Journal of Neuro-Oncology

, Volume 44, Issue 2, pp 137–145 | Cite as

Phase II Studies of RMP-7 and Carboplatin in the Treatment of Recurrent High Grade Glioma

  • A. Gregor
  • M. Lind
  • H. Newman
  • R. Grant
  • D.M. Hadley
  • T. Barton
  • C. Osborn


The selective bradykinin analogue, RMP-7, transiently increases the permeability of the blood brain barrier and the delivery of hydrophilic agents into brain tumours. In 87 recurrent glioma patients (WHO Grade III/IV, median age 46, Karnofsky 70%) clinical and Magnetic Resonance Imaging (MRI) responses to i.v. cycles (q 28 days) of RMP-7 (300 ng/kg given as a 10 min infusion) and carboplatin (AUC 4-9) were assessed. 45 of these patients were chemotherapy naive (CN-RMP) and 42 had received one prior course of chemotherapy (CP-RMP). Neurological impairment, performance status and steroid use were measured prior to dosing at each cycle and tumour volume by 3-D MRI at the end of cycles 2, 4, 6, 9 and 12. Clinical evaluation of response demonstrated that 61% of CN-RMP patients were either stable or improved whilst this was 39% for CP-RMP patients, of which 37% and 8% improved respectively. Radiological evaluation showed 79% of CN-RMP patients were either stable, partial or complete responses and 24% for CP-RMP patients, of which 32% and 5% were CR or PR respectively.

The median duration of response was 30.3 weeks in CN-RMP patients and 19.6 weeks in the CP-RMP group. Lack of response was associated with substantial baseline tumour volume. Drug toxicity was as previously reported for carboplatin. 11 patients had treatment-associated transient focal seizures. These results indicate that RMP-7 and carboplatin have significant activity in recurrent malignant glioma following radiotherapy.

