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.

  • Correspondence
  • Published:

Intermediate-dose melphalan with stem-cell support in platinum-refractory ovarian cancer

Bone Marrow Transplantation volume 33, pages 1261–1262 (2004)Cite this article

Ovarian cancer is the fourth leading cause of cancer-related death in women. There is no proven curative therapy for patients with ovarian cancer relapsing after platinum-containing regimens.1,2 High-dose chemotherapy with autotransplantation does not seem strikingly superior to standard therapy for resistant/relapsed disease and is often associated with significant toxicity.3,4 However, the Norton–Simon model of tumor-growth kinetics predicts that multiple, rapidly cycled treatments yield better results compared with a single treatment.5 Based on this hypothesis and the existence of an in vivo dose effect of alkylating agents in ovarian cancer,6 we started a pilot study to evaluate the tolerability of double intermediate-dose melphalan supported by autologous stem cells in patients with refractory ovarian cancer and poor performance status. The interval between the two courses of melphalan was at least 45–60 days to avoid excessive toxicity in these heavily pre-treated patients.

In total, 10 patients with advanced ovarian cancer (FIGO stages III/IV) were enrolled from April 2000 to February 2003. All patients were pretreated: five had received two chemotherapy lines and five had undergone three lines. All patients had received platinum- and taxol-containing regimens, and six patients had also received topotecan alone or in combination. The median time between platinum administration and disease progression was 3 months (range 1–5 months). At the time of the experimental therapy, median age was 52 (range 33–68) and the median time from diagnosis was 24 months (range 9–51). Nine patients had progressive disease (PD), and one was in partial remission (PR) after the last treatment. Seven patients had poor performance status (ECOG⩾2). Other patient characteristics are shown in Table 1. In all but one patient, cyclophosphamide 4.5 g/m2 plus G-CSF (5 μg/kg/day, s.c.) was used to mobilize stem cells. One patient, failing mobilization with this, was mobilized with G-CSF alone (10 μg/kg/day, s.c.). Mobilization chemotherapy was tolerated well and the median number of CD34+ cells per kg collected was 5.1 × 106 (range 2.9–7.4). Patients received two cycles of intravenous melphalan at a dose of 100 mg/m2, each followed 24 h later by stem cells.

Table 1 Patient characteristics and therapeutic outcome
Full size table

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

References

  1. Brun JL, Feyler A, Chene G et al. Long-term results and prognostic factors in patients with epithelial ovarian cancer. Gynecol Oncol 2000; 78: 21–27.

    Article  CAS  PubMed  Google Scholar 

  2. Yancik R . Ovarian cancer: age contrasts in incidence, histology, disease, stage at diagnosis, and mortality. Cancer 1993; 71: 517–523.

    Article  CAS  PubMed  Google Scholar 

  3. Legros M, Dauplat J, Fleury J et al. High-dose chemotherapy with haematopoietic 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 

  4. Stiff PJ, Bayer R, Kerger C . 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 

  5. Norton L, Day R . Potential innovations in scheduling of cancer chemotherapy. In: DeVita Jr VT, Hellman S, Rosenberg SA (eds.). Important Advances in Oncology. Lippincott: Philadelphia, PA, 1991; pp 57–72.

    Google Scholar 

  6. 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 

  7. Schilder RJ, Gallo JM, Millenson MM et al. Phase I of multiple cycles of high-dose carboplatin, paclitaxel, and topotecan with peripheral blood stem cell support as front-line therapy. J Clin Oncol 2001; 19: 1183–1194.

    Article  CAS  PubMed  Google Scholar 

  8. Donato ML, Gershenson DM, Wharton JT et al. High-dose topotecan, melphalan, and cyclophosphamide (TMC) with stem cell support: a new regimen for the treatment of advanced ovarian cancer. Gynecol Oncol 2001; 82: 420–426.

    Article  CAS  PubMed  Google Scholar 

  9. Holmberg LA, Demirer T, Rowley S et al. High-dose busulfan, melphalan, and thiotepa followed by autologous peripheral blood stem cell (PBSC) rescue in patients with advanced stage III/IV ovarian cancer. Bone Marrow Transplant 1998; 22: 651–659.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  11. Stiff PJ, Veum-Stone J, Lazarus HM et al. High-dose chemotherapy and autologous stem-cell transplantation for ovarian cancer: an autologous blood and marrow transplant registry report. Ann Intern Med 2000; 133: 504–515.

    Article  CAS  PubMed  Google Scholar 

  12. Bookman MA, Malmstrom H, Bolis G et al. Topotecan for the treatment of advanced epithelial ovarian cancer: an open-label phase II study in patients treated after prior chemotherapy that contained cisplatin or carboplatin and paclitaxel. J Clin Oncol 1998; 16: 3345–3352.

    Article  CAS  PubMed  Google Scholar 

  13. Aravantinos G, Bufaloukos D, Fountzillas G et al. Phase II study of docetaxel-vinorelbine in platinum-resistant, paclitaxel-pretreated ovarian cancer. Ann Oncol 2003; 14: 1094–1099.

    Article  CAS  PubMed  Google Scholar 

  14. D'Agostino G, Amant F, Berteloot P et al. Phase II study of gemcitabine in recurrent platinum- and paclitaxel-resistant ovarian cancer. Gynecol Oncol 2003; 88: 266–269.

    Article  CAS  PubMed  Google Scholar 

  15. Boduka DC, Levenback C, Wolf JK et al. Phase II of irinotecan in patients with metastatic epithelial ovarian cancer or peritoneal cancer. J Clin Oncol 2003; 2: 291–297.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Oncology and Hematology, Istituto Clinico Humanitas, Rozzano, Milan, Italy

    M Magagnoli, G Masci, L Castagna, L Rimassa, S Bramanti & A Santoro

Authors
  1. M Magagnoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G Masci
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L Castagna
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L Rimassa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S Bramanti
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A Santoro
    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

Magagnoli, M., Masci, G., Castagna, L. et al. Intermediate-dose melphalan with stem-cell support in platinum-refractory ovarian cancer. Bone Marrow Transplant 33, 1261–1262 (2004). https://doi.org/10.1038/sj.bmt.1704527

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704527

Search

Advanced search

Quick links