Salvage Chemotherapy with CPT-11 for Recurrent Glioblastoma Multiforme
- 74 Downloads
Background: A prospective Phase II study of CPT-11 in adult patients with recurrent supratentorial glioblastoma multiforme (GBM).
Methods: Forty patients (25 men, 15 women) ages 32–71 years (median 59), with recurrent GBM were treated. All patients had previously been treated with surgery and involved field radiotherapy (median dose 60 Gy; range 59–60). Additionally, all patients were treated with adjuvant chemotherapy (BCNU in 20, PCV in 18, Procarbazine in 2). Twenty-five patients (62%) were on anticonvulsants (phenytoin in 15, carbamazepine in 10) and 26 patients (65%) were on dexamethasone. Recurrent disease was defined by neuroradiographic disease progression (>25% increase in tumor dimensions) using gadolinium-enhanced MR imaging. The starting dose of CPT-11 was 400 mg/m2 followed in three weeks by 500 mg/m2, operationally defined as one cycle. At week 6, all patients were evaluated with MRI and neurological examination.
Results: All patients were evaluable. Two doses (one cycle) of CPT-11 were administered to all patients. CPT-11-related toxicity included: diarrhea (16 patients, 40%); thrombocytopenia (9 patients, 23%); and neutropenia (6 patients, 15%). No patient required transfusion nor was treatment for neutropenic fever required. No treatment-related deaths were observed. All patients demonstrated progressive disease following one cycle of CPT-11.
Conclusions: The lack of response to CPT-11 in this patient group with recurrent GBM suggests either CPT-11 has minimal activity or CPT-11 doses/schedule utilized in this study were sub-optimal. The latter is supported by the modest toxicity seen in this study and the previously documented enhanced clearance of CPT-11 in patients on anticonvulsants and dexamethasone.
Unable to display preview. Download preview PDF.
- 1.Black PMcL: Brain tumors, part I. NEJM 324(21): 1471-1476, 1991Google Scholar
- 2.Black PMcL: Brain tumors, part II. NEJM 324(22): 1555-1564, 1991Google Scholar
- 3.DeAngelis LM: Brain tumors. NEJM 344(2): 114-123, 2001Google Scholar
- 4.Kornblith PD, Welch WC, Bradley MK: The future of therapy for glioblastoma. Surg Neurol 39: 538-543, 1993Google Scholar
- 5.Rostomily RC, Spence AM, Duong D: Multi-modality management of recurrent adult malignant gliomas: results of a phase 2 multi-agent chemotherapy study and analysis of cytoreductive surgery. Neurosurgery 35: 378-388, 1994Google Scholar
- 6.Cokgor I, Akabani G, Kuan CT, Friedman HS, Friedman AH, Coleman RE, McLendon RE, Bigner SH, Zhao XG, Garcia-Turner AM, Pegram CN, Wikstrand CJ, Shafman TD, Herndon JE, Provenzale JM, Zalutsky MR, Bigner DD: Phase 1 trial results of iodine-131 labeled antitenascin monoclonal antibody 81c6 treatment of patients with newly diagnosed malignant gliomas. J Clin Oncol 18(22): 3862-3872, 2000Google Scholar
- 7.Hall WA, Djalilian HR, Sperduto PW, Cho KH, Gerbi BJ, Gibbons JP, Rohr M, Clark HB: Stereotactic radiosurgery for recurrent malignant gliomas. J Clin Oncol 13: 1642-1648, 1995Google Scholar
- 8.Salcman M: Resection and re-operation in neuro-oncology: rationale and approach. Neurol Clin 3: 831-842, 1985Google Scholar
- 9.Suh JH, Barnett GH: Brachytherapy for brain tumor. Hematol Oncol Clin North Am 13: 635-640, 1999Google Scholar
- 10.Yung WKA, Mechtler L, Gleason MJ: Intravenous carboplatin for recurrent malignant gliomas: a phase II study. J Clin Oncol 9: 860, 1991Google Scholar
