Histology is a dominant factor in determining outcome in patients with recurrent glioma enrolled onto phase II trials. Future trials should be designed with separate histology strata.

Eective anti cancer strategies necessitate the use of agents that target tumor cells rather than normal tissues. In this study, we constructed a tumor-selective adenovirus, D24, that carries a 24-bp deletion in the E1A region responsible for binding Rb protein. Immunoprecipitation analyses veri®ed that this deletion rendered D24 unable to bind the Rb protein. However, titration experiments in 293 cells demonstrated that the D24 adenovirus could replicate in and lyse cancer cells with great eciency. Lysis of most human glioma cells was observed within 10 ± 14 days after infection with D24 at 10 PFU/cell. In vivo, a single dose of the D24 virus induced a 66.3% inhibition (P50.005) and multiple injections, an 83.8% inhibition (P50.01) of tumor growth in nude mice. However, normal ®broblasts or cancer cells with restored Rb activity were resistant to the D24 adenovirus. These results suggest that the E1A-mutant D24 adenovirus may be clinically and therapeutically useful against gliomas and possibly other cancers with disrupted Rb pathway. Oncogene (2000) 19, 2 ± 12.

A randomized, multicentre, open-label, phase II study compared temozolomide (TMZ), an oral second-generation alkylating agent, and procarbazine (PCB) in 225 patients with glioblastoma multiforme at first relapse. Primary objectives were to determine progression-free survival (PFS) at 6 months and safety for TMZ and PCB in adult patients who failed conventional treatment. Secondary objectives were to assess overall survival and health-related quality of life (HRQL). TMZ was given orally at 200 mg/m 2 /day or 150 mg/m 2 /day (prior chemotherapy) for 5 days, repeated every 28 days. PCB was given orally at 150 mg/m 2 /day or 125 mg/m 2 /day (prior chemotherapy) for 28 days, repeated every 56 days. HRQL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 [+3]) and the Brain Cancer Module 20 (BCM20). The 6-month PFS rate for patients who received TMZ was 21%, which met the protocol objective. The 6-month PFS rate for those who received PCB was 8% ( P = 0.008, for the comparison). Overall PFS significantly improved with TMZ, with a median PFS of 12.4 weeks in the TMZ group and 8.32 weeks in the PCB group ( P = 0.0063). The 6-month overall survival rate for TMZ patients was 60% vs. 44% for PCB patients ( P = 0.019). Freedom from disease progression was associated with maintenance of HRQL, regardless of treatment received. TMZ had an acceptable safety profile; most adverse events were mild or moderate in severity. © 2000 Cancer Research Campaign