Advertisement

Cancer Chemotherapy and Pharmacology

, Volume 18, Supplement 2, pp S45–S50 | Cite as

VP 16 plus ifosfamide plus cisplatin as salvage therapy in refractory testicular cancer

  • Lawrence H. Einhorn
International Satellite Symposium to the 3rd European Conference on Clinical Oncology Stockholm, June 1985 Recent Experience with Ifosfamide/Mesna in Solid Tumor VP 16, Ifosfamide, Cisplatin, Testicular Cancer

Summary

In patients with refractory germ cell tumour who fail to achieve complete remission (CR) or which achieve CR but subsequently experience disease progression within 2 months of receiving cisplatin + vinblastine + bleomycin (PVB) the results of further treatment are poor. Similarly, third-line therapy after cisplatin with VP 16 salvage rarely produces clinically significant remission. From February 1983 to October 1984 we treated 53 patients with ifosfamide (1.2 g/m2 per day on days 1–5), VP 16 (75 mg/m2 per day on days 1–5), cisplatin (20 mg/m2 per day on days 1–5), andN-acetylcysteine (2.0 g p.o. every 6 h on days 1–7). This was repeated every 21 days for four to six cycles. One group of patients (group A, 20 pts) had achieved partial remission (PR) but still had nonresectable tumours after PVB therapy; a further group (group B, 4 pts) had achieved CR with PVB but then experienced disease progression within 2 months; the remaining patients (group C, 28 pts) had experienced disease progression after one or more salvage attempts, including therapy with cisplatin and VP 16. Of the original 53 patients, 51 were evaluable for response. Toxicity included moderate to severe myelosuppression in almost all patients, fever/sepsis in 8, creatinine ≥6 mg% in 4, and hematuria in 4 patients. There were no drug-related deaths. CR was attained in 17/51 patients (34%), these being 8/20 in group A, 1/4 in group B, and 8/28 in group C, and 10 patients have remained in CR for periods ranging from over 1 month to over 17 months. PR was achieved in 20 patients (40%), but their median duration of remission was only 2 months. We feel these results, obtained in a poorprognosis patient population, are sufficiently encouraging to warrant further study of this regimen, including investigation of its use as initial salvage therapy following PVB.

