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Solid Tumours

High-dose melphalan-based chemotherapy and autologous stem cell transplantation after second look laparotomy in patients with chemosensitive advanced ovarian carcinoma: long-term results

Abstract

The importance of dose intensity has been suggested in ovarian carcinoma. We retrospectively evaluated the long-term results of melphalan-based high-dose chemotherapy (HDC) with hematopoietic rescue in a unicentric series of 33 patients with advanced ovarian cancer sensitive to first-line chemotherapy. Before HDC, treatment with debulking surgery and platinum-based chemotherapy was followed by second-look operation (SLO). HDC consisted of melphalan (n = 8), melphalan and cyclophosphamide (n = 9), or melphalan, etoposide and carboplatinum (n = 16). Toxicity was mainly hematological. One death occurred from infection during aplasia. With a median follow-up of 60 months after intensification, the 5-year progression-free survival (PFS) rate was 29% and the 5-year overall survival (OS) rate was 45%. Survival differed significantly according to tumor status at SLO. Women with microscopic or macroscopic disease at SLO, ie with a pathological partial response to first-line therapy (PPR), had survivals of 7% at 5 years, similar to other salvage therapies. Better results were obtained in the 20 women with a complete pathological response (PCR) at SLO with 43% 5-year PFS (median, 51 months) and 75% 5-year OS (median not reached). In conclusion, melphalan-based HDC with hematopoietic rescue had an acceptable toxicity in patients with chemosensitive advanced ovarian cancer. In situations of salvage therapy for patients in PPR, this treatment was not effective in long-term analysis. On the contrary, long-term results were favorable in patients with PCR, suggesting further prospective randomized studies comparing HDC and other consolidation treatments should be undertaken in this particular situation. Bone Marrow Transplantation (2000) 26, 61–67.

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References

  1. Cannistra S . A. Cancer of the ovary New Engl J Med 1993 329: 1550–1559

    Article  CAS  Google Scholar 

  2. McGuire WP, Hoskins WJ, Brady MF et al. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage 3 and 4 ovarian cancer New Engl J Med 1996 334: 1–6

    Article  CAS  Google Scholar 

  3. Frei E III, Canellos GP . Dose: a critical factor in cancer chemotherapy Am J Med 1980 69: 585–594

    Article  Google Scholar 

  4. Maraninchi D, Abecassis M, Gastaut JA et al. High-dose melphalan with autologous bone marrow rescue for the treatment of advanced adult solid tumors Cancer Treat Rep 1984 68: 471–474

    CAS  PubMed  Google Scholar 

  5. Frei E, Antman B, Teicher B et al. Bone marrow autotransplantation for solid tumors. Prospects J Clin Oncol 1989 7: 515–526

    Article  Google Scholar 

  6. Levin L, Hryniuk W . Dose intensity analysis of chemotherapy regimens in ovarian carcinoma J Clin Oncol 1987 5: 756–767

    Article  CAS  Google Scholar 

  7. Ellis ED, Williams SF, Moormeier JA . A phase I–II study of high-dose cyclophosphamide, thiotepa and escalating doses of mitoxantrone with autologous stem cell rescue in patients with refractory malignancies Bone Marrow Transplant 1990 6: 439–442

    CAS  PubMed  Google Scholar 

  8. Viens P, Maraninchi D, Legros M et al. High-dose melphalan and autologous marrow rescue in advanced epithelial ovarian carcinoma: a retrospective analysis of 35 patients treated in France Bone Marrow Transplant 1990 5: 227–233

    CAS  PubMed  Google Scholar 

  9. Thomas ED, Storb R . Technique of human marrow grafting Blood 1970 36: 507–515

    CAS  Google Scholar 

  10. Rubin SC . Second look laparotomy in ovarian cancer. In: Markman M, Hoskins WJ (eds) Cancer of the Ovary Raven Press: New York 1993 175–185

