Skip to main content

Clinical Management of Elderly Patients with Metastatic Prostate Cancer Chemotherapy

  • Chapter
  • First Online:
Management of Urological Cancers in Older People

Part of the book series: Management of Cancer in Older People ((volume 1))

  • 696 Accesses

Abstract

Docetaxel and cabazitaxel chemotherapy have modestly extended survival as first- or second-line chemotherapy for patients with metastatic castration-resistant prostate cancer. Mitoxantrone chemotherapy may continue to play a palliative role in selected patients. In general, elderly age alone does not preclude chemotherapy or other therapies in patients that qualify based on a satisfactory biologic age, i.e., with no serious uncontrolled comorbidities, ECOG performance status 0–2, adequate organ and cognitive function, and satisfactory nutritional status and social support. Despite trends for increasing toxicities, selected elderly patients appear to generally tolerate chemotherapy and derive benefits similar to their younger counterparts. However, given the increased prevalence of comorbidities, functional impairments, and organ dysfunctions in the elderly, careful selection of patients coupled with dose modifications and prophylactic measures to avoid toxicities is necessary. Trials are also investigating the role of docetaxel for earlier stages of prostate cancer and comparing docetaxel with cabazitaxel as first-line chemotherapy. In the context of an increasing pipeline of novel approved agents (abiraterone acetate, sipuleucel-T) and emerging agents (radium-223, MDV-3100), optimal survival will probably be realized by the sequential utilization of several different classes of agents.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 229.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. de Bono JS, Oudard S, Ozguroglu M, 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(9747):1147–54.

    Article  PubMed  Google Scholar 

  2. Mohile SG, Xian Y, Dale W, et al. Association of a cancer diagnosis with vulnerability and frailty in older Medicare beneficiaries. J Natl Cancer Inst. 2009;101(17):1206–15.

    Article  PubMed  Google Scholar 

  3. Extermann M, Hurria A. Comprehensive geriatric assessment for older patients with cancer. J Clin Oncol. 2007;25(14):1824–31.

    Article  PubMed  Google Scholar 

  4. Balducci L, Extermann M. Management of the frail person with advanced cancer. Crit Rev Oncol Hematol. 2000;33(2):143–8.

    Article  PubMed  CAS  Google Scholar 

  5. Min LC, Elliott MN, Wenger NS, Saliba D. Higher vulnerable elders survey scores predict death and functional decline in vulnerable older people. J Am Geriatr Soc. 2006;54(3):507–11.

    Article  PubMed  Google Scholar 

  6. Hurria A, Cirrincione CT, Muss HB, et al. Implementing a geriatric assessment in cooperative group clinical cancer trials: CALGB 360401. J Clin Oncol. 2011;29(10):1290–6.

    Article  PubMed  Google Scholar 

  7. Read WL, Tierney RM, Page NC, et al. Differential prognostic impact of comorbidity. J Clin Oncol. 2004;22(15):3099–103.

    Article  PubMed  Google Scholar 

  8. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.

    Article  PubMed  CAS  Google Scholar 

  9. Piccirillo JF, Tierney RM, Costas I, Grove L, Spitznagel Jr EL. Prognostic importance of comorbidity in a hospital-based cancer registry. JAMA. 2004;291(20):2441–7.

    Article  PubMed  CAS  Google Scholar 

  10. Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351(15):1502–12.

    Article  PubMed  CAS  Google Scholar 

  11. Petrylak DP, Tangen CM, Hussain MH, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004;351(15):1513–20.

    Article  PubMed  CAS  Google Scholar 

  12. Berthold DR, Pond GR, Soban F, de Wit R, Eisenberger M, Tannock IF. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. J Clin Oncol. 2008;26(2):242–5.

    Article  PubMed  CAS  Google Scholar 

  13. Berthold DR, Pond GR, Roessner M, de Wit R, Eisenberger M, Tannock AI. Treatment of hormone-refractory prostate cancer with docetaxel or mitoxantrone: relationships between prostate-specific antigen, pain, and quality of life response and survival in the TAX-327 study. Clin Cancer Res. 2008;14(9):2763–7.

