: 11-30.  Back to cited text no. 1
    
2.
Sternberg CN, Petrylak DP, Sartor O, Witjes JA, Demkow T, Ferrero JM, et al. Multinational, double-blind, phase III study of prednisone and either satraplatin or placebo in patients with castrate-refractory prostate cancer progressing after prior chemotherapy: The SPARC trial. J Clin Oncol 2009;27:5431-8.  Back to cited text no. 2
    
3.
Pinto A. Beyond abiraterone: New hormonal therapies for metastatic castration-resistant prostate cancer Cancer Biol Ther. 2013 Oct 7;15 (2).  Back to cited text no. 3
    
4.
Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368 (2):138-48.  Back to cited text no. 4
    
5.
Molina A, Belldegrun A. Novel therapeutic strategies for castration resistant prostate cancer: Inhibition of persistent androgen production and androgen receptor mediated signaling. J Urol 2011;185:787-94.  Back to cited text no. 5
    
6.
Montgomery RB, Mostaghel EA, Vessella R, Hess DL, Kalhorn TF, Higano CS, et al. Maintenance of intratumoral androgens in metastatic prostate cancer: A mechanism for castration-resistant tumor growth. Cancer Res 2008;68:4447- 54.  Back to cited text no. 6
    
7.
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.  Back to cited text no. 7
[PUBMED]    
8.
Rathkopf DE, Smith MR, De Bono JS, Logothetis CJ, Shore ND, de SouzaP et al. Long-term safety and efficacy analysis of abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer without prior chemotherapy (COU-AA-302). J Clin Oncol 2013; 31:15. [ASCO Annual Meeting Abstracts].  Back to cited text no. 8
    
9.
De Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: A randomised open-label trial. Lancet 2010; 376:1147-54.  Back to cited text no. 9
    
10.
Sathiakumar N, Delzell E, Morrisey MA, Falkson C, Yong M, Chia V, et al. Mortality following bone metastasis and skeletal-related events among men with prostate cancer: A population-based analysis of US Medicare benefi ciaries, 1999-2006. Prostate Cancer Prostatic Dis 2011; 14:177-83.  Back to cited text no. 10
    
11.
Logothetis CJ, Basch E, Molina A, Fizazi K, North SA, Chi KN, et al. Effect of abiraterone acetate and prednisone compared with placebo and prednisone on pain control and skeletal-related events in patients with metastatic castration-resistant prostate cancer: Exploratory analysis of data from the COU-AA-301 randomised trial. Lancet Oncol. 2012 Dec; 13 (12):1210-7.  Back to cited text no. 11
    
12.
Garcia JA, Rini BI. Castration-resistant prostate cancer: Many treatments, many options, many challenges ahead. Cancer. 2012 May 15;118 (10):2583-93.  Back to cited text no. 12
    
13.
L. Albiges, S. Le Moulec, Y. Loriot, et al. Reponse to cabazitaxel in the postchemotherapy setting in CRPC patients previously treated with docetaxel and abiraterone acetate Annals of Oncology 2012; 23 (Supplement 9): ix294-ix318.  Back to cited text no. 13
    
14.
Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ, et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: Final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol 2012; 13:983-92.  Back to cited text no. 14
[PUBMED]    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1]

This article has been cited by
1 Sequencing Treatment for Castration-Resistant Prostate Cancer
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Current Treatment Options in Oncology. 2016; 17(12)
[Pubmed] | [DOI]



 

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