Low dose of interferon‑α improves the clinical outcomes of docetaxel in patients with castration‑resistant prostate cancer: A pilot study

Li,Yun‑Fei; Wang,Qin‑Zhang; Zhang,Tao‑Tao; Li,Lei; Wang,Jiang‑Ping; Ding,Guo‑Fu; He,Da‑Lin

doi:10.3892/ol.2013.1653

Low dose of interferon‑α improves the clinical outcomes of docetaxel in patients with castration‑resistant prostate cancer: A pilot study

Authors:
- Yun‑Fei Li
- Qin‑Zhang Wang
- Tao‑Tao Zhang
- Lei Li
- Jiang‑Ping Wang
- Guo‑Fu Ding
- Da‑Lin He
View Affiliations

Affiliations: Department of Urology, First Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China , Department of Urology, First Hospital of Shihezi University, Shihezi, Xinjiang 832008, P.R. China
Published online on: November 1, 2013 https://doi.org/10.3892/ol.2013.1653
Pages: 125-130

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of this study was to test whether a low dose of interferon‑α‑2b (IFN‑α2b) enhances the clinical outcome of docetaxel (DXT) in patients with castration‑resistant prostate cancer (CRPC). A prospective controlled trial of 40 CRPC patients receiving 5 mg of prednisone twice daily was conducted, where patients were randomly assigned to be administered 75 mg/m2 DXT plus 3 mIU/m2 IFN‑α2b (group A, n=20) or 75 mg/m2 DXT alone (group B, n=20). The prostate‑specific antigen (PSA) response, tumor response, progression‑free survival (PFS) and overall survival (OS) were evaluated. There was no statistically significant difference in PSA response rate between groups A and B (65 vs. 47.4%, P=0.341). The tumor response rate in group A was significantly greater compared with that in group B (55 vs. 21.1%, P=0.048). The median PFS was longer in group A compared with that in group B (10 vs. 8 months, P=0.043). There was no statistically significant difference in median OS between the two groups (19 vs. 17 months, P=0.348), but one patient displayed a complete tumor response in group A. In groups A and B, transient grade 3 to 4 neutropenia was observed in nine and six patients, grade 3 to 4 anemia was observed in three and five patients, and grade 3 to 4 general fatigue was observed in four and one patient(s), respectively. The proportion of patients with grade 3 to 4 toxicity was not statistically different between the two groups. A low dosage of IFN‑α2b may improve the antitumor activity of DXT with an acceptable toxicity profile in patients with CRPC.