    Article  PubMed  CAS  Google Scholar 

  14. Fizazi K, Le Maitre A, Hudes G, et al. Addition of estramustine to chemotherapy and survival of patients with castration-refractory prostate cancer: a meta-analysis of individual patient data. Lancet Oncol. 2007;8(11):994–1000.

    Article  PubMed  CAS  Google Scholar 

  15. Lubiniecki GM, Berlin JA, Weinstein RB, Vaughn DJ. Thromboembolic events with estramustine phosphate-based chemotherapy in patients with hormone-refractory prostate carcinoma: results of a meta-analysis. Cancer. 2004;101(12):2755–9.

    Article  PubMed  CAS  Google Scholar 

  16. Cell Genesys Halts VITAL-2 GVAX trial in advanced prostate cancer. 2010. http://phx.corporate-ir.net/phoenix.zhtml?c=98399&p=irol-newsArticle&ID=1191052. Accessed 3 Jan 2010.

  17. Scher HI, Jia X, Chi K, et al. Randomized, open-label phase III trial of docetaxel plus high-dose calcitriol versus docetaxel plus prednisone for patients with castration-resistant prostate cancer. J Clin Oncol. 2011;29(16):2191–8.

    Article  PubMed  CAS  Google Scholar 

  18. Tannock IF, Osoba D, Stockler MR, et al. Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points. J Clin Oncol. 1996;14(6):1756–64.

    PubMed  CAS  Google Scholar 

  19. Beer TM, Ryan CW, Venner PM, et al. Intermittent chemotherapy in patients with metastatic androgen-independent prostate cancer: results from ASCENT, a double-blinded, randomized comparison of high-dose calcitriol plus docetaxel with placebo plus docetaxel. Cancer. 2008;112(2):326–30.

    Article  PubMed  CAS  Google Scholar 

  20. Loriot Y, Massard C, Gross-Goupil M, et al. The interval from the last cycle of docetaxel-based chemotherapy to progression is associated with the efficacy of subsequent docetaxel in patients with prostate cancer. Eur J Cancer. 2010;46(10):1770–2.

    Article  PubMed  CAS  Google Scholar 

  21. Pond GR, Armstrong AJ, Wood BA, et al. Evaluating the value of number of cycles of docetaxel and prednisone in men with metastatic castration-resistant prostate cancer. Eur Urol. 2012;61:363–9.

    Article  PubMed  CAS  Google Scholar 

  22. Franke RM, Carducci MA, Rudek MA, Baker SD, Sparreboom A. Castration-dependent pharmacokinetics of docetaxel in patients with prostate cancer. J Clin Oncol. 2010;28(30):4562–7.

    Article  PubMed  CAS  Google Scholar 

  23. Berthold DR, Pond GR, de Wit R, Eisenberger M, Tannock IF. Survival and PSA response of patients in the TAX 327 study who crossed over to receive docetaxel after mitoxantrone or vice versa. Ann Oncol. 2008;19(10):1749–53.

    Article  PubMed  CAS  Google Scholar 

  24. Rosenberg JE, Galsky MD, Rohs NC, et al. A retrospective evaluation of second-line chemotherapy response in hormone-refractory prostate carcinoma: second line taxane-based therapy after first-line epothilone-B analog ixabepilone (BMS-247550) therapy. Cancer. 2006;106(1):58–62.

    Article  PubMed  CAS  Google Scholar 

  25. Takaha N, Okihara K, Kamoi K, et al. Feasibility of tri-weekly docetaxel-based chemotherapy for elderly patients (age 75 and older) with castration-resistant prostate cancer. Urol Int. 2011;87(3):263–9.

    Article  PubMed  CAS  Google Scholar 

  26. Halabi S, Kelly WK, George DJ, et al. Comorbidities predict overall survival (OS) in men with metastatic castrate-resistant prostate cancer (CRPC). J Clin Oncol. 2011;9 (suppl 7; abstr 189).

