Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 2001 Jan;84(2):157–163. doi: 10.1054/bjoc.2000.1574

Intrathecal treatment of neoplastic meningitis due to breast cancer with a slow-release formulation of cytarabine

K A Jaeckle 1, S Phuphanich 1, M J van den Bent 1, R Aiken 1, T Batchelor 1, T Campbell 1, D Fulton 1, M Gilbert 1, D Heros 1, L Rogers 1, S J O'Day 1, W Akerley 1, J Allen 1, S Baidas 1, S Z Gertler 1, H S Greenberg 1, S LaFollette 1, G Lesser 1, W Mason 1, L Recht 1, E Wong 1, M C Chamberlain 1, A Cohn 1, M J Glantz 1, J C Gutheil 1, B Maria 1, P Moots 1, P New 1, C Russell 1, W Shapiro 1, L Swinnen 1, S B Howell 1
PMCID: PMC2363714  PMID: 11161370

Abstract

DepoCyte is a slow-release formulation of cytarabine designed for intrathecal administration. The goal of this multi-centre cohort study was to determine the safety and efficacy of DepoCyte for the intrathecal treatment of neoplastic meningitis due to breast cancer. DepoCyte 50 mg was injected once every 2 weeks for one month of induction therapy; responding patients were treated with an additional 3 months of consolidation therapy. All patients had metastatic breast cancer and a positive CSF cytology or neurologic findings characteristic of neoplastic meningitis. The median number of DepoCyte doses was 3, and 85% of patients completed the planned 1 month induction. Median follow up is currently 19 months. The primary endpoint was response, defined as conversion of the CSF cytology from positive to negative at all sites known to be positive, and the absence of neurologic progression at the time the cytologic conversion was documented. The response rate among the 43 evaluable patients was 28% (CI 95%: 14–41%); the intent-to-treat response rate was 21% (CI 95%: 12–34%). Median time to neurologic progression was 49 days (range 1–515+); median survival was 88 days (range 1–515+), and 1 year survival is projected to be 19%. The major adverse events were headache and arachnoiditis. When drug-related, these were largely of low grade, transient and reversible. Headache occurred on 11% of cycles; 90% were grade 1 or 2. Arachnoiditis occurred on 19% of cycles; 88% were grade 1 or 2. DepoCyte demonstrated activity in neoplastic meningitis due to breast cancer that is comparable to results reported with conventional intrathecal agents. However, this activity was achieved with one fourth as many intrathecal injections as typically required in conventional therapy. The every 2 week dose schedule is a major advantage for both patients and physicians. © 2001 Cancer Research Campaign http://www.bjcancer.com

