Tanja H.
AANS: Sequential Intra-Arterial Chemotherapy Superior To Concurrent Therapy In High-Grade Astrocytomas
By Cameron Johnston
Special to DG News
TORONTO, ON -- April 26, 2001 -- There is a significant difference in outcomes between patients with high-grade astrocytoma who receive chemotherapy in advance of radiation therapy and those who receive concurrent regimens.
And because of the difficulty with most chemotherapeutic agents crossing the blood-brain barrier, it might be that intra-arterial delivery of the chemotherapeutic agents is the preferred mode of treatment.
These findings were presented at the annual meeting of the American Association of Neurological Surgeons in Toronto, Canada, by Dr. Arthur Rosiello, of the department of neurosurgery at the State University of New York at Stony Brook. He outlined the results of a retrospective study which looked at 105 subjects who had received either concurrent or sequential chemoradiation therapy to treat their brain tumors-either glioblastoma multiforme or anaplastic astrocytoma.
The regimens delivered included cisplatin 60 mg/m2 and etoposide 40 mg/m2 for two or three courses before radiation therapy was started. The radiation doses used were 4500 Gy in 180 fractions overall, and specifically, 5580 Gy delivered to the optic chiasm, pituitary and brain stem. The total tumor dose was 6120-6300 Gy.
There were 78 subjects in the study with glioblastoma multiforme and 27 with anaplastic astrocytoma. A total of 58 of the 78 glioblastoma subjects had Karnofsky performance scores of 70 or less. Only 12 patients underwent complete resection and the vast majority of those in the glioblastoma group had only biopsy.
According to Dr. Rosiello, the survival rates for glioblastoma multiforme are extremely poor - in the order of 10 months on average, whereas or anaplastic astrocytoma, the survival rate is somewhat better, at 36 months.
In this study, intra-carotid (IC) arterial injections of cisplatin and etoposide followed by radiation therapy were found to increase survival time three-fold as compared with subjects who were treated with conventional chemotherapy and radiation.
A complete response was defined as a complete normalization of the computed tomography or magnetic resonance imaging scans and/or discontinuation of high dose steroids. Partial response involved at least a 50 percent decrease in tumor size, and stabilization or reduction in steroid dose.
The overall response rate in this study was 49 percent and the overall survival time was 20 months, with a range of 2 to 110 months.
For those receiving sequential therapy, the response rate was 55 percent overall, with a nine percent complete response rate, and a 46 percent partial response rate (P=.001). The median survival was 22 months for those with glioma and 45 months for those with astrocytoma for those receiving sequential therapy.
Patients receiving concurrent therapy had survival that was seven months for those with glioblastoma and 12 months for those with anaplastic astrocytoma. There was a 36 percent overall response rate, although no complete responses were observed.
"Based on the comparison between sequential and concurrent therapy, our major conclusion is that radiation therapy delivered before chemotherapy may compromise the effectiveness of chemotherapy either by affecting tumor vascularity, or altering the chemotherapy pharmacodynamics. It is also possible that radiation causes resistance to develop within the tumors, or encourages more tumor cells to enter the resting state," Dr. Rosiello said
"We feel that IC intra-arterial cisplatin and etoposide are well tolerated with acceptable toxicity. We feel that intra-carotid chemotherapy delivered prior to radiation improves survival of high-grade astrocytoma, despite the negative variables such as age, Karnofsky performance scores, and the extent of resection," he concluded. "We also feel that efficacy and toxicity profiles compare favorably with other established experimental therapies."