A pilot randomised comparison of dexamethasone 96 mg vs 16 mg per day for malignant spinal-cord compression treated by radiotherapy: TROG 01.05 Superdex study

Abstract

Aim: To test the viability of a full-scale randomised comparison of two steroid doses given with radiotherapy for malignant spinal-cord compression (MSCC), to test Internet randomisation and to compare different functional outcome measures.

Materials and methods: A log of screened patients at eight recruiting centres was maintained. Patients were randomised via the Superdex website to either 96 mg or 16 mg daily of dexamethasone. Radiotherapy treatment was 30 Gy in 10 fractions. Outcomes assessed used ambulation, Barthel Index ambulation, Functional Independence Measure (FIM) ambulation and Functional Improvement Score (FIS) at 1 month.

Results: One hundred and thirty-one patients were screened. Ninety-three (71%) were ineligible, 65% of these were because duration of prior steroid use was greater than 12 h, failure to meet strict definition of magnetic resonance imaging, defined MSCC, multi-level disease or previous spinal-cord compression treatment. Twenty of the 38 eligible patients were randomised, including seven outside standard office hours. There was a high rate of serious adverse events (n = 9), but only one was considered likely to be related to study medication. At baseline, 75% were ambulant, 70% had FIM ambulation scores greater than 5 and 50% had Barthel Index ambulation scores greater than 2. At day 28, including all randomised patients (by scoring four dead patients as non-ambulant), ambulation scores by the various definitions were 60%, 45% and 40%, respectively. For the 16 patients evaluable at day 28, the mean FIS was -1.4. Median survival was 69 days and 1-year survival 13%.

Conclusion: Web randomisation was successful; however, the high ineligibility rate precludes a full-scale dexamethasone dose trial in Australia. Choice of measure of ambulation has potentially significant effects on outcomes and implications for the design of any future MSCC trials. Referral delays are of concern.