Keywords: breast cancer, neoplastic meningitis, cytarabine, drug delivery

Full Text

The Full Text of this article is available as a PDF (67.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Balm M., Hammack J. Leptomeningeal carcinomatosis. Presenting features and prognostic factors. Arch Neurol. 1996 Jul;53(7):626–632. doi: 10.1001/archneur.1996.00550070064013. [DOI] [PubMed] [Google Scholar]
  2. Bleyer W. A., Dedrick R. L. Clinical pharmacology of intrathecal methotrexate. I. Pharmacokinetics in nontoxic patients after lumbar injection. Cancer Treat Rep. 1977 Jul;61(4):703–708. [PubMed] [Google Scholar]
  3. Boogerd W., Hart A. A., van der Sande J. J., Engelsman E. Meningeal carcinomatosis in breast cancer. Prognostic factors and influence of treatment. Cancer. 1991 Mar 15;67(6):1685–1695. doi: 10.1002/1097-0142(19910315)67:6<1685::aid-cncr2820670635>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  4. Chamberlain M. C., Kormanik P. A. Prognostic significance of coexistent bulky metastatic central nervous system disease in patients with leptomeningeal metastases. Arch Neurol. 1997 Nov;54(11):1364–1368. doi: 10.1001/archneur.1997.00550230037013. [DOI] [PubMed] [Google Scholar]
  5. Chamberlain M. C., Kormanik P. R. Carcinomatous meningitis secondary to breast cancer: predictors of response to combined modality therapy. J Neurooncol. 1997 Oct;35(1):55–64. doi: 10.1023/a:1005803918194. [DOI] [PubMed] [Google Scholar]
  6. Fizazi K., Asselain B., Vincent-Salomon A., Jouve M., Dieras V., Palangie T., Beuzeboc P., Dorval T., Pouillart P. Meningeal carcinomatosis in patients with breast carcinoma. Clinical features, prognostic factors, and results of a high-dose intrathecal methotrexate regimen. Cancer. 1996 Apr 1;77(7):1315–1323. doi: 10.1002/(SICI)1097-0142(19960401)77:7<1315::AID-CNCR14>3.0.CO;2-4. [DOI] [PubMed] [Google Scholar]
  7. Giannone L., Greco F. A., Hainsworth J. D. Combination intraventricular chemotherapy for meningeal neoplasia. J Clin Oncol. 1986 Jan;4(1):68–73. doi: 10.1200/JCO.1986.4.1.68. [DOI] [PubMed] [Google Scholar]
  8. Glantz M. J., Cole B. F., Recht L., Akerley W., Mills P., Saris S., Hochberg F., Calabresi P., Egorin M. J. High-dose intravenous methotrexate for patients with nonleukemic leptomeningeal cancer: is intrathecal chemotherapy necessary? J Clin Oncol. 1998 Apr;16(4):1561–1567. doi: 10.1200/JCO.1998.16.4.1561. [DOI] [PubMed] [Google Scholar]
  9. Glantz M. J., Jaeckle K. A., Chamberlain M. C., Phuphanich S., Recht L., Swinnen L. J., Maria B., LaFollette S., Schumann G. B., Cole B. F. A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors. Clin Cancer Res. 1999 Nov;5(11):3394–3402. [PubMed] [Google Scholar]
  10. Graham F. L., Whitmore G. F. The effect of-beta-D-arabinofuranosylcytosine on growth, viability, and DNA synthesis of mouse L-cells. Cancer Res. 1970 Nov;30(11):2627–2635. [PubMed] [Google Scholar]
  11. Grant R., Naylor B., Greenberg H. S., Junck L. Clinical outcome in aggressively treated meningeal carcinomatosis. Arch Neurol. 1994 May;51(5):457–461. doi: 10.1001/archneur.1994.00540170033013. [DOI] [PubMed] [Google Scholar]
  12. Grossman S. A., Finkelstein D. M., Ruckdeschel J. C., Trump D. L., Moynihan T., Ettinger D. S. Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. Eastern Cooperative Oncology Group. J Clin Oncol. 1993 Mar;11(3):561–569. doi: 10.1200/JCO.1993.11.3.561. [DOI] [PubMed] [Google Scholar]
  13. Hitchins R. N., Bell D. R., Woods R. L., Levi J. A. A prospective randomized trial of single-agent versus combination chemotherapy in meningeal carcinomatosis. J Clin Oncol. 1987 Oct;5(10):1655–1662. doi: 10.1200/JCO.1987.5.10.1655. [DOI] [PubMed] [Google Scholar]
  14. Jayson G. C., Howell A., Harris M., Morgenstern G., Chang J., Ryder W. D. Carcinomatous meningitis in patients with breast cancer. An aggressive disease variant. Cancer. 1994 Dec 15;74(12):3135–3141. doi: 10.1002/1097-0142(19941215)74:12<3135::aid-cncr2820741212>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
  15. Kim S., Chatelut E., Kim J. C., Howell S. B., Cates C., Kormanik P. A., Chamberlain M. C. Extended CSF cytarabine exposure following intrathecal administration of DTC 101. J Clin Oncol. 1993 Nov;11(11):2186–2193. doi: 10.1200/JCO.1993.11.11.2186. [DOI] [PubMed] [Google Scholar]
  16. Nakagawa H., Murasawa A., Kubo S., Nakajima S., Nakajima Y., Izumoto S., Hayakawa T. Diagnosis and treatment of patients with meningeal carcinomatosis. J Neurooncol. 1992 May;13(1):81–89. doi: 10.1007/BF00172949. [DOI] [PubMed] [Google Scholar]
  17. Ongerboer de Visser B. W., Somers R., Nooyen W. H., van Heerde P., Hart A. A., McVie J. G. Intraventricular methotrexate therapy of leptomeningeal metastasis from breast carcinoma. Neurology. 1983 Dec;33(12):1565–1572. doi: 10.1212/wnl.33.12.1565. [DOI] [PubMed] [Google Scholar]
  18. Shapiro W. R., Young D. F., Mehta B. M. Methotrexate: distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections. N Engl J Med. 1975 Jul 24;293(4):161–166. doi: 10.1056/NEJM197507242930402. [DOI] [PubMed] [Google Scholar]
  19. Zimm S., Collins J. M., Miser J., Chatterji D., Poplack D. G. Cytosine arabinoside cerebrospinal fluid kinetics. Clin Pharmacol Ther. 1984 Jun;35(6):826–830. doi: 10.1038/clpt.1984.120. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES