Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Ovarian Cancer

Phase II trial of high-dose intravenous doxorubicin, etoposide, and cyclophosphamide with autologous stem cell support in patients with residual or responding recurrent ovarian cancer

Bone Marrow Transplantation volume 28, pages 859–863 (2001)Cite this article

Abstract

This study was performed in order to evaluate the toxicities, progression-free and overall survival of patients with responsive residual or recurrent ovarian cancer treated with high-dose chemotherapy. Twenty-seven patients were treated. Doxorubicin, 165 mg/m2 over 96 h (days −12 to −8), etoposide 700 mg/m2 every day ×3 (days −6 to −4), and cyclophosphamide 4.2 g/m2 on d −3 was followed by stem cells and granulocyte colony-stimulating factor. The median days of granulocyte count <500/μl was 14 (range 10–42) and platelets <20 000/μl was 13 (range 2–80). Median numbers of red cell and platelet transfusions were 15 (5–16) and 14 (4–103). Toxicity included mucositis requiring narcotic analgesia in all patients. Asymptomatic decreases in ejection fraction to values <50% were observed in four patients. No clinical congestive heart failure was observed. One death due to sepsis was observed. Median progression-free survival is 7.5 months (1.0–56 months); five patients remain alive, two of whom remain progression-free at 19.5 and 24.5 months post transplant. Median overall survival is 14.0 months (1–68 months). We conclude that high-dose anthracyclines may be safely administered to ovarian cancer patients. The short overall and progression-free survivals observed in our population suggest that this combination is not optimal. Bone Marrow Transplantation (2001) 28, 859–863.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Alberts DS, Green S, Hannigan EV et al. Improved therapeutic index of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide: final report by the Southwest Oncology Group of a phase III randomized trial in stages III and IV ovarian cancer J Clin Oncol 1992 10: 706–717

    Article  CAS  PubMed  Google Scholar 

  2. Howell SB, Zimm S, Markman M et al. Long-term survival of advanced refractory ovarian carcinoma patients with small-volume disease treated with intraperitoneal chemotherapy J Clin Oncol 1987 5: 1607–1612

    Article  CAS  PubMed  Google Scholar 

  3. Swenerton K, Jeffrey J, Stuart G et al. Cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide in advanced ovarian cancer: a randomized phase III study of the national cancer institute of Canada clinical trials group J Clin Oncol 1992 10: 718–726

    Article  CAS  PubMed  Google Scholar 

  4. Hryniuk W . The importance of dose intensity in the outcome of chemotherapy. In: Hellman, S, DeVita V, Rosenberg S (eds) Important Advances in Oncology Lippincott: Philadelphia 1988 pp 121–141

    Google Scholar 

  5. Tepler I, Cannistra SA, Frei E et al. Use of peripheral-blood progenitor cells abrogates the myelotoxicity of repetitive outpatient high-dose carboplatin and cyclophosphamide chemotherapy J Clin Oncol 1993 11: 1583–1591

    Article  CAS  PubMed  Google Scholar 

  6. Mulder POM, Willemse PHG, Aalders JG et al. High-dose chemotherapy with autologous bone marrow transplantation in patients with refractory ovarian cancer Eur J Cancer Clin Oncol 1989 25: 645–649

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  8. Dottino PR, Goodman H, Kredentser D et al. Clinical trial of etoposide and cisplatin as salvage therapy in advanced ovarian carcinoma Gynecol Oncol 1987 27: 350–356

    Article  CAS  PubMed  Google Scholar 

  9. Jacobs AJ, Sommers GM, Homan SM et al. Therapy of ovarian carcinoma: the relationship of dose level and treatment intensity to survival Gynecol Oncol 1988 31: 233–245

    Article  CAS  PubMed  Google Scholar 

  10. Somlo G, Doroshow JH, Forman S et al. High-dose doxorubicin, etoposide, and cyclophosphamide with stem cell reinfusion in patients with metastatic or high-risk primary breast cancer Cancer 1994 73: 1678–1685

    Article  CAS  PubMed  Google Scholar 

  11. Kaplan EL, Meier P . Nonparametric estimation from incomplete observations J Am Stat Assoc 1958 53: 457–481

    Article  Google Scholar 

  12. Cannistra SA . Cancer of the ovary New Engl J Med 1993 329: 1550–1559

    Article  CAS  PubMed  Google Scholar 

  13. Ozols RF, Vermorken JB . Chemotherapy of advanced ovarian cancer: current status and future directions Semin Oncol 1997 24: S2–1–S2–9

    Google Scholar 

  14. Morgan Jr RJ, Copeland L, Gershenson D et al. NCCN ovarian cancer practice guidelines. The National Comprehensive Cancer Network Oncology (Huntingt) 1996 10: 293–310

