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Journal of Neuro-Oncology

, Volume 57, Issue 3, pp 231–239 | Cite as

An Open Label Trial of Sustained-release Cytarabine (DepoCyt™) for the Intrathecal Treatment of Solid Tumor Neoplastic Meningitis

  • Kurt A. Jaeckle
  • Tracy Batchelor
  • Steven J. O'Day
  • Surasak Phuphanich
  • Pamela New
  • Glenn Lesser
  • Allen Cohn
  • Mark Gilbert
  • Robert Aiken
  • Deborah Heros
  • Lisa Rogers
  • Eric Wong
  • Dorcas Fulton
  • John C. Gutheil
  • Said Baidas
  • Julia M. Kennedy
  • Warren Mason
  • Paul Moots
  • Christy Russell
  • Lode J. Swinnen
  • Stephen B. Howell
Article

Abstract

Drugs currently available for intrathecal administration are cleared rapidly from the CSF. DepoCyt is a slow-release formulation of cytarabine that maintains cytotoxic concentrations of free cytarabine in the CSF for >14 days following a single injection. DepoCyt was administered to 110 patients with a diagnosis of neoplastic meningitis based on either a positive CSF cytology (76) or neurologic and CT or MRI scan findings sufficient to document neoplastic meningitis (34). Patients were treated with DepoCyt 50 mg every 2 weeks for 1 month of induction therapy by either lumbar puncture (LP) or intraventricular (IVT) injection. Patients without neurologic progression were candidates to receive an additional 3 months of consolidation therapy. All patients received dexamethasone 4 mg BID on days 1–5 of each cycle. Median time to neurologic progression was 55 days; median overall survival was 95 days. Among the 76 patients with a positive CSF cytology at baseline, 70 were evaluable for response, and of this group19 (27%) attained the criteria for response (cytologic response in the absence of neurologic progression). The most important adverse events were headache and arachnoiditis. When drug-related, these were largely low grade, transient, and reversible. Drug-related grade 3 headache occurred on 4% of cycles; grade 3 or 4 arachnoiditis occurred on 6% of cycles. No cumulative toxicity was observed. DepoCyt injected once every 2 weeks produced a response-rate comparable to that previously reported for methotrexate given twice a week. The once in every 2-week-dosing interval offers an advantage over conventional schedules (2–3 doses/week) used for other agents available for intrathecal injection.

