Therapy for patients with high grade astrocytoma using intraarterial chemotherapy and radiation therapy

Abstract

BACKGROUND High grade astrocytomas account for approximately 40% of all primary brain tumors. The median survival is approximately 8–10 months for patients with glioblastoma multiforme and 36 months for patients with anaplastic astrocytoma. The results of systemic chemotherapy in the treatment of brain tumors have been reported to be less than satisfactory, mainly because of the blood‐brain barrier impermeability for chemotherapeutic drugs. Intraarterial chemotherapy has been an attractive alternative with which to overcome this problem. METHODS Eighty‐three patients with high grade astrocytoma (glioblastoma multiforme [63 patients] and anaplastic astrocytoma –[20 patients]) were treated with intraarterial (intracarotid and/or intravertebral) chemotherapy and radiation therapy between 1987 and 1997. Patients received cisplatin, 60 mg/m2, and etoposide, 40 mg/m2. Radiation therapy was delivered either after completion of the chemotherapy or concomitantly with the chemotherapy. RESULTS Thirty‐four of 71 evaluable patients with high grade astrocytoma (48%) responded to the chemotherapy. The median survival for patients with glioblastoma multiforme who received chemotherapy prior to radiation therapy was 20 months versus 7 months for those patients who underwent concomitant chemotherapy/radiation therapy. Patients with anaplastic astrocytoma who received chemotherapy prior to radiation therapy had a median survival of 45 months compared with 12 months for patients who received concomitant chemotherapy/radiation therapy. The toxicity profile has been reported to be mild and well tolerated. CONCLUSIONS Intraarterial chemotherapy for patients with glioblastoma multiforme, delivered prior to radiation therapy, appears to result in a median survival three times longer than that achieved with concomitant chemotherapy/radiation therapy. In addition, patients appear to survive substantially longer than they do after radiation therapy with the addition of systemic chemotherapy. Side effects are reported to be acceptable. Cancer 2000;88:2350–6. © 2000 American Cancer Society.

Efficacy and Toxicity of Postoperative Temozolomide Radiochemotherapy in Malignant Glioma

“…Many groups have tried to increase the efficacy of postoperative radiotherapy by simultaneous radiochemotherapy, either by i.v. infusion of nitrosoureas [1,8,15,25], platinum derivatives [4,24,29], taxanes [11,13,16,28,35] or topotecan [12,17] or by intraarterial infusion [10,14,25,32]. In most of these schemes, chemotherapy was applied only at some days during radiotherapy, and no schedule showed a significant increase in overall survival.…”

“…Several substances have been applied simultaneously to irradiation in order to increase local control. Nitrosoureas, cytarabine (ARA-C) [1,8,15,25], platinum plus etoposide or teniposide [4,24,29] have been used for intravenous or intraarterial [10,14,25,32] infusion during the period of irradiation, but so far, none of these regimens has led to a significant increase in survival.…”

Radiochemotherapy of Malignant Glioma in Adults

“…Likewise, intraarterial chemotherapy showed doubtful efficacy. In the framework of small series, intraarterial chemotherapy in malignant gliomas was accompanied by substantial toxicity [45,49] and led to shorter survival time in one study [106], although another study with a limited patient number showed promising results for intraarterial neoadjuvant cisplatin/ etoposide followed by standard radiotherapy [79].…”

Induction of p53-mediated apoptosis and recovery of chemosensitivity through p53 transduction in human glioblastoma cells by cisplatin

“…Despite innumerable efforts to develop more effective clinical treatment strategies, the median survival time for patients with WHO grade 4 glioma, glioblastoma multiforme, remains at approximately 1 year (1)(2)(3)(4). An important factor contributing to this prognosis is the relative chemoresistance of many gliomas to chemotherapy in general (5)(6)(7). Nonetheless, chemotherapy is the most widely used modality in the management of gliomas (8).…”