    Google Scholar 

  15. Neijt JP, ten Bokkel Huinink WW, van der Burg ME et al. Randomized trial comparing two combination chemotherapy regimens (CHAP-5 v CP) in advanced ovarian carcinoma J Clin Oncol 1987 5: 1157–1168

    Article  CAS  PubMed  Google Scholar 

  16. Omura GA, Bundy BN, Berek JS et al. Randomized trial of cyclophosphamide plus cisplatin with or without doxorubicin in ovarian carcinoma: a Gynecologic Oncology Group Study J Clin Oncol 1989 7: 457–465

    Article  CAS  PubMed  Google Scholar 

  17. Luck HJ, Meier W, Moebus V et al. Cisplatin/paclitaxel vs carboplatin/paclitaxel in ovarian cancer: update of an Arbeitsgemeinschaft Gynaekologische Onkologie Study Group trial Proc Am Soc Clin Oncol 1999 18: 356 (Abstr. 1374)

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  19. Ozols RF, Bundy BN, Fowler J et al. Randomized phase III study of cisplatin/paclitaxel versus carboplatin/paclitaxel in optimal stage III epithelial ovarian cancer: a Gynecologic Oncology Group trial Proc Am Soc Clin Oncol 1999 18: 356 (Abstr. 1373)

    Google Scholar 

  20. A'Hern RP, Gore ME . Impact of doxorubicin on survival in advanced ovarian cancer J Clin Oncol 1995 13: 726–732

    Article  CAS  PubMed  Google Scholar 

  21. Alberts DS, Liu PY, Hannigan EV et al. Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer New Engl J Med 1996 335: 1950–1955

    Article  CAS  PubMed  Google Scholar 

  22. Thigpen T, Vance R, Khansur T, Malamud F . The role of chemotherapy in the management of coelomic epithelial carcinoma of the ovary Cancer Invest 1997 15: 277–287

    Article  CAS  PubMed  Google Scholar 

  23. Knopf K, Brown M, Kohn EC . Lack of improvement in survival in patients with relapsed or refractory epithelial ovarian cancer, 1980–1997 Proc Am Soc Clin Oncol 1998 17: 359

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  25. Stiff PJ, Bayer R, Kerger C et al. High-dose chemotherapy with autologous transplantation for persistent/relapsed ovarian cancer: a multivariate analysis of survival for 100 consecutively treated patients J Clin Oncol 1997 15: 1309–1317

    Article  CAS  PubMed  Google Scholar 

  26. 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  PubMed  Google Scholar 

  27. Shinozuka T, Miyamoto T, Muramatsu T et al. High dose chemotherapy with autologous stem cell support in the treatment of patients with ovarian carcinoma Cancer 1999 85: 1555–1564

    Article  CAS  PubMed  Google Scholar 

  28. Cure H, Battista C, Guastalla J et al. Phase III randomized trial of high dose chemotherapy (HDC) and peripheral blood stem cell (PBSC) support as consolidation in patients (pts) with responsive low-burden advanced ovarian cancer (AOC): preliminary results of a GINECO/FNCLCC/SFGM-TC study Proc Am Soc Clin Oncol 2001 20: 204a

    Google Scholar 

Download references

Acknowledgements

This work was supported in part by NCI Cancer, Center Support Grant CA 33572 and by CA 63265.

Author information

Authors and Affiliations

  1. Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA

    RJ Morgan, JH Doroshow, L Leong, S Shibata, S Forman, V Hamasaki, K Margolin, G Somlo, M McNamara, J Raschko, W Chow & Y Yen

  2. Department of Gynecologic Oncology, City of Hope National Medical Center, Duarte, CA, USA

    S Vasilev & K McGonigle

  3. Department of Biostatistics, City of Hope National Medical Center, Duarte, CA, USA

    J Longmate

  4. City of Hope/Samaritan Bone Marrow Transplant Program, Phoenix, AZ, USA

    J Schriber & J Alvarnas

Authors
  1. RJ Morgan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. JH Doroshow
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L Leong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J Schriber
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S Shibata
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S Forman
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. V Hamasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. K Margolin
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. G Somlo
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. J Alvarnas
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. M McNamara
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. J Longmate
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. J Raschko
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. W Chow
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. S Vasilev
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. K McGonigle
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Y Yen
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Morgan, R., Doroshow, J., Leong, L. et al. Phase II trial of high-dose intravenous doxorubicin, etoposide, and cyclophosphamide with autologous stem cell support in patients with residual or responding recurrent ovarian cancer. Bone Marrow Transplant 28, 859–863 (2001). https://doi.org/10.1038/sj.bmt.1703243

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1703243

Keywords

This article is cited by

Search

Advanced search

Quick links