Skip to main content

Advertisement

Log in

The efficacy of amrubicin on central nervous system metastases originating from small-cell lung cancer: a case series of eight patients

  • SHORT REPORT
  • Published:
Investigational New Drugs Aims and scope Submit manuscript

Summary

Background Central nervous system (CNS) metastases caused by small-cell lung cancer (SCLC) are incurable and therefore fatal. Although such metastases are usually treated with chemotherapy or radiotherapy, their sensitivity to these treatment measures is unclear. Amrubicin appears to be a promising agent for relapsed SCLC, but its effectiveness in CNS metastases originating from SCLC is unknown. Methods Between April 2002 and December 2009, 110 SCLC patients with CNS metastasis were treated at Shizuoka Cancer Center. Of these, we retrospectively reviewed 8 consecutive cases with CNS metastases originating from relapsed SCLC that were treated with amrubicin as a second-line therapy. Results We recorded three sensitive relapses and five refractory cases. Amrubicin yielded a CNS response rate of 50 % (2 partial responses and 2 complete response; 95 % CI, 21.5–78.5 %) and the disease control rate for CNS lesions was 87.5 % (95 % CI, 52.9–97.8 %). All of the sensitive relapse patients achieved a partial response. The median time to progression for CNS metastases was 150.5 days (95 % CI, 9–171 days), and the median survival time from the start of amrubicin administration was 230.5 days (95 % CI, 89–619 days). We also report a dramatic improvement in one patient’s radiological result of intramedullary spinal cord metastasis and alleviation of her symptoms following amrubicin monotherapy including this case series. Conclusions The results of this study suggest that amrubicin is active in patients with CNS metastases originating from SCLC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

CNS:

Central nervous system

SCLC:

Small-cell lung cancer

CNS-TTP:

Time to progression of CNS metastases

ISCM:

Intramedullary spinal cord metastasis

CT:

Computed tomography

MRI:

Magnetic resonance imaging

References

  1. Patchell RA (1991) Brain metastases. Neurol Clin 9:817–824

    CAS  PubMed  Google Scholar 

  2. Hirsch FR, Paulson OB, Hansen HH, Larsen SO (1983) Intracranial metastases in small cell carcinoma of the lung. Prognostic aspects. Cancer 51:529–533

    Article  CAS  PubMed  Google Scholar 

  3. Grossi F, Scolaro T, Tixi L, Loprevite M, Ardizzoni A (2001) The role of systemic chemotherapy in the treatment of brain metastases from small-cell lung cancer. Crit Rev Oncol Hematol 37:61–67

    Article  CAS  PubMed  Google Scholar 

  4. Onoda S, Masuda N, Seto T, Eguchi K, Takiguchi Y et al (2006) Phase II trial of amrubicin for treatment of refractory or relapsed small-cell lung cancer: Thoracic Oncology Research Group Study 0301. J Clin Oncol 24:5448–5453

    Article  CAS  PubMed  Google Scholar 

  5. Inoue A, Sugawara S, Yamazaki K, Maemondo M, Suzuki T et al (2008) Randomized phase II trial comparing amrubicin with topotecan in patients with previously treated small-cell lung cancer: North Japan Lung Cancer Study Group Trial 0402. J Clin Oncol 26:5401–5406

    Article  CAS  PubMed  Google Scholar 

  6. Murakami H, Yamamoto N, Shibata T, Takeda K, Ichinose Y et al (2014) A single-arm confirmatory study of amrubicin therapy in patients with refractory small-cell lung cancer: Japan Clinical Oncology Group Study (JCOG0901). Lung Cancer 84(1):67–72

    Article  PubMed  Google Scholar 

  7. O’Brien ME, Ciuleanu TE, Tsekov H, Shparyk Y, Cucevia B et al (2006) Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol 24:5441–5447

    Article  PubMed  Google Scholar 

  8. Ettinger DS, Jotte R, Lorigan P, Gupta V, Garbo L et al (2010) Phase II study of amrubicin as second-line therapy in patients with platinum-refractory small-cell lung cancer. J Clin Oncol 28:2598–2603

