Efficacy of Slow Rate Ventriculolumbar Perfusion Chemotherapy for Leptomeningeal Carcinomatosis: Interim Result of a Phase II Study

BACKGROUND: To evaluate the efficacy of modified ventriculolumbar perfusion (VLP) chemotherapy with methotrexate on leptomeningeal carcinomatosis in terms of symptomatic response and side effects. METHODS: Previous infusion rate of 20 mL/h was reduced to 15 mL/h for the purpose of decreasing constitutional side effects of VLP such as nausea/vomiting, insomnia and confusion. The primary outcome was the response rate of increased intracranial pressure (ICP), and the secondary outcome was the occurrence of side effects compared to previous 20 mL/h trial. This interim analysis to validate the reduced infusion rate is not to affect the original effect of VLP chemotherapy. RESULTS: All forty-seven patients were enrolled including 22 patients with increased ICP. Thirteen patients out of these (59%) got normalized ICP after VLP chemotherapy. Moderate to severe (grade 2–3) confusion was observed in 3 patients (6%) and it was significantly reduced compared to those (23%) in the VLP 20 mL/h (p=0.017). Grade 2–3 nausea/vomiting was also reduced from 64% to 45% but failed to reach statistical significance (p=0.08). Median overall survival (OS) was 5.3 months (95% confidence interval, 3.55–7.05) and patients OS, who received maintenance VLP was significantly prolonged compared to patients who underwent induction VLP only (5.8 vs. 3.4 months, p=0.025). CONCLUSION: VLP of reduced perfusion rate (15 mL/h) showed compatible control rate of increased ICP at this interim analysis. Decreased moderate to severe side effects and prolonged OS in patients received maintenance VLP encourage us to evaluate the effectiveness of this trial further.

Temozolomide Salvage Chemotherapy for Recurrent Anaplastic Oligodendroglioma and Oligo-Astrocytoma

OBJECTIVE: To evaluate the efficacy of temozolomide (TMZ) chemotherapy for recurrent anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA). METHODS: A multi-center retrospective trial enrolled seventy-two patients with histologically proven AO/AOA who underwent TMZ chemotherapy for their recurrent tumors from 2006 to 2010. TMZ was administered orally (150 to 200 mg/m2/day) for 5 days per 28 days until unacceptable toxicity occurred or tumor progression was observed. RESULTS: TMZ chemotherapy cycles administered was median 5.3 (range, 1-41). The objective response rate was 24% including 8 cases (11%) of complete response and another 23 patients (32%) were remained as stable disease. Severe side effects (> or =grade 3) occurred only in 9 patients (13%). Progression-free survival (PFS) of all patients was a median 8.0 months (95% confidence interval, 6.0-10.0). The time to recurrence of a year or after was a favorable prognostic factor for PFS (p<0.05). Overall survival (OS) was apparently differed by the patient's histology, as AOA patients survived a median OS of 18.0 months while AO patients did not reach median OS at median follow-up of 11.5 months (range 2.7-65 months). Good performance status of Eastern Cooperative Oncology Group 0 and 1 showed prolonged OS (p<0.01). CONCLUSION: For recurrent AO/AOA after surgery followed by radiation therapy, TMZ could be recommended as a salvage therapy at the estimated efficacy equal to procarbazine, lomustine, and vincristine (PCV) chemotherapy at first relapse. For patients previously treated with PCV, TMZ is a favorable therapeutic option as 2nd line salvage chemotherapy with an acceptable toxicity rate.