    Google Scholar 

  27. Kelly W, Halabi S, Carducci MA, et al. A randomized, double-blind, placebo-controlled phase III trial comparing docetaxel, prednisone, and placebo with docetaxel, prednisone, and bevacizumab in men with metastatic castration-resistant prostate cancer (mCRPC): survival results of CALGB 90401. J Clin Oncol. 2010;28:18s (suppl; abstr LBA4511).

    Google Scholar 

  28. Halabi S, Small EJ, Kantoff PW, et al. Prognostic model for predicting survival in men with hormone-refractory metastatic prostate cancer. J Clin Oncol. 2003;21(7):1232–7.

    Article  PubMed  Google Scholar 

  29. de Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364(21):1995–2005.

    Article  PubMed  Google Scholar 

  30. Kantoff PW, Halabi S, Conaway M, et al. Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the cancer and leukemia group B 9182 study. J Clin Oncol. 1999;17(8):2506–13.

    PubMed  CAS  Google Scholar 

  31. Rosenberg JE, Weinberg VK, Kelly WK, et al. Activity of second-line chemotherapy in docetaxel-refractory hormone-refractory prostate cancer patients: randomized phase 2 study of ixabepilone or mitoxantrone and prednisone. Cancer. 2007;110(3):556–63.

    Article  PubMed  CAS  Google Scholar 

  32. Sternberg CN, Petrylak DP, Sartor O, 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(32):5431–8.

    Article  PubMed  CAS  Google Scholar 

  33. Ross RW, Beer TM, Jacobus S, et al. A phase 2 study of carboplatin plus docetaxel in men with metastatic hormone-refractory prostate cancer who are refractory to docetaxel. Cancer. 2008;112(3):521–6.

    Article  PubMed  CAS  Google Scholar 

  34. Hussain M, Tangen CM, Lara Jr PN, et al. Ixabepilone (epothilone B analogue BMS-247550) is active in chemotherapy-naive patients with hormone-refractory prostate cancer: a Southwest Oncology Group trial S0111. J Clin Oncol. 2005;23(34):8724–9.

    Article  PubMed  Google Scholar 

  35. Galsky MD, Small EJ, Oh WK, et al. Multi-institutional randomized phase II trial of the epothilone B analog ixabepilone (BMS-247550) with or without estramustine phosphate in patients with progressive castrate metastatic prostate cancer. J Clin Oncol. 2005;23(7):1439–46.

    Article  PubMed  CAS  Google Scholar 

  36. Harzstark AL, Rosenberg JE, Weinberg VK, et al. Ixabepilone, mitoxantrone, and prednisone for metastatic castration-resistant prostate cancer after docetaxel-based therapy: a phase 2 study of the department of defense prostate cancer clinical trials consortium. Cancer. 2010 December 29 [Epub ahead of print].

    Google Scholar 

  37. Chi KN, Beardsley E, Eigl BJ, et al. A phase 2 study of patupilone in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel: Canadian Urologic Oncology Group study P07a. Ann Oncol. 2012;23:53–8.

    Article  PubMed  CAS  Google Scholar 

  38. Beer TM, Smith D, Hussain M, et al. Phase II study of first-line sagopilone combined with prednisone in patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2009;27:15s (suppl; abstr 5059).

    Article  Google Scholar 

  39. de Bono JS, Molife LR, Sonpavde G, et al. Phase II study of eribulin mesylate (E7389) in patients with metastatic castration-resistant prostate cancer stratified by prior taxane therapy. Ann Oncol. 2012;23:1241–9.

    Article  PubMed  Google Scholar 

  40. Papandreou CN, Daliani DD, Thall PF, et al. Results of a phase II study with doxorubicin, etoposide, and cisplatin in patients with fully characterized small-cell carcinoma of the prostate. J Clin Oncol. 2002;20(14):3072–80.