View Figures

View References

1	Feldman BJ and Feldman D: The development of androgen-independent prostate cancer. Nat Rev Cancer. 1:34–45. 2001. View Article : Google Scholar : PubMed/NCBI
2	Pienta KJ and Bradley D: Mechanisms underlying the development of androgen-independent prostate cancer. Clin Cancer Res. 12:1665–1671. 2006. View Article : Google Scholar : PubMed/NCBI
3	Tannock IF, de Wit R, Berry WR, et al: Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 351:1502–1512. 2004. View Article : Google Scholar : PubMed/NCBI
4	Berthold DR, Pond GR, Soban F, de Wit R, Eisenberger M and Tannock IF: Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. J Clin Oncol. 26:242–245. 2008. View Article : Google Scholar : PubMed/NCBI
5	Makarovskiy AN, Siryaporn E, Hixson DC and Akerley W: Survival of docetaxel-resistant prostate cancer cells in vitro depends on phenotype alterations and continuity of drug exposure. Cell Mol Life Sci. 59:1198–1211. 2002. View Article : Google Scholar
6	McDonnell TJ, Troncoso P, Brisbay SM, et al: Expression of the protooncogene bcl-2 in the prostate and its association with emergence of androgen-independent prostate cancer. Cancer Res. 52:6940–6944. 1992.PubMed/NCBI
7	Banerjee PP, Banerjee S and Brown TR: Bcl-2 protein expression correlates with cell survival and androgen independence in rat prostatic lobes. Endocrinology. 143:1825–1832. 2002. View Article : Google Scholar : PubMed/NCBI
8	Ventura A, Kirsch DG, McLaughlin ME, et al: Restoration of p53 function leads to tumour regression in vivo. Nature. 445:661–665. 2007. View Article : Google Scholar : PubMed/NCBI
9	Leprince D, Crepieux P, Laudet V, Flourens A and Stehelin D: A new mechanism of oncogenic activation: E26 retroviral v-ets oncogene has inverted the C-terminal end of the transcription factor c-ets-1. Virology. 194:855–857. 1993. View Article : Google Scholar : PubMed/NCBI
10	Liu C, Zhu Y, Lou W, et al: Functional p53 determines docetaxel sensitivity in prostate cancer cells. Prostate. 73:418–427. 2013. View Article : Google Scholar : PubMed/NCBI
11	Panaretakis T, Pokrovskaja K, Shoshan MC and Grander D: Interferon-alpha-induced apoptosis in U266 cells is associated with activation of the proapoptotic Bcl-2 family members Bak and Bax. Oncogene. 22:4543–4556. 2003. View Article : Google Scholar : PubMed/NCBI
12	Davol PA, Goulette FA, Frackelton AR Jr and Darnowski JW: Modulation of p53 expression by human recombinant interferon-alpha2a correlates with abrogation of cisplatin resistance in a human melanoma cell line. Cancer Res. 56:2522–2526. 1996.PubMed/NCBI
13	Huang SF, Kim SJ, Lee AT, et al: Inhibition of growth and metastasis of orthotopic human prostate cancer in athymic mice by combination therapy with pegylated interferon-alpha-2b and docetaxel. Cancer Res. 62:5720–5726. 2002.
14	Emerson L and Morales A: Intralesional recombinant alpha-interferon for localized prostate cancer: a pilot study with follow-up of >10 years. BJU Int. 104:1068–1070. 2009.
15	Shinohara N, Abe T, Sazawa A, et al: Interferon-α-based immunotherapy in metastatic renal cell carcinoma patients with the primary tumor in situ. Jpn J Clin Oncol. 42:113–119. 2012.
16	Mocellin S, Pasquali S, Rossi CR and Nitti D: Interferon alpha adjuvant therapy in patients with high-risk melanoma: a systematic review and meta-analysis. J Natl Cancer Inst. 102:493–501. 2010. View Article : Google Scholar : PubMed/NCBI
17	van Haelst-Pisani CM, Richardson RL, Su J, et al: A phase II study of recombinant human alpha-interferon in advanced hormone-refractory prostate cancer. Cancer. 70:2310–2312. 1992.PubMed/NCBI
18	Bulbul MA, Huben RP and Murphy GP: Interferon-beta treatment of metastatic prostate cancer. J Surg Oncol. 33:231–233. 1986. View Article : Google Scholar : PubMed/NCBI
19	Padhani AR and Ollivier L: The RECIST (Response Evaluation Criteria in Solid Tumors) criteria: implications for diagnostic radiologists. Br J Radiol. 74:983–986. 2001. View Article : Google Scholar : PubMed/NCBI
20	DiPaola RS, Chen YH, Stein M, et al: A randomized phase II trial of mitoxantrone, estramustine and vinorelbine or bcl-2 modulation with 13-cis retinoic acid, interferon and paclitaxel in patients with metastatic castrate-resistant prostate cancer: ECOG 3899. J Transl Med. 8:202010. View Article : Google Scholar
21	Anatol P, Danuta P, Janusz D and Bozena P: Expression of bcl-2 protein in chronic hepatitis C: effect of interferon alpha 2b with ribavirin therapy. World J Gastroenterol. 11:2949–2952. 2005. View Article : Google Scholar : PubMed/NCBI
22	Amato RJ and Mohammad T: Interferon-alpha plus capecitabine and thalidomide in patients with metastatic renal cell cancer. J Exp Ther Oncol. 7:41–47. 2008.
23	Rosevear HM, Lightfoot AJ, Nepple KG and O’Donnell MA: Usefulness of the Spanish Urological Club for Oncological Treatment scoring model to predict nonmuscle invasive bladder cancer recurrence in patients treated with intravesical bacillus Calmette-Guérin plus interferon-α. J Urol. 185:67–71. 2011.
24	Panasiuk A, Prokopowicz D and Dzieciol J: p53 protein expression in chronic hepatitis C; effect of interferon alpha 2b therapy. Hepatogastroenterology. 52:1176–1179. 2005.PubMed/NCBI
25	Kelly WK, Halabi S, Carducci M, et al: Randomized, double-blind, placebo-controlled phase III trial comparing docetaxel and prednisone with or without bevacizumab in men with metastatic castration-resistant prostate cancer: CALGB 90401. J Clin Oncol. 30:1534–1540. 2012. View Article : Google Scholar
26	Koirala J, Gandotra SD, Rao S, et al: Granulocyte colony-stimulating factor dosing in pegylated interferon alpha-induced neutropenia and its impact on outcome of anti-HCV therapy. J Viral Hepat. 14:782–787. 2007. View Article : Google Scholar
27	Chang AY, Fisher HA, Spiers AS and Boros L: Toxicities of human recombinant interferon-alpha 2 in patients with advanced prostate carcinoma. J Interferon Res. 6:713–715. 1986. View Article : Google Scholar : PubMed/NCBI
28	ten Tije AJ, Verweij J, Carducci MA, et al: Prospective evaluation of the pharmacokinetics and toxicity profile of docetaxel in the elderly. J Clin Oncol. 23:1070–1077. 2005.PubMed/NCBI