Intra-carotid chemo (ICC) followed by radiation (RT) with concomitant temozolamide (TMZ) and subsequent maintenance TMZ therapy in patients (pts) with glioblastoma multiforme (GBM)

1554 Background: Glioblastoma multiforme is one of the most resistant malignant tumors. Surgery provides only temporary, palliative relief. Radiation therapy affords additional, though short, benefit. Systemic, intravenous and/or oral chemotherapy with nitrosoureas and TMZ, increases survival only slightly. Median survival (MS) after all these modalities incorporated remains unimpressive, less than 14 months. Intracarotid chemotherapy with cisplatin and VP-16, a standard treatment at Stony Brook University Hospital since 1999, prior to RT, results in MS of 20 months. A year later we added TMZ as a part of standard treatment with or without ICC in patients with GBM. Provided here is a retrospective analysis of the treatment consisting of surgery, ICC, RT with concomitant TMZ followed by 2 years of TMZ maintenance. Methods: Fifteen patients with pathologically confirmed, newly diagnosed GBM were treated from year 2000 to 2005; 11 men; median age 53 (range 25-68); 80% with PS over 70. They underwent a surgical procedure (5 near total) followed by ICC with cisplatin 60 mg/m2 and VP-16 40 mg/m2 every 3 weeks for total of 3 cycles. Subsequently they received TMZ 75 mg/m2/day orally, concomitantly with RT 6120–6300 cGY, followed a month later by maintenance therapy with TMZ 200 mg/m2/ daily for 5 days out of each month for 2 years or until progression. Results: Fourteen pts.are being evaluated (one too early), all have survived at least 12 months.One-year PFS is 79%. Median time to progression is 19.5 months; MS is 25 months with a range of 12-48 months. Toxicity is limited to nausea and vomiting mainly grade 1-2; only 1 patient experienced grade 3 vomiting with subsequent TMZ maintenance dose reduction by about 10%. Conclusions: Surgery followed by ICC, then combination of RT + TMZ followed by maintenance TMZ therapy seems to be more effective in improving patient survival than surgery, ICC and RT as reported previously by us in pts with GBM (Cancer 2000; 10:2350–6). This treatment has been well tolerated. No significant financial relationships to disclose.

Uniformity of intracarotid drug distribution with diastole-phased pulsed infusion

✓ Drug streaming has been implicated in the development of focal necrotic lesions in perfused tissues following intracarotid chemotherapy of brain tumors at low infusion rates. The narrow infusate path characteristic of streaming within laminar blood flow is not observed at high infusion rates such as are typical in contrast injection for angiography. By periodically pulsing the infusate at a high rate, the mechanisms of rapid mixing can be exploited while retaining the practicality of low average infusion rates. This in vitro study demonstrates the effects of the pulse-controlling parameters and the catheter characteristics and placement on mixing effectiveness. An internal carotid artery model including eight cerebral branches was infused with dye through various indwelling catheters, and individual branch effluents were collected and analyzed spectrophotometrically for dye concentration. While catheter placement dominates the factors that control infusate distribution, judicious selection of the pulse parameters can alleviate that dependence. A primary advantage is gained by phasing the pulse to occur during that period of the cardiac cycle when the blood flow is lowest at the injection site. The data clearly showed that diastole-phased pulsed infusions are highly effective in producing a uniform infusate distribution at low average infusion rates.