- 11.Brem H, Piantadosi S, Burger PC, Walker M, Selker M, Vick NA, Black K, Sisti M, Brem S, Mohr P, Morawetz R, Schold SC: Placebo-controlled trial of safety and efficacy of intra-operative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. Lancet 345(8956): 1008-1012, 1995Google Scholar
- 12.Friedman HS, Kerby T, Calvert H: Temozolomide and treatment of malignant glioma. Clin Cancer Res 6: 2585-2597, 2000Google Scholar
- 13.Kaba SE, Kyritsis AP, Conrad C, Gleason MJ, Newman R, Levin VA, Yung WKA: The treatment of recurrent cerebral gliomas with all trans-retinoic acid. J Neuro-Oncol 34: 145-151, 1997Google Scholar
- 14.Longee DC, Friedman HS, Albright RE, Burger PC, Oakes WJ, Moore JO, Schold SC: Treatment of patients with recurrent gliomas with cyclophosphamide and vincristine. J Neurosurg 72: 583-588, 1990Google Scholar
- 15.Newton HB, Junck L, Bromberg J: Procarbazine chemotherapy in the treatment of recurrent malignant astrocytomas after radiation and nitrosourea failure. Neurology 40: 1743-1746, 1990Google Scholar
- 16.Warnick RE, Prados MD, Mack EE: A phase 2 study of intravenous carboplatin for the treatment of recurrent gliomas. J Neuro-Oncol 19: 69-74, 1994Google Scholar
- 17.Friedman HS, Petros WP, Friedman AH, Schaaf LJ, Kerby T, Lawyer J, Parry M, Houghton PJ, Lovell S, Rasheed K, Cloughsey T, Stewart ES, Colvin OM, Provenzale JM, McLendon RE, Bigner DD, Cokgor I, Haglund M, Rich J, Ashley D, Malczyn J, Elfring GL, Miller LL: Irinotecan therapy in adults with recurrent or progressive malignant glioma. J Clin Oncol 17: 1516-1525, 1999Google Scholar
- 18.Vanhoefer U, Harstrick A, Achterrath W, Cao S, Seeber S, Rustum Y: Irinotecan in the treatment of colorectal cancer: clinical overview. J Clin Oncol 19: 1501-1518, 2001Google Scholar
- 19.Macdonald DR, Cascino TL, Schold Jr SC, Cairncross JG: Response criteria for Phase II studies supratentorial malignant glioma. J Clin Oncol 8(7): 1277-1280, 1990Google Scholar
- 20.Gehan EA: The determination of the number of newpatients required in a preliminary and follow-up trial of a new chemotherapeutic agent. J Chronic Dis 13: 346-353, 1961Google Scholar
- 21.Wong ET, Hess KR, Gleason MJ, Jaeckle KA, Kyritsis AP, Prados MD, Levin VA, Yung WKA: Outcomes and prognostic factors enrolled onto phase 2 clinical trials. J Clin Oncol 17: 2572-2578, 1999Google Scholar
- 22.Levin VA, Silver P, Hannigan J, Wara WM, Gutin PH, Davis RL, Wilson CB: Superiority of post-radiotherapy adjuvant chemotherapy with CCNU, procarbazine and vincristine (PCV) over BCNU for anaplastic gliomas: NCOG 6G61 final report. Int J Radiat Oncol Biol Phys 18(2): 321-324, 1990Google Scholar
- 23.Saltz LB, Cox JV, Blanke C, Rosen LS, Fehrenbacher L, Moore MJ, Maroun JA, Ackland SP, Locker PK, Pirotta N, Elfring GL, Miller LL: Irinotecan plus Fluorouracil and Leucovorin for metastatic colorectal cancer. NEJM 343: 905-914, 2000Google Scholar
- 24.Fetell MR, Grossman SA, Balmaceda C: Clinical and pharmacologic study of pre-irradiation Taxol administrated as a 96-hour infusion in adults with newly diagnosed glioblastoma multiforme. Proceed ASCO 13: 179 (Abstract), 1994Google Scholar
- 25.Prados M, Kuhn J, Yung WKA, Robbins HI, Fink K, Greenberg H, Junck L, Cloughesy T, Chang S, Fine H, SchiffD, Nicholas MK, Jaeckle KA, Hess K, Wen P: Phase-1 study of CPT-11 given every 3 weeks in patients with recurrent brain tumors, a north American brain tumor consortium study. Neuro-Oncol 2(4): 287-288, 2000Google Scholar