Skip to main content
NCBI home page
Journal of Cancer Research and Clinical Oncology logoLink to Journal of Cancer Research and Clinical Oncology
. 1996 Mar;122(3):171–176. doi: 10.1007/BF01366958

Maximal androgen blockade in combination with methotrexate for treatment of metastatic prostate cancer

Peter Sagaster 1,✉, Johannes Flamm 2, Michael Micksche 3, Elke Fritz 1, Gerhard Donner 4, Heinz Ludwig 1
PMCID: PMC12201268  PMID: 8601566

Abstract

Recently attention has been focused on the optimal timing of chemotherapy within the treatment regimen for patients with metastatic prostate cancer, i.e., hormonal manipulation, preferably maximal androgen blockage (MAB) consisting of chemical/surgical castration followed by treatment with antiandrogens. We have conducted a randomized prospective clinical trial, investigating the efficacy and toxicity of MAB (orchiectomy followed by flutamide therapy) alone as compared to MAB combined with methotrexate (MTX, 50 mg/m2/week) in 53 patients with newly diagnosed stage IV (M1) prostatic cancer (UICC TNM Classification 1987). The observed remission rates (complete+partial) of 42.3% in the MAB+MTX arm and 29.6% in the MAB arm did not differ significantly. The response rates (complete+partial+stable disease) of 73.1% and 66.7% for MAB+MTX and MAB, respectively, also showed no significant difference. Neither progression-free survival (median: 18.5 and 23.8 months for MAB+MTX and MAB, respectively) nor overall survival (median: 37.4 and 36.1) months in the MAB+MTX and MAB arm, respectively) could be improved by the addition of MTX to MAB. Only the extent of metastatic pain reported by the patients was consistently less under MAB+MTX than under MAB alone (P<0.1). Both treatment regimens were well-tolerated with slightly more undesirable effects in the MAB+MTX arm. Our results do not provide evidence for the achievement of marked gains by combining chemotherapy with endocrine therapy in newly diagnosed patients with stage IV (M1) prostate cancer.

Key words: Prostate cancer, Maximal androgen blockade, Methotrexate, Randomized trial

Abbreviations

MAB

maximum androgen blockade

MTX

methotrexate

PSA

prostate-specific antigen

References

  1. Armitage P (1958) Sequential methods in clinical trials. Am J Public Health 48:1395–1402 [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Crawford ED, Eisenberger MA, McLeod DG, Spaulding, JT, Benson R, Dorr FA, Blumenstein BA, Davis MA, Goodman PJ (1989) A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. N Engl J Med 321:419–424 [DOI] [PubMed] [Google Scholar]
  3. Daneshgari F, Crawford ED (1993) Endocrine therapy of advanced carcinoma of the prostate. Cancer 71:1089–1097 [DOI] [PubMed] [Google Scholar]
  4. Goldrath DE, Messing EM (1989) Prostate specific antigen: not detectable despite tumor progression after radical prostatectomy. J Urol 142:1082–1084 [DOI] [PubMed] [Google Scholar]
  5. Huben RP, Murphy GP (1988) A comparison of diethylstilbestrol or orchiectomy with buserelin and with methotrexate plus diehtylstilbestrol or orchiectomy in newly diagnosed patients with clinical stage D2 cancer of the prostate. Cancer 62:1881–1887 [DOI] [PubMed] [Google Scholar]
  6. Huggins C, Hodges CV (1972) Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. CA 22:232–240 [DOI] [PubMed] [Google Scholar]
  7. Isaacs JT (1984) The timing of androgen ablation therapy and/or chemotherapy in the tretment of prostatic cancer. Prostate 5:1–17 [DOI] [PubMed] [Google Scholar]
  8. Janknegt RA, Abbou CC, Bartoletti R, Bernstein-Hahl L, Bracken B, Brisset JM, Calais Da Silva F, Chisholm G, Crawford ED, Debruyne J, Dijkman GD, Frick J, Goedhals L, Knoenagel H, Venner PM (1993) Orchiectomy and nilutamide or placebo as treatment of metastatic prostatic cancer in a multinational double-blind randomized trial. J Urol 149:77–82 [DOI] [PubMed] [Google Scholar]
  9. Koutsilieris M, Faure N, Tolis G, Laroche B, Robert G, Ackman CF (1986) Objective response and disease outcome in 59 patients with stage D2 prostatic cancer treated with either Buserelin or orchiectomy. Disease aggressivity and its association with response and outcome. Urology 27:221–228 [DOI] [PubMed] [Google Scholar]
  10. Labrie F, Dupont A, Belanger A, Cusan L, Lacourciere Y, Monfette G, Laberge JG, Edmond JP, Fazekas ATA, Raynaud JP, Husson JM (1982) New hormonal therapy in prostatic carcinoma: combined treatment with an LHRH agonist and an antiandrogen. Clin Invest Med 5:267–275 [PubMed] [Google Scholar]
  11. Loening SA, Beckley S, Brady MF, Chu TM, deKernion JB, Dhabuwala C, Gaeta JF, Gibbons RP, Mc Kiel CF, Mc Leot DG, Pontes JE, Prout GR, Cardino PT, Schlegel JU, Schmidt JD, Scott WW, Slcak NH (1983) Comparison of estramustine phosphate, methotrexate and cis-platinum in patients with advanced, hormone refractory prostate cancer. J Urol 129:1001–1006 [DOI] [PubMed] [Google Scholar]
  12. Murphy GP, Beckley S, Brady MF, Chu TM, deKernion HB, Dhabuwala C, Gaeta JF, Gibbons RP, Loening SA, McKiel CF, McLeod DG, Pontes JE, Prout GR, Scardino IE, Schlegel JU, Schmidt JD, Scott WW, Slack NH, Soloway MS (1983) Treatment of newly diagnosed metastatic prostate cancer patients with chemotherapy agents in combinations with hormones versus hormones alone. Cancer 51:1264–1272 [DOI] [PubMed] [Google Scholar]
  13. Murphy GP, Huben RP, Priore R (1986) Results of another trial of chemotherapy with and without hormones in patients with newly diagnosed metastatic prostate cancer. Urology 28:36–40 [DOI] [PubMed] [Google Scholar]
  14. Osborne CK, Blumenstein B, Crawford ED, Coltman CA Jr, Smith AY, Lambuth BW, Chapman RA (1990) Combined versus sequential chemo-endocrine therapy in advanced prostate cancer: final results of a randomized Southwest Oncology Group study. J Clin Oncol 8:1675–1682 [DOI] [PubMed] [Google Scholar]
  15. Van Popel H, van den Broucke F, Derluyn J, Popelier G, Casselman J, Billiet I, van Uytsel L, Paridaens R, Baert L (1993) Mitomycin C in combination with orchiectomy for newly diagnosed metastatic prostate cancer: preliminary results on a randomized trial. J Urol 149:1485–1487 [DOI] [PubMed] [Google Scholar]
  16. UICC (1987) TNM-Klassifikation maligner Tumoren. Hermanek P, Scheibe O, Spiessl B, Wagner G (eds) International Union Against Cancer (UICC). Springer, Berlin Heidelberg New York [Google Scholar]
  17. WHO (1979) Handbook for Reporting Results of Cancer Treatment. WHO Offset Publ, 48
  18. Yagoda A, Petrylak D (1993) Cytotoxic chemotherapy for advanced hormone-resistant prostate cancer. Cancer 71:1098–1109 [DOI] [PubMed] [Google Scholar]

Articles from Journal of Cancer Research and Clinical Oncology are provided here courtesy of Springer

RESOURCES