Recurrent nodal metastases in the posterior triangle: implications for treatment of the atypical tumour.

We studied the incidence of recurrent nodal metastases in level V (posterior triangle) in patients who had previously had a staging or therapeutic dissection of the neck, with or without postoperative radiotherapy. Of 160 patients studied (177 neck dissections), 41 (26%) developed recurrent metastases in the neck. Four patients (3%) developed ipsilateral recurrent disease in level V. In these four patients, level III or IV lymph nodes were shown histologically to have extracapsular spread at the time of the original dissection. All four metastases were located at or just beyond the anatomical boundaries of the posterior triangle. None of the metastases at level V were from oral or oropharyngeal primary tumours.

A short fractionation radiotherapy treatment for poor prognosis patients with high grade glioma.

Thirty-two patients prospectively identified as having poor prognosis high grade glioma, with a MRC prognostic score >25, were treated with a short palliative course of radiotherapy. A total dose of 36 Gy in 12 fractions was given to the tumour, including oedema and a 2 cm margin, using parallel pair fields prescribed to the midplane with MV photons. Twenty-eight patients completed treatment as planned, while four failed to complete treatment because of clinical deterioration or death. The median survival for the whole group was 16 weeks, with seven patients surviving for more than 6 months. Approximately two-thirds of the surviving patients remained at home after the completion of treatment. A matched case-control comparison with data from patients in previous MRC studies who had received a 6-week course of treatment shows that, for this group of patients, survival is similar (hazard ratio 1.0; 95% confidence interval (CI) 0.57-1.74). The 95% CI for the difference in median survival time excludes a reduction of more than 7 weeks with the 36 Gy course. This shortened radiotherapy regimen may therefore be satisfactory for most poor prognosis patients. However, patients with performance status 3 gained little benefit from treatment, and it is suggested that this group should have a trial period of assessment at home prior to a decision on treatment.

Phase I study of etoposide with SDZ PSC 833 as a modulator of multidrug resistance in patients with cancer.

PURPOSE: To determine the maximum-tolerated dose (MTD) and toxicity of PSC 833 infusion administered with etoposide for 5 days in patients with cancer, and to determine the effect of PSC 833 on etoposide pharmacokinetics. PATIENTS AND METHODS: Thirty-five patients were entered onto the study, one of whom was ineligible. Etoposide was delivered from day 1 as a 2-hour infusion over 5 consecutive days at a dose of 75 to 100 mg/m2/d. PSC 833 was administered from day 2 as a 2-hour loading dose and as a 5-day continuous infusion. Doses were escalated from 1 to 2 mg/kg (loading dose) and 1 to 15 mg/kg/d (continuous infusion). RESULTS: Thirty-four patients were treated with 53 cycles of PSC 833 and etoposide. Steady-state blood PSC 833 levels more than 1,000 ng/mL were achieved in all patients treated at PSC 833 doses > or = 6.6 mg/kg/d by continuous infusion. Myelosuppression was the most common toxicity. The major dose-related toxicity of PSC 833 was reversible hyperbilirubinemia, which occurred in 83% of cycles. The dose-limiting toxicity of PSC 833 was severe ataxia, which occurred in two of nine patients treated at 12 mg/kg/d and in both of the single patients treated at 13.5 and 15 mg/kg/d. PSC 833 concentrations more than 2,000 ng/mL resulted in an increase in etoposide area under the curve (AUC) of 89%, a decrease in etoposide clearance (Cl) of 45%, a decrease in volume of steady-state distribution (Vss) of 41%, and an insignificant increase in alpha half-life (t 1/2 alpha) and significant increase of beta half-life (t 1/2 beta) of 19% and 77%, respectively. CONCLUSION: PSC 833 can be administered in combination with etoposide with acceptable toxicity. The recommended continuous infusion dose of PSC 833 for this schedule is 10 mg/kg/d over 5 days. PSC 833 results in an increase in etoposide exposure and etoposide doses should be reduced in patients receiving PSC 833.