|Year : 2015 | Volume
| Issue : 4 | Page : 658-660
Line of abiraterone acetate in castration-resistant metastatic prostate cancer - Does it matter? report of a multi-institutional experience
S Gunduz1, H Bozcuk1, M Yıldız2, SS Goksu1, M Uysal3, D Arslan1, AM Tatlı1, H Mutlu1, HS Coşkun1, M Ozdogan4
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 Publication||10-Mar-2016|
Department of Medical Oncology, Akdeniz University Hospital, Antalya
Source of Support: None, Conflict of Interest: None
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 13];52:658-60. Available from: http://www.indianjcancer.com/text.asp?2015/52/4/658/178379
| » Introduction|| |
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. 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.
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.,,,,, 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|| |
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.
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|| |
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].
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%.
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).
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|| |
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).
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.,
Both abiraterone and cabazitaxel are treatment options with proven clinical benefits as second-line therapy for mCRPC., Common toxicities encountered with cabazitaxel include neutropenia (82% grade ≥3), febrile neutropenia (8%), and anemia (11% grade ≥3). 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). 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.
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[Figure 1], [Figure 2], [Figure 3]
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|[Pubmed] | [DOI]|