    Article  PubMed  CAS  Google Scholar 

  41. Hurria A, Togawa K, Mohile SG, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol. 2011;29(25):3457–65.

    Article  PubMed  CAS  Google Scholar 

  42. Frasci G, Lorusso V, Panza N, et al. Gemcitabine plus vinorelbine versus vinorelbine alone in elderly patients with advanced non-small-cell lung cancer. J Clin Oncol. 2000;18(13):2529–36.

    PubMed  CAS  Google Scholar 

  43. Extermann M, Boler I, Reich RR, et al. Predicting the risk of chemotherapy toxicity in older patients: the chemotherapy risk assessment scale for high-age patients (CRASH) score. ;Cancer. doi:10.1002/cncr.26646.

  44. Lyman GH, Kuderer NM, Crawford J, et al. Predicting individual risk of neutropenic complications in patients receiving cancer chemotherapy. Cancer. 2011;117(9):1917–27.

    Article  PubMed  Google Scholar 

  45. Prado CM, Baracos VE, McCargar LJ, et al. Sarcopenia as a determinant of chemotherapy toxicity and time to tumor progression in metastatic breast cancer patients receiving capecitabine treatment. Clin Cancer Res. 2009;15(8):2920–6.

    Article  PubMed  CAS  Google Scholar 

  46. Herbst C, Naumann F, Kruse EB, et al. Prophylactic antibiotics or G-CSF for the prevention of infections and improvement of survival in cancer patients undergoing chemotherapy. Cochrane Database Syst Rev. 2009;1:CD007107.

    PubMed  Google Scholar 

  47. Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363(5):411–22.

    Article  PubMed  CAS  Google Scholar 

  48. Mohile SG, Fan L, Reeve E, et al. Association of cancer with geriatric syndromes in older Medicare beneficiaries. J Clin Oncol. 2011;29(11):1458–64.

    Article  PubMed  Google Scholar 

  49. Fizazi K, Carducci M, Smith M, et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet. 2011;377(9768):813–22.

    Article  PubMed  CAS  Google Scholar 

  50. Scher HI, Halabi S, Tannock I, et al. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 2008;26(7):1148–59.

    Article  PubMed  Google Scholar 

  51. Armstrong AJ, Garrett-Mayer ES, Yang YC, de Wit R, Tannock IF, Eisenberger M. A contemporary prognostic nomogram for men with hormone-refractory metastatic prostate cancer: a TAX327 study analysis. Clin Cancer Res. 2007;13(21):6396–403.

    Article  PubMed  CAS  Google Scholar 

  52. Armstrong AJ, Tannock IF, de Wit R, George DJ, Eisenberger M, Halabi S. The development of risk groups in men with metastatic castration-resistant prostate cancer based on risk factors for PSA decline and survival. Eur J Cancer. 2010;46(3):517–25.

    Article  PubMed  CAS  Google Scholar 

  53. Armstrong AJ, Garrett-Mayer E, de Wit R, Tannock I, Eisenberger M. Prediction of survival following first-line chemotherapy in men with castration-resistant metastatic prostate cancer. Clin Cancer Res. 2010;16(1):203–11.

    Article  PubMed  CAS  Google Scholar 

  54. Petrylak DP, Ankerst DP, Jiang CS, et al. Evaluation of prostate-specific antigen declines for surrogacy in patients treated on SWOG 99–16. J Natl Cancer Inst. 2006;98(8):516–21.

    Article  PubMed  Google Scholar 

  55. Armstrong AJ, Garrett-Mayer E, Ou Yang YC, et al. Prostate-specific antigen and pain surrogacy analysis in metastatic hormone-refractory prostate cancer. J Clin Oncol. 2007;25(25):3965–70.

    Article  PubMed  Google Scholar 

  56. Hussain M, Goldman B, Tangen C, et al. Prostate-specific antigen progression predicts overall survival in patients with metastatic prostate cancer: data from Southwest Oncology Group Trials 9346 (Intergroup Study 0162) and 9916. J Clin Oncol. 2009;27(15):2450–6.