glioma RMP-7 carboplatin 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Bleehen NM, Stenning SP on behalf of the Medical Research Council Brain Tumour Working Party: A medical research council trial of two radiotherapy doses in the treatment of grades 3 and 4 astrocytoma. Brit J Cancer 64: 769-774, 1991Google Scholar
  2. 2.
    Levin VA, Edwards MS, Wright DC, Seager ML, Schimberg TP, Townsend JJ, Wilson CB: Modified procarbazine, CCNU and vincristine (PCV 3) combination chemotherapy in the treatment of malignant brain tumours. Cancer Treatment Reports 64: 203, 1980Google Scholar
  3. 3.
    Fine HA: The basis for current treatment recommendations for malignant gliomas. J Neuro-Oncol 20: 111-120, 1994Google Scholar
  4. 4.
    Canetta R, Goodlow J, Smaldone L, Bragman K, Rozencweig M: Pharmacologic characteristics of carboplatin: clinical experience. In: Bunn PA Jr, Canetta R, Ozols RF, Rozencweig M (eds) Carboplatin (JM-8) Current Perspectives and Future Directions. WB Saunders Company, 1990, pp 19-37Google Scholar
  5. 5.
    Jodrell DI, Egorin MJ, Canetta RM, Langenberg P, Goldbloom EP, Burroughs JN, Goodlow JL, Tan S, Wiltshaw E: Relationships between carboplatin exposure and tumor response and toxicity in patients with ovarian cancer. J Clin Oncol 10: 520-528, 1992Google Scholar
  6. 6.
    Doz F, Berens ME, Dougherty DV, Rosenblum ML: Comparison of cytotoxic activities of cisplatin and carboplatin against glioma cell lines at pharmacologically relevant drug exposures. J Neuro-Oncol 11: 27-35, 1991Google Scholar
  7. 7.
    Shinohara C, Matsumoto K, Meada Y, Tada E, Kuriyama M, Adachi H, Ono Y, Higashi H, Furata T, Ohmoto T: Synergistic effect of carboplatin and hyperthermia in rat and human glioma cell lines. Neurol Surg 22, 11: 1029-1033, 1994Google Scholar
  8. 8.
    Dodion P, Sanders C, Georges P, KenisY: In vitro chemosensitivity of brain tumors to cisplatin and its analogues, iproplatin and carboplatin. Cancer Chemother Pharmacol 22: 80-82, 1988Google Scholar
  9. 9.
    Yung WK, Mechtler L, Gleason MJ: Intravenous carboplatin for recurrent malignant glioma: a phase II study. J Clin Oncols 9(5): 860-864, 1991Google Scholar
  10. 10.
    Warnick RE, Prados MD, Mack EE, Chandler KL, Doz F, Rabbitt JE, Malek MK: A phase II study of intravenous carboplatin for the treatment of recurrent glioma. J Neuro-Oncol 19(1): 69-74, 1994Google Scholar
  11. 11.
    Matsukado K, Inamura T, Nakano S, Fukui M, Bartus RT, Black KL: Enhanced tumour uptake of carboplatin and survival in glioma-bearing rats by intracarotid infusion of bradykinin analog, RMP-7. Neurosurgery 39(1): 125-134, 1997Google Scholar
  12. 12.
    Ford J, Osborn C, Barton T, Bleehen NM: Phase I Study of Intravenous RMP-7 with Carboplatin in Patients with Progression of Malignant Glioma. Eur J Cancer (in press)Google Scholar
  13. 13.
    Gehan EA: he determination of the number of patients required in a preliminary and a follow-up trial of a new chemotherapeutic agent. J Chronic Dis 13: 346-353, 1961Google Scholar
  14. 14.
    WHO publication No 48, WHO publications Centre USA, NY 12210, USAGoogle Scholar
  15. 15.
    Calvert AH, Newell DR, Gumbrell LA, O'Reilly S, Burnell M, Boxall FE: Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol 7: 1748-1756, 1989Google Scholar
  16. 16.
    Hopper KD, Kasales CJ, Eggli KD, Belman NM, Potok PS, Ten Have TR, Umlauf MJ, Van Slyke MA, Olt GJ, Close P, Lipton A, Harvey HA, Hartell JS, Go BDM: 2D versus 3D quantitation of tumour response to treatment. In: Quantitative Imaging in Oncology. Proceedings of the 19th LH Gray Conference. Faulkner K, Carey B, Crellin A and Harrison RM (eds). Pub British Institute of Radiology, London, 1996Google Scholar
  17. 17.
    Grant R, Slattery J, Gregor A, Whittle IR: Recording neurological impairment in clinical trials of glioma. J Neuro Oncol 19: 37-49, 1994Google Scholar
  18. 18.
    Clyde Z, Chataway J, Grant R: The Edinburgh Functional Impairment Tests - detecting change in functional impairments in patients with cerebral glioma. Brit J Neurosurg 10(1): 124-125, 1996 (Abstract)Google Scholar
  19. 19.
    Grant R, Collie D: The effect of clinical presentation on management and outcome in patients with high grade glioma. J Neuro Onc 21: 20, 1994 (Abstract)Google Scholar
  20. 20.
    Clyde Z, Grant R: Simple objective tests of limb function and memory are valuable in assessing patients with brain tumors. Neurology A321: PO4.124, 1996 (Abstract)Google Scholar
  21. 21.
    Chataway SJS, Clyde Z, Signorini DF, Whittle IR, Grant R: What represents a clinically significant change in outcome measures following operation for brain tumour? J Neuro-Oncol, 1997 (submitted)Google Scholar
  22. 22.
    Yates JW, Chalmer B, McKegney FP: Evaluation of patients with advanced cancer using the Karnofsky performance status. Cancer 45: 2220-2224, 1980Google Scholar
  23. 23.
    Macdonald DR, Cascino TL, Schold SC, Cairncross JG: Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8(7): 1277-1280, 1990Google Scholar
  24. 24.
    Alvord EC: Patterns of growth of gliomas. American J Neuro Radiology 16: 1013-1017, 1995Google Scholar

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • A. Gregor
    • 1
  • M. Lind
    • 2
  • H. Newman
    • 3
  • R. Grant
    • 1
  • D.M. Hadley
    • 4
  • T. Barton
    • 5
  • C. Osborn
    • 5
  1. 1.Department of Clinical OncologyUniversity of Edinburgh, Western General HospitalEdinburghUK
  2. 2.Department of Clinical Oncology, Northern Centre for Cancer Treatment, Newcastle General HospitalUniversity of Newcastle upon TyneNewcastle upon TyneUK
  3. 3.Department of Clinical OncologyBristol Oncology CentreBristolUK
  4. 4.Department of NeuroradiologyInstitute of Neurological SciencesGlasgowUK
  5. 5.Alkermes Europe Ltd, The QuorumCambridgeUK

Personalised recommendations