Keywords

Germ Cell Complete Remission Bleomycin Ifosfamide Germ Cell Tumour 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Aiginger P, Schwartz HP, Kuzmits R, Frass M, Kühböck (1982) Ifosfamide and cisplatinum in testicular tumor patients resistant to vinblastine, bleomycin, cisplatinum. Proc 13th Int Cancer Congress 13:180Google Scholar
  2. 2.
    Blijham G, Spitzer G, Litam J, Zander AR, Verma DS, Vellekoop L, Samuels ML, McGredie KB, Dicke KA (1981) The treatment of advanced testicular carcinoma with high-dose chemotherapy and autologous marrow support. Eur J Cancer 17:433–441Google Scholar
  3. 3.
    Bosl GJ, Yagoda A, Whitmore WF, et al. (1984) VP-16-213 and cisplatin in the treatment of patients with refractory germ cell tumors. Am J Clin Oncol 7:327–30Google Scholar
  4. 4.
    Boutis LL, Stergiou-Tavantzis J, Mouratidou D, et al. (1982) Ifosfamide chemotherapy of disseminated non-seminomatous testicular cancer. (Abstract). Proc 13th Int Cancer Congress 13:181Google Scholar
  5. 5.
    Bremer K, Niederle N, Krischke W, et al. (1982) Etoposide and etoposide-ifosfamide therapy for refractory testicular tumors. Cancer Treat Rev 9A:79–84Google Scholar
  6. 6.
    Brock N (1983) The oxazaphosphorines. Cancer Treat Rev 10A:3–1Google Scholar
  7. 7.
    Brock N, Stekar J, Pohl J, Scheef W (1979) Antidot gegen urotoxische Wirkungen der Oxazaphosphorinderivate Cyclophosphamid, Ifosfamid und Trofosfamid. Naturwissenschaften 66:60–61Google Scholar
  8. 8.
    Brock N, Hilgard P, Pohl J, Ormstad K, Orrenius S (1984) Pharmacokinetics and mechanism of action of detoxifying low-molecular weight thiols. J Cancer Res Clin Oncol 108: 87–97Google Scholar
  9. 9.
    Cavalli F, Klepp O, Renard J, Rohrt M, Alberto P (1981) A phase II story of oral VP-16-213 in non-seminomatous testicular cancer. Eur J Cancer 17:245–249Google Scholar
  10. 10.
    Corringham R, Gilmore M, Prentice HG, Boesen E (1983) High-dose melphalan with autologous bone marrow transplant. Cancer 52:1783–1787Google Scholar
  11. 11.
    Creaven PJ, Allan LM, Cohen MH (1976) Studies on the clinical pharmacology and toxicity of ifosfamide (NSC 109 724). Cancer Treat Rep 60:445–449Google Scholar
  12. 12.
    Einhorn LH (1981) Testicular cancer: a model for a curable neoplasm. The Richard and Hinda Rosenthal Foundation Award Lecture. Cancer Res 41:3275–3280Google Scholar
  13. 13.
    Fitzharris BM, Kaye SB, Saverymotto S, Newlands ES, Barrett A, Peckham MJ, McElwain TJ (1980) VP-16-213 as a single agent in advanced testicular tumors. Eur J Cancer 16: 1193–1197Google Scholar
  14. 14.
    Goldin A (1982) Ifosfamide in experimental tumor systems. Semin Oncol 9 [Suppl]:14–23Google Scholar
  15. 15.
    Hainsworth JD, Williams SD, Einhorn LH, Birch R, Greco FA (1985) Successful treatment of resistant germinal neoplasms with VP-16 and cisplatin: Results of a Southeastern Cancer Study Group Trial. J Clin Oncol 3:666–671Google Scholar
  16. 16.
    Hartenstein R, Jackel R, Clemm C, Staehler E, Lohrs U, Wilmanns W (1982) Value of ifosfamide in combination chemotherapy of advanced non-seminomatous germ cell tumors. Proc 13th Int Cancer Congress 13:625Google Scholar
  17. 17.
    Hilgard P, Burkert H (1984) Sodium 2-mercaptoethanesulfonate (mesna) and ifosfamide nephrotoxicity. Eur J Cancer 20: 1451–1452Google Scholar
  18. 18.
    Hunter HL, Harrison EF (1982) The anticancer spectrum of ifosfamide. Semin Oncol 9 [Suppl]:96–100Google Scholar
  19. 19.
    Lederman GS, Garnich MB, Canellos GP, Richie JP (1983) Chemotherapy of refractory germ cell cancer with etoposide. J Clin Oncol 1:706–709Google Scholar
  20. 20.
    Morgan LR, Donley PJ, Harrison EF, et al. (1982) Protective effect ofN-acetylcysteine on urotoxicity produced by oxazaphosphorine without interference with anti-cancer activity. Eur J Cancer Clin Oncol 18:113–114Google Scholar
  21. 21.
    Mortimer J, Bukowski RM, Montie J, Hewlett JS, Livingston RB: VP-16-213, cisplatinum, and adriamycin salvage therapy of refractory and/or recurrent non-seminomatous germ cell neoplasmsGoogle Scholar
  22. 22.
    Ozols RF, Ihde D, Jacob J, et al. (1984) Randomized trial of PVeBV (high-dose cisplatin, vinblastine, bleomycin, VP-16) versus PVeB in poor prognosis non-seminomatous testicular cancer. (Abstract) Proc Am Soc Clin Oncol 3:155Google Scholar
  23. 23.
    Robinson WA, Hartmann DW, Mangalik A, Morton N, Joshi JH (1981) Autologous nonfrozen bone marrow transplantation after intensive chemotherapy: A pilot study. Acta Haematol 66:145–153Google Scholar
  24. 24.
    Samson MK, Rivkin SE, et al. Jones SE (1984) Dose-response and dose survival advantage for high versus low dose cisplatin combined with vinblastine and bleomycin in disseminated testicular cancer. Cancer 53:1029–1035Google Scholar
  25. 25.
    Schabel FM, Trader MW, Laster WR, Corbett TH, Griswold DP (1979)cis-Dichlorodiammine platinum (II): combination chemotherapy and cross resistance studies with tumors of mice. Cancer Treat Rep 63:1459–1473Google Scholar
  26. 26.
    Scheef W, Klein HO, Brock N, Burkert H, Günther U, Hoefer-Janker H, Mitrenga D, Schnitker D, Voigtmann R (1979) Controlled clinical studies with an antidote against the urotoxicity of oxazaphosphorines: preliminary results. Cancer Treat Rep 63:501–505Google Scholar
  27. 27.
    Scheulen M, Niederle N, Bierbaum W, Higi M, Schilcher R, Seeber S, Schmidt CG (1980) Isophosphamide in refractory metastasized tumors: a clinical phase II study. Current chemotherapy. Proceedings of the 11th International Chemotherapy Congress, Boston, vol II. American Society for Microbiology, Washington, pp 1514–1518Google Scholar
  28. 28.
    Scheulen ME, Niederle N, Höffken K, Schütte J, Seeber S, Schmidt CG (1985) Ifosfamide-mesna alone or in combination with etoposide: salvage therapy for patients with metastasized non-seminomatous testicular cancer. Proc Am Soc Clin Oncol 4:97Google Scholar
  29. 29.
    Schmoll HJ (1982) The role of ifosfamide in testicular cancer. (Abstract) Proc 13th Int Cancer Congress 13:626Google Scholar
  30. 30.
    Trump DL, Hortvet L (1985) Etoposide and very high dose cisplatin salvage therapy for patients with advanced germ cell neoplasms. Cancer Treat Rep 69:259–261Google Scholar
  31. 31.
    Vogelzang NJ, Kennedy BJ (1981) Salvage chemotherapy for refractory germ cell tumors. (Abstract) Proc Am Assoc Cancer Res 22:471Google Scholar
  32. 32.
    Vugrin D, Whitmore WF, Sogani PC, Bains M, Herr HW, Golbey RB (1981) Combined chemotherapy and surgery in treatment of advanced germ cell tumors. Cancer 47:2228–31Google Scholar
  33. 33.
    Wheeler BM, Loehrer PJ, Williams SD, Einhorn LH (1986) Ifosfamide in refractory male germ cell tumors. J Clin Oncol 4:28Google Scholar
  34. 34.
    Williams SD, Einhorn LH (1982) Etoposide salvage therapy for refractory germ cell tumors: an update. Cancer Treat Rev 9A:67–71Google Scholar
  35. 35.
    Williams SD, Turner S, Loehrer PJ, Einhorn LH (1983) Testicular cancer: Results of re-induction therapy. Proc Am Soc Clin Oncol 2:137Google Scholar
  36. 36.
    Wolff SN, Johnson DH, Hainsworth JD, Greco FA (1984) High-dose VP-16-213 monotherapy for refractory germinal malignancies: a phase II study. J Clin Oncol 2:271–274Google Scholar

Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • Lawrence H. Einhorn
    • 1
  1. 1.Department of Medicine Indiana University HospitalIndianapolisUSA

Personalised recommendations