    Article  PubMed  Google Scholar 

  9. Jotte R, Conkling P, Reynolds C, Galsky MD, Klein L et al (2010) Randomized phase II trial of single-agent amrubicin or topotecan as second-line treatment in patients with small-cell lung cancer sensitive to first-line platinum-based chemotherapy. J Clin Oncol 29(3):287–293

    Article  PubMed  Google Scholar 

  10. von Pawel J, Jotte R, Spigel DR, O’Brien ME, Socinski MA et al (2014) Randomized phase III trial of amrubicin versus topotecan as second-line treatment for patients with small-cell lung cancer. J Clin Oncol 32(35):4012–4019

    Article  Google Scholar 

  11. Borgelt B, Gelber R, Kramer S, Brady LW, Chang CH et al (1980) The palliation of brain metastases: final results of the first two studies by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 6:1–9

    Article  CAS  PubMed  Google Scholar 

  12. Lagerwaard FJ, Levendag PC, Nowak PJ, Eijkenboom WM, Hanssens PE et al (1999) Identification of prognostic factors in patients with brain metastases: a review of 1292 patients. Int J Radiat Oncol Biol Phys 43:795–803

    Article  CAS  PubMed  Google Scholar 

  13. Saito EY, Viani GA, Ferrigno R, Nakamura RA, Novaes PE et al (2006) Whole brain radiation therapy in management of brain metastasis: results and prognostic factors. Radiat Oncol 1:20

    Article  PubMed Central  PubMed  Google Scholar 

  14. Castrucci WA, Knisely JP (2008) An update on the treatment of CNS metastases in small cell lung cancer. Cancer J 14:138–146

    Article  PubMed  Google Scholar 

  15. Sung C, Blaney SM, Cole DE, Balis FM, Dedrick RL (1994) A pharmacokinetic model of topotecan clearance from plasma and cerebrospinal fluid. Cancer Res 54:5118–5122

    CAS  PubMed  Google Scholar 

  16. Baker SD, Heideman RL, Crom WR, Kuttesch JF, Gajjar A et al (1996) Cerebrospinal fluid pharmacokinetics and penetration of continuous infusion topotecan in children with central nervous system tumors. Cancer Chemother Pharmacol 37:195–202

    Article  CAS  PubMed  Google Scholar 

  17. Ardizzoni A, Hansen H, Dombernowsky P, Gamucci T, Kaplan S et al (1997) Topotecan, a new active drug in the second-line treatment of small-cell lung cancer: a phase II study in patients with refractory and sensitive disease. The European Organization for Research and Treatment of Cancer Early Clinical Studies Group and New Drug Development Office, and the Lung Cancer Cooperative Group. J Clin Oncol 15:2090–2096

    CAS  PubMed  Google Scholar 

  18. Korfel A, Oehm C, von Pawel J, Keppler U, Deppermann M et al (2002) Response to topotecan of symptomatic brain metastases of small-cell lung cancer also after whole-brain irradiation. a multicentre phase II study. Eur J Cancer 38:1724–1729

    Article  CAS  PubMed  Google Scholar 

  19. Mut M, Schiff D, Shaffrey ME (2005) Metastasis to nervous system: spinal epidural and intramedullary metastases. J Neurooncol 75:43–56

    Article  PubMed  Google Scholar 

  20. Wagner M, Besse B, Balleyguier C, Soria JC (2008) Leptomeningeal and medullary response to second-line erlotinib in lung adenocarcinoma. J Thorac Oncol 3:677–679

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Sources of support: This work was supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labor, and Welfare of Japan. We appreciate Ms. Yuka Matsui for her technical assistance of manuscript submission.

Competing interest

The authors declare that they have no competing interests.

Author’s contributions

SM and KK conceived of the study and contributed to writing and editing the report. RK, HA, AO, TS, AT and YN participated in data acquisition and interpretation. HK, TT and ME advised on clinical matters and the interpretation of the data and contributed to the writing of the report and helped to draft the manuscript. HM and TN helped to perform the statistical analysis. NY provided overall project management. All authors read and approved the final manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kyoichi Kaira.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Miura, S., Kaira, K., Kaira, R. et al. The efficacy of amrubicin on central nervous system metastases originating from small-cell lung cancer: a case series of eight patients. Invest New Drugs 33, 755–760 (2015). https://doi.org/10.1007/s10637-015-0233-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10637-015-0233-7

Keywords

Navigation