Cancer Res Treat.  2016 Apr;48(2):843-847. 10.4143/crt.2014.234.

Intrathecal Trastuzumab Treatment in Patients with Breast Cancer and Leptomeningeal Carcinomatosis

• Park WY
• Kim HJ
• Kim K
• Bae SB
• Lee N
• Lee KT
• Won JH
• Park HS
• Lee SC

• KMID: 2454364
• DOI: http://doi.org/10.4143/crt.2014.234

Abstract

Leptomeningeal carcinomatosis is a fatal manifestation of metastatic breast cancer. Investigation of intrathecal (IT) trastuzumab for leptomeningeal carcinomatosis is currently underway; however, there has been no consensus. We report on two cases of human epidermal growth factor receptor 2 positive (HER2+) breast cancer following IT trastuzumab for leptomeningeal carcinomatosis. The first patient was treated with weekly IT 15 mg methotrexate plus IT 50 mg trastuzumab for 7 months, followed by IT trastuzumab (50 mg > 25 mg) for 18 months. The other patient received IT trastuzumab with systemic chemotherapy (trastuzumab and/or paclitaxel) for 13 months. Good control of leptomeningeal disease was achieved with IT trastuzumab in both patients, with survival durations of 20 and 29 months, respectively. We suggest that IT trastuzumab is a promising treatment for patients with HER2+ breast cancer and leptomeningeal carcinomatosis.

Keyword

Leptomeningeal carcinomatosis; Trastuzumab; Intrathecal injection

MeSH Terms

Breast Neoplasms*
Breast*
Consensus
Drug Therapy
Humans
Injections, Spinal
Meningeal Carcinomatosis*
Methotrexate
Receptor, Epidermal Growth Factor
Trastuzumab*
Methotrexate
Receptor, Epidermal Growth Factor
Trastuzumab

Figure

• 

  Fig. 1. Case 1 contrast-enhanced T1-weighted brain magnetic resonance image (MRI). (A) Multifocal enhanced nodules were detected in both frontal, the right parietal, and both cerebellar hemispheres at the beginning of intrathecal (IT) trastuzumab in April 2012. (B) A remarkable improvement in the leptomeningeal nodules was detected after 5 months of IT trastuzumab therapy in September 2012. (C) No evidence of newly developed enhancing nodules was detected in January 2013 after more than 9 months of IT trastuzumab therapy. Brain MRI shows complete remission of the brain mass (by Response Evaluation Criteria in Solid Tumors).

• 

  Fig. 2. Case 2 contrast-enhanced T1-weighted brain magnetic resonance image (MRI). (A) Contrast-enhanced MRI of the brain showed new multifocal leptomeningeal seeding in both Sylvian fissures, the prepontine cistern, the perimesencephalon, and the left cerebellopontine angle at the beginning of intrathecal (IT) trastuzumab treatment in January 2012. (B) Decreased size of the brain parenchymal metastatic mass and leptomeningeal nodules was documented after 8 months of IT trastuzumab therapy in September 2012, compared with brain MRI at the beginning of IT trastuzumab. (C) No evidence of newly developed enhancing nodules was detected after 18 months of IT trastuzumab therapy in July 2013.

Reference

References

1. Grossman SA, Krabak MJ. Leptomeningeal carcinomatosis. Cancer Treat Rev. 1999; 25:103–19.

2. Jayson GC, Howell A. Carcinomatous meningitis in solid tumours. Ann Oncol. 1996; 7:773–86.

3. Pienkowski T, Zielinski CC. Trastuzumab treatment in patients with breast cancer and metastatic CNS disease. Ann Oncol. 2010; 21:917–24.

4. Zagouri F, Sergentanis TN, Bartsch R, Berghoff AS, Chrysikos D, de Azambuja E, et al. Intrathecal administration of trastuzumab for the treatment of meningeal carcinomatosis in HER2-positive metastatic breast cancer: a systematic review and pooled analysis. Breast Cancer Res Treat. 2013; 139:13–22.

5. Clarke JL, Perez HR, Jacks LM, Panageas KS, Deangelis LM. Leptomeningeal metastases in the MRI era. Neurology. 2010; 74:1449–54.

6. Baselga J, Perez EA, Pienkowski T, Bell R. Adjuvant trastuzumab: a milestone in the treatment of HER-2-positive early breast cancer. Oncologist. 2006; 11 Suppl 1:4–12.

7. Pestalozzi BC, Brignoli S. Trastuzumab in CSF. J Clin Oncol. 2000; 18:2349–51.

8. Stemmler HJ, Schmitt M, Willems A, Bernhard H, Harbeck N, Heinemann V. Ratio of trastuzumab levels in serum and cerebrospinal fluid is altered in HER2-positive breast cancer patients with brain metastases and impairment of blood-brain barrier. Anticancer Drugs. 2007; 18:23–8.

9. Le Rhun E, Taillibert S, Chamberlain MC. Carcinomatous meningitis: Leptomeningeal metastases in solid tumors. Surg Neurol Int. 2013; 4(Suppl 4):S265–88.

10. Mir O, Ropert S, Alexandre J, Lemare F, Goldwasser F. High-dose intrathecal trastuzumab for leptomeningeal metastases secondary to HER-2 overexpressing breast cancer. Ann Oncol. 2008; 19:1978–80.

11. Hofer S, Mengele K, Stemmler HJ, Schmitt M, Pestalozzi B. Intrathecal trastuzumab: dose matters. Acta Oncol. 2012; 51:955–6.