neoplastic meningitis intrathecal cytarabine liposome cerebrospinal fluid 

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References

  1. 1.
    Freilich R, Seidman A, DeAngelis L: Central nervous system progression of metastatic breast cancer in patients treated with paclitaxel. Cancer 76: 232-236, 1995Google Scholar
  2. 2.
    Hitchins RN, Bell DR, Woods RL, Levi JA: A prospective randomized trial of single-agent versus combination chemotherapy in meningeal carcinomatosis. J Clin Oncol 5: 1655-1662, 1987Google Scholar
  3. 3.
    Rosen ST, Aisner J, Makuch RW, Matthews MJ, Ihde DC, Whitacre M, Glatstein EJ, Wiernik PH, Lichter AS, Bunn PA, Jr.: Carcinomatous leptomeningitis in small cell lung cancer: a clinicopathologic review of the national cancer institute experience. Am J Med 61: 45-53, 1982Google Scholar
  4. 4.
    Nugent JL, Bunn PA, Matthews MJ, Ihde DC, Cohen MH, Gazdar A, Minna: CNS metastases in small cell bronchogenic carcinoma: increasing frequency and changing pattern with lengthening survival. Cancer 44: 1885-1893, 1979Google Scholar
  5. 5.
    Yap HY, Yap BS, Tashima CK, DiStefano A, Blumenshein: Meningeal carcinomatosis in breast cancer. Cancer 42: 283-286, 1978Google Scholar
  6. 6.
    Shapiro WR, Posner KB, Ushio Y, Chernik NL, Young: Treatment of meningeal neoplasms. Cancer Treat Rep 61: 733-743, 1977Google Scholar
  7. 7.
    Balis FM, Poplack DG: Central nervous pharmacology of anti-leukemic drugs. Amer J Ped Hem/Oncol 11: 74-86, 1989Google Scholar
  8. 8.
    Strother DR, Glynn-Barnhart A, Kovnar E, Gregory RE, Murphy: Variability in the disposition of intraventricular methotrexate: a proposal for rational dosing. J Clin Oncol 7: 1741-1747, 1989Google Scholar
  9. 9.
    Zimm S, Collins JM, Miser J, Chatterji D, Poplack: Cytosine arabinoside cerebrospinal fluid kinetics. Clin Pharmacol Ther 35: 826-830, 1984Google Scholar
  10. 10.
    Shapiro WR, Young DF, Mehta BM: Methotrexate distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections. New Engl J Med 293: 161-166, 1975Google Scholar
  11. 11.
    Bleyer WA, Poplack DG, Simon RM: 'Concentration × Time' methotrexate via a subcutaneous reservoir: a less toxic regimen for intraventricular chemotherapy of central nervous system neoplasms. Blood 51: 835-842, 1978Google Scholar
  12. 12.
    Merriman R, Hertel L, Schultz R, Houghton P, Houghton J, Rutherford P, Tanzer L, Boder G, GrindeyG: Comparison of the antitumor activity of gemcitabine and ara-C in a panel of human breast, colon, lung and pancreatic xenograft models. Invest New Drugs 14: 243-247, 1996Google Scholar
  13. 13.
    Davis HL, Jr., Rochlin DB, Weiss AJ, Wilson WL, Andrews NC, Madden R, Sedransk N: Cytosine arabinoside (NSC 63878) toxicity and antitumor activity in human solid tumors. Oncol 29: 190-200, 1974Google Scholar
  14. 14.
    Frei E III, Bickers JN, Hewlett JS, Lane M, Leary WV, Talley RW: Dose schedule and antitumor studies of arabinosyl cytosine (NSC 63878). Cancer Res 29: 1325-1332, 1969Google Scholar
  15. 15.
    Kim S, Khatibi S, Howell SB, McCully C, Balis FM, Poplack DG: Prolongation of drug exposure in cerebrospinal fluid by encapsulation into DepoFoam. Cancer Res 53: 1596-1598, 1993Google Scholar
  16. 16.
    Kim S, Kim DJ, Geyer MA, Howell SB: Multivesicular liposomes containing 1-beta-D-arabinofuranosylcytosine for slow-release intrathecal therapy. Cancer Res 47: 3935-3937, 1987Google Scholar
  17. 17.
    Kim S, Chatelut E, Kim JC, Howell SB, Cates C, Kormanik PA, Chamberlain MC: Extended CSF cytarabine exposure following intrathecal administration of DTC 101. J Clin Oncol 11: 2186-2193, 1993Google Scholar
  18. 18.
    Glantz M, Jaeckle KA, Chamberlain MC, Phuphanich S, Recht L, Swinnen LJ, Maria B, LaFollette S, Schumann GB, Cole BF, Howell: A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors. Clinical Cancer Res 5: 3394-3402, 1999Google Scholar
  19. 19.
    Glantz M, LaFollette S, Jaeckle K, Shapiro W, Swinnen L, Rozental J, Phuphanich S, Rogers L, Gutheil J, Batchelor T, Lyter D, Chamberlain M, Maria B, Schiffer C, Bashir R, Thomas D., Cowens W, Howell: A randomized trial of a slow-release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis. J Clin Oncol 17: 3110-3116, 1999Google Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Kurt A. Jaeckle
    • 1
  • Tracy Batchelor
    • 2
  • Steven J. O'Day
    • 3
  • Surasak Phuphanich
    • 4
  • Pamela New
    • 5
  • Glenn Lesser
    • 6
  • Allen Cohn
    • 7
  • Mark Gilbert
    • 8
  • Robert Aiken
    • 9
  • Deborah Heros
    • 10
  • Lisa Rogers
    • 11
  • Eric Wong
    • 12
  • Dorcas Fulton
    • 13
  • John C. Gutheil
    • 14
  • Said Baidas
    • 15
  • Julia M. Kennedy
    • 16
  • Warren Mason
    • 17
  • Paul Moots
    • 18
  • Christy Russell
    • 19
  • Lode J. Swinnen
    • 20
  • Stephen B. Howell
    • 21
  1. 1.Mayo ClinicJacksonvilleUSA
  2. 2.Dept. of Neuro-OncologyMassachusetts General HospitalBostonUSA
  3. 3.John Wayne Cancer InstituteSanta MonicaUSA
  4. 4.Dept. of Neuro-OncologyMoffitt Cancer CenterTampaUSA
  5. 5.Dept. of MedicineUniversity of TexasSan AntonioUSA
  6. 6.Wake Forest University Comprehensive Cancer CenterWinston-SalemUSA
  7. 7.University of Colorado Medical CenterDenverUSA
  8. 8.Emory University HospitalAtlantaUSA
  9. 9.Thomas Jefferson University HospitalPhiladelphiaUSA
  10. 10.Mt. Sinai Comprehensive Cancer CenterMiami BeachUSA
  11. 11.Wayne State University Health CenterDetroitUSA
  12. 12.Beth Israel Deaconess Medical CenterBrooklineUSA
  13. 13.Cross Cancer InstituteEdmontonCanada
  14. 14.Sidney Kimmel Cancer CenterSan DiegoUSA
  15. 15.Georgetown University Medical CenterWashington, DCUSA
  16. 16.Frankford Hospital Cancer CenterPhiladelphiaUSA
  17. 17.Ontario Cancer InstituteTorontoCanada
  18. 18.Vanderbilt University Medical CenterNashvilleUSA
  19. 19.Norris Cancer CenterLos AngelesUSA
  20. 20.Loyola University of ChicagoMaywoodUSA
  21. 21.University of CaliforniaSan Diego, La JollaUSA

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