    Article  PubMed  Google Scholar 

  57. Halabi S, Vogelzang NJ, Ou SS, Owzar K, Archer L, Small EJ. Progression-free survival as a predictor of overall survival in men with castrate-resistant prostate cancer. J Clin Oncol. 2009;27(17):2766–71.

    Article  PubMed  Google Scholar 

  58. Sonpavde G, Pond GR, Berry WR, et al. The association between radiographic response and overall survival in men with metastatic castration-resistant prostate cancer receiving chemotherapy. Cancer. 2011;117:3963–71.

    Article  PubMed  Google Scholar 

  59. de Bono JS, Scher HI, Montgomery RB, et al. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res. 2008;14(19):6302–9.

    Article  PubMed  Google Scholar 

  60. Scher H HG, Molina A, Kheoh T, Attard G, Moreira J, Sandhu S, Parker C, Logothetis C, McCormack R, Fizazi K, Anand A, Danila D, Fleisher M, Olmos D, Haqq C, De Bono J. Evaluation of circulating tumor cell (CTC) enumeration as an efficacy response biomarker of overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC): planned final analysis (FA) of COU-AA-301, a randomized double-blind, placebo-controlled phase III study of abiraterone acetate (AA) plus low-dose prednisone (P) post docetaxel. J Clin Oncol. 2011;29 (suppl; abstr LBA4517^).

    Google Scholar 

  61. Magi-Galluzzi C, Zhou M, Reuther AM, Dreicer R, Klein EA. Neoadjuvant docetaxel treatment for locally advanced prostate cancer: a clinicopathologic study. Cancer. 2007;110(6):1248–54.

    Article  PubMed  CAS  Google Scholar 

  62. Chi KN, Chin JL, Winquist E, Klotz L, Saad F, Gleave ME. Multicenter phase II study of combined neoadjuvant docetaxel and hormone therapy before radical prostatectomy for patients with high risk localized prostate cancer. J Urol. 2008;180(2):565–70; discussion 570.

    Article  PubMed  CAS  Google Scholar 

  63. Flaig TW, Tangen CM, Hussain MH, et al. Randomization reveals unexpected acute leukemias in Southwest Oncology Group prostate cancer trial. J Clin Oncol. 2008;26(9):1532–6.

    Article  PubMed  CAS  Google Scholar 

  64. Droz JP, Balducci L, Bolla M, et al. Management of prostate cancer in older men: recommendations of a working group of the International Society of Geriatric Oncology. BJU Int. 2010;106(4):462–9.

    Article  PubMed  Google Scholar 

  65. Kolevska T, Rayan C, Huey V, et al. Phase II trial of nab-paclitaxel as first-line therapy of hormone refractory metastatic prostate cancer. J Clin Oncol. 2009;27:15s (suppl; abstr 5152).

    Article  Google Scholar 

Download references

Grants, Research Support and Financial Disclosures

Guru Sonpavde, M.D., receives research support from Eli Lilly-Imclone, Pfizer, BMS, Novartis, Teva, Celgene, Cytogen and Astrazeneca and is on the speakers’ bureau or advisory board for Pfizer, Novartis, GSK, Dendreon, Amgen, Astellas and Sanofi-Aventis.

Cora N. Sternberg, M.D. has received research support from Sanofi-Aventis, Cougar Biotech, and Astellas.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Guru Sonpavde M.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag London

About this chapter

Cite this chapter

Sonpavde, G., Sternberg, C.N. (2013). Clinical Management of Elderly Patients with Metastatic Prostate Cancer Chemotherapy. In: Droz, JP., Audisio, R. (eds) Management of Urological Cancers in Older People. Management of Cancer in Older People, vol 1. Springer, London. https://doi.org/10.1007/978-0-85729-999-4_13

Download citation

  • DOI: https://doi.org/10.1007/978-0-85729-999-4_13

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-0-85729-986-4

  • Online ISBN: 978-0-85729-999-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics