Journal of Neuro-Oncology 44: 59–64, 1999. © 1999 Kluwer Academic Publishers. Printed in the Netherlands. Clinical Study Phase II study of weekly dose-intensified cisplatin chemotherapy with oral etoposide in recurrent glioma M.J. van den Bent 1 , L. Pronk 2 , P.A.E. Sillevis Smitt 1 , Ch.J. Vecht 1 , F.A.L.M. Eskens 2 and J. Verweij 2 1 Department of Neuro-Oncology and 2 Department of Medical Oncology, Daniel den Hoed Cancer Clinic and University Hospital Rotterdam, the Netherlands Key words: recurrent, glioma, astrocytoma, chemotherapy, cisplatin, etoposide Summary Background. In most patients with recurrent glioma chemotherapy is the only remaining treatment option. In general results of chemotherapy in these patients are poor, and trials on new regimens are indicated. Because relatively good results have been achieved with combinations of platin compounds and etoposide, we investigated a dose-intensified cisplatin regimen with oral etoposide. Methods. Eligible patients, with recurrent glioma after surgery and radiation therapy were treated with two four week-cycles with cisplatin 70 mg/m 2 on days 1, 8 and 15, combined with oral etoposide 50 mg daily on days 1–15. In responding or stabilized patients, treatment was continued with six four week-cycles of oral etoposide 50 mg/m 2 on days 1–21. Toxicity was assessed using the NCI Common Toxicity Criteria, a 50% decrease in contrast enhancing area on MRI scan was considered a partial response. Time to progression was measured from the start of chemotherapy. Results. Sixteen patients were included, 11 were progressive during or immediately after the induction cycles. Two patients achieved a partial response with a time to progression of 42 and 58 weeks. Three patients were stable for 11, 14 and 15 weeks respectively. Toxicity was modest. Discussion. This dose-intensified cisplatin regimen did not result in a significant number of objective responses and even the number of ‘stable disease’ was small. Given the low response rate of this intensive treatment, we consider this intensive regimen inappropriate for these patients. Introduction For most patients with recurrent glioma after surgery and radiation therapy the only remaining treatment modality is chemotherapy. Unfortunately, the response rates of high grade gliomas to chemotherapy are poor. However, several small studies on combinations of etoposide and either carboplatin or cisplatin reported 13–21% objective response rates (complete (CRs) and partial responses (PRs)), with 45–53% of patient responding or stabilized (Table 1). Median time to pro- gression (MTP) in these studies was 28– 42.5 weeks, and 19–32% of patients were free from progression at six months [1–3]. These figures compare favorably with single agent studies on etoposide, carboplatin and cisplatin [4–8]. At our institute a weekly dose-intensified cisplatin schedule combined with oral etoposide has exten- sively been explored [9–12]. With this schedule a cis- platin dose intensity of 52.5–60 mg/m 2 per week can be achieved in most patients, with acceptable toxic- ity. Responding and stabilized patients receive main- tenance therapy with oral etoposide for six months. With this regimen, a response rate of 52% of stage III non-small cell lung carcinoma, of 32% grade IV NSCL and of 24% of patients with mesothelioma were observed. Because of the relatively favorable results obtained by others in recurrent glioma with varying combinations of platin compounds and etopo- side in standard dosages, we investigated this dose- intensified cisplatin regimen in patients with recurrent glioma.