    Google Scholar 

  11. Antman KH, Rowlings PA, Vaughan WP et al. High-dose chemotherapy with autologous hematopoietic stem-cell support for breast cancer in North America J Clin Oncol 1997 15: 1870–1879

    Article  CAS  Google Scholar 

  12. Piver MS . Ovarian carcinoma. A decade of progress Cancer 1984 54: (Suppl. 11) 2706–2715

    Article  CAS  Google Scholar 

  13. Von Hoff DD, Clark GM, Weiss GR et al. Use of in vitro dose response effects to select antineoplastics for high-dose or regional administration regimens J Clin Oncol 1986 4: 1827–1834

    Article  CAS  Google Scholar 

  14. Frei E III, Teicher BA, Holden SA et al. Effect of alkylating agent dose: preclinical studies and possible clinical correlation Cancer Res 1988 48: 6417–6423

    PubMed  Google Scholar 

  15. Lazarus HM, Herzig RH, Graham-Pole J et al. Intensive melphalan chemotherapy and cryopreserved autologous bone marrow transplantation for the treatment of refractory cancer J Clin Oncol 1983 1: 359–367

    Article  CAS  Google Scholar 

  16. Legros M, Dauplat J, Fleury J et al. High-dose chemotherapy with hematopoietic rescue in patients with stage III to IV ovarian cancer: long-term results J Clin Oncol 1997 15: 1302–1308

    Article  CAS  Google Scholar 

  17. Schabel FM Jr, Trader MW, Laster WR Jr et al. Patterns of resistance and therapeutic synergism among alkylating agents Antibiot Chemother 1978 23: 200–215

    Article  Google Scholar 

  18. Lidor YJ, Shpall EJ, Peters WP . Synergistic cytotoxicity of different alkylating agents for epithelial ovarian cancer Int J Cancer 1991 49: 704–710

    Article  CAS  Google Scholar 

  19. Le Corroller AG, Faucher C, Auperin A et al. Autologous peripheral blood progenitor-cell transplantation versus autologous bone marrow transplantation for adults and children with non-leukaemic malignant disease. A randomised economic study Pharmacoeconomics 1997 11: 454–463

    Article  CAS  Google Scholar 

  20. Mascret B, Maraninchi D, Gastaut JA et al. Risk factors for streptococcal septicaemia after marrow transplantation Lancet 1984 1: 1185–1186

    Article  CAS  Google Scholar 

  21. Weaver CH, Schwartzberg LS, Hainsworth J et al. Treatment-related mortality in 1000 consecutive patients receiving high-dose chemotherapy and peripheral blood progenitor cell transplantation in community cancer centers Bone Marrow Transplant 1997 19: 671–678

    Article  CAS  Google Scholar 

  22. Creasman WT . Second-look laparotomy in ovarian cancer Gynecol Oncol 1994 55: S122–S127

    Article  CAS  Google Scholar 

  23. Lawton F, Luesley D, Blackledge G et al. A randomized trial comparing whole abdominal radiotherapy with chemotherapy following cisplatinum cytoreduction in epithelial ovarian cancer. West Midlands Ovarian Cancer Group Trial II Clin Oncol (R Coll Radiol) 1990 2: 4–9

    Article  CAS  Google Scholar 

  24. Pujade-Lauraine E, Guastalla JP et al. Intraperitoneal recombinant interferon gamma in ovarian cancer patients with residual disease at second-look laparotomy J Clin Oncol 1996 14: 343–350

    Article  CAS  Google Scholar 

  25. Bruzzone M, Rubagotti A, Gadducci A et al. Intraperitoneal carboplatin with or without interferon-alpha in advanced ovarian cancer patients with minimal residual disease at second look: a prospective randomized trial of 111 patients. GONO Gruppo Oncologic Nord Ovest Gynecol Oncol 1997 65: 499–505

