Phase II study of primary temozolomide chemotherapy in patients with WHO grade II gliomas.

BACKGROUND: The aim of this study was to assess the efficacy of temozolomide in patients with World Health Organisation (WHO) grade II gliomas treated with surgery alone using imaging and clinical criteria. PATIENTS AND METHODS: Thirty patients with histologically verified WHO grade II gliomas (17 astrocytoma, 11 oligodendroglioma, two mixed oligoastrocytoma) following surgery 2-104 months (median 23 months) after initial diagnosis received temozolomide 200 mg/m(2)/day for 5 days, on a 28-day cycle, for a maximum of 12 cycles or until tumour progression. Median age was 40 years (range 25-68 years). Median follow-up from entry into the study was 3 years [range 23-47 months (for patients alive)]. Objective response was assessed by 3-monthly magnetic resonance imaging and monthly health-related quality of life (HQoL) and clinical assessment. Tumour size was measured as the high signal intensity area on fluid attenuated inversion recovery sequences. Responses were assessed using change in the product of two perpendicular diameters as complete response (CR), partial response (PR), minimal response (MR), stable disease (SD) and progressive disease (PD). RESULTS: Twenty-nine of 30 patients entered into the study were evaluable for response. Three patients had a PR, 14 MR, 11 SD and one PD. Twenty-four patients received 12 cycles of chemotherapy. Of 29 evaluable patients, three discontinued after four, five and six cycles and two after 10 cycles. Nine patients progressed (three during chemotherapy-one PD and two initial SD-and six after completion of chemotherapy); five had evidence of transformation. The 3-year progression-free survival was 66%. Five patients died; the actuarial 3-year survival was 82%. Ninety-six per cent of patients with impaired HQoL had improvement in at least one HQoL domain. There was improvement in 115 of the 207 domains (56%). Fifteen of 28 patients (54%) with epilepsy had reduction in seizure frequency, of whom six became seizure free. Six patients had transient grade III/IV haematological toxicity (11 episodes; 3.5%). CONCLUSIONS: Temozolomide has single-agent activity in patients with WHO grade II cerebral glioma, with modest improvement in quality of life and improvement in epilepsy control. On present evidence, temozolomide cannot be considered as primary therapy without formal comparison with other treatment modalities.

Hypofractionated radiotherapy for poor prognosis malignant glioma: matched pair survival analysis with MRC controls.

PURPOSE: To assess the survival benefit of palliative hypofractionated radiotherapy in patients with poor prognosis high grade glioma by a matched comparison to conventionally treated controls. METHOD: Ninety-two elderly and/or disabled patients with high grade glioma with poor prognostic features received palliative partial brain radiotherapy to a dose of 30Gy in six fractions over 2 weeks. Patients were matched for WHO histological grade, performance status and age from a cohort of patients treated with conventionally fractionated radiotherapy to a dose of 60Gy in 30 fractions in an Medical Research Council (MRC) BR05 trial. RESULTS: Patients treated with hypofractionated radiotherapy had a median survival of 5 months with a 1-year survival rate of 12% from diagnosis. The median survival of case-matched controls was estimated to be 2.5-4.5 months longer. Following hypofractionated radiotherapy, Barthel score was improved or remained stable in 68% of patients. CONCLUSION: Hypofractionated partial brain radiotherapy is a well-tolerated regimen with palliative benefit. Comparison with matched controls suggests lesser survival benefit than would be obtained with radical radiotherapy. However, this is compensated by lower intensity and duration of irradiation induced side effects. It is postulated that there may not be a significant difference in good quality survival or 'quality adjusted survival' between the two regimens and this requires testing in prospective trials.

Evaluation of a nurse-led telephone clinic in the follow-up of patients with malignant glioma.

The aim of this study was to evaluate nurse-led telephone follow-up (NTF) for patients with high-grade glioma as an alternative to conventional clinic follow-up (CCF) and to assess patient satisfaction with this approach. Patients who were completing primary therapy for high-grade glioma and were suitable for CCF were offered the alternative of nurse-led telephone follow-up. NTF was arranged by the nurse at mutually agreed times. Assessment was by open discussion and a semistructured questionnaire, together with the Barthel Activities of Daily Living Index. Formal medical assessment in the clinic was arranged at 4-month intervals or earlier if indicated. Twenty-two patients were asked to complete a satisfaction questionnaire. Between February 1996 and October 1997, 43 patients with high-grade glioma, one with primitive neuroectodermal tumour and one with oligoastrocytoma agreed to be monitored by NTF. Their median survival from diagnosis was 16 months (95% confidence interval 13-23 months). At the time of analysis, the median time of follow-up by the telephone clinic was 6 months (range 2-21), with symptomatic progressive disease the reason for discontinuation of NTF in all patients. Two-hundred and fifty-four telephone calls were made, of which 234 were routine and 20 non-routine, being initiated by the patients or their carers. NTF was considered as a sufficient replacement for CCF during the stable phase of the disease. There were 41 unscheduled clinic visits, of which 31 were at the time of progression and usually initiated at NTF. The majority of unplanned visits were due to a change in symptoms and would not have been avoided with CCF carried out at the same time intervals. Patient satisfaction was high, with a median satisfaction score of 9, (range 3.6-10 ) on a scale of 0-10. NTF provides an alternative approach to conventional hospital attendance and moves the emphasis away from cancer surveillance to a more patient centred supportive model. It can be carried out without apparent detriment to the patient and is associated with high satisfaction rating.