    Article  CAS  Google Scholar 

  26. Goldhirsch A, Greiner R, Dreher E et al. Treatment of advanced ovarian cancer with surgery, chemotherapy, and consolidation of response by whole-abdominal radiotherapy Cancer 1988 62: 40–47

    Article  CAS  Google Scholar 

  27. Schray MF, Martinez A, Howes AE et al. Advanced epithelial ovarian cancer: salvage whole abdominal irradiation for patients with recurrent or persistent disease after combination chemotherapy J Clin Oncol 1988 6: 1433–1439

    Article  CAS  Google Scholar 

  28. Shpall EJ, Cagnoni PJ, Bearman SI et al. High dose chemotherapy with autologous hematopoietic cell support (AHCS) for the treatment of epithelial ovarian cancer. 31st Annual Meeting of the American Society of Clinical Oncology, Los Angeles, CA, USA, 20–23 May 1995 360–364

  29. Lotz JP, Bouleuc C, Andre T et al. Tandem high-dose chemotherapy with ifosfamide, carboplatin, and teniposide with autologous bone marrow transplantation for the treatment of poor prognosis common epithelial ovarian carcinoma Cancer 1996 77: 2550–2559

    Article  CAS  Google Scholar 

  30. Gadducci A, Sartori E, Maggino T et al. Analysis of failures after negative second-look in patients with advanced ovarian cancer: an Italian multicenter study Gynecol Oncol 1998 68: 150–155

    Article  CAS  Google Scholar 

  31. Bolis G, Villa A, Guarnerio P et al. Survival of women with advanced ovarian cancer and complete pathologic response at second-look laparotomy Cancer 1996 77: 128–131

    Article  CAS  Google Scholar 

  32. Sorbe B, Trope C, Nordal R et al. Chemotherapy versus radiotherapy as consolidation treatment of ovarian carcinoma stage III at surgical complete remission from induction chemotherapy Proc Am Soc Clin Oncol 1996 15: 287

    Google Scholar 

  33. Condra KS, Mendenhall WM, Morgan LS, Marcus RB Jr . Consolidative 32P after second-look laparotomy for ovarian carcinoma Radiat Oncol Invest 1998 6: 97–102

    Article  CAS  Google Scholar 

  34. Franchin G, Tumolo S, Scarabelli C et al. Whole abdomen radiation therapy after a short chemotherapy course and second-look laparotomy in advanced ovarian cancer Gynecol Oncol 1991 41: 206–211

    Article  CAS  Google Scholar 

  35. Fennelly DW, Aghajanian C, Shapiro F et al. Dose escalation of paclitaxel with high-dose carboplatin using peripheral blood progenitor cell support in patients with advanced ovarian cancer Semin Oncol 1997 24: (Suppl. 2) S26–S30

    CAS  Google Scholar 

  36. Benedetti-Panici P, Greggi S, Scambia G et al. High-dose chemotherapy with autologous peripheral stem cell support in advanced ovarian cancer Ann Med 1995 27: 133–138

    Article  CAS  Google Scholar 

  37. Crown J, Wassherheit C, Hakes T et al. Rapid delivery of multiple high-dose chemotherapy courses with granulocyte colony-stimulating factor and peripheral blood-derived hematopoietic progenitor cells J Natl Cancer Inst 1992 84: 1935–1936

    Article  CAS  Google Scholar 

  38. Viens P, Gravis G, Genre D et al. High-dose sequential chemotherapy with stem cell support for non-metastatic breast cancer Bone Marrow Transplant 1997 20: 199–203

    Article  CAS  Google Scholar 

Download references

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This work was supported by grants from the Ligue Nationale Contre le Cancer.

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Bertucci, F., Viens, P., Delpero, J. et al. High-dose melphalan-based chemotherapy and autologous stem cell transplantation after second look laparotomy in patients with chemosensitive advanced ovarian carcinoma: long-term results. Bone Marrow Transplant 26, 61–67 (2000). https://doi.org/10.1038/sj.bmt.1702468

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