Efficacy and pharmacokinetics of a new controlled-release morphine sulfate 200-mg tablet.

Nineteen of 25 patients (14 female) with advanced malignant disease completed a randomized controlled trial of a new high-dose (200 mg) tablet formulation of controlled-release morphine. Compared with the currently available 100-mg tablets there were no differences in pain severity or adverse effects with the new formulation. In four patients, full 12-hr plasma morphine concentration profiles at steady state were obtained and showed no significant differences between the same dose provided as 100-mg and 200-mg tablets in Cmax, tmax, or other pharmacokinetic indices.

Small cell carcinoma of the cervix.

Small cell carcinoma of the cervix represents an uncommon variant of cervical cancer with a particularly poor prognosis. Traditionally, the diagnosis was established from routine histopathological sections, but there has been a trend to refer to this tumour as neuroendocrine carcinoma, with a requirement to demonstrate cytoplasmic granules. Five patients are described, who share the clinical features of young age of onset, early metastasis in the presence of apparently low stage disease, early failure of appropriate local treatment, and extreme chemosensitivity (features that are quite distinct from those seen in squamous cell cancer of the cervix). Light microscopy suggested a diagnosis of small cell cancer in all five tumours, but not all showed evidence of neuroendocrine differentiation. It is proposed that the present criteria for the diagnosis of cervical small cell carcinoma are too strict. The diagnosis should rely on the light microscopy of haemotoxylin and eosin sections and the distinctive clinical behaviour. The absence of neuroendocrine differentiation should not exclude the diagnosis, it does not appear to influence the clinical behaviour. The appropriate management of small cell carcinoma of the cervix is systemic, with chemotherapy as the first line of treatment. Surgery and radiotherapy may improve control of local disease but are unlikely significantly to influence the overall prognosis.

Radiation myelopathy: estimates of risk in 1048 patients in three randomized trials of palliative radiotherapy for non-small cell lung cancer. The Medical Research Council Lung Cancer Working Party.

Radiation myelopathy (RM) is an uncommon but serious late effect of thoracic radiotherapy (RT), which oncologists try to avoid by careful planning and dose selection. Five patients with RM are described from among 1048 with inoperable non-small cell lung cancer treated with palliative RT in three randomized trials conducted by the Medical Research Council Lung Cancer Working Party. Seven RT regimens were used in these trials: 10 Gy in a single fraction on one day (10/1/1) (114 patients), 17/2/8 (524 patients), 27/6/11 (47 patients), 30/6/11 (36 patients), 30/10/12 (88 patients), 36/12/16 (86 patients) and 39/13/17 (153 patients). Of the five instances of RM, three occurred in the 524 patients treated with 17 Gy in two fractions, and two in the 153 treated with 39 Gy in 13 fractions. The estimated cumulative risks of RM by 2 years were 2.2% for the 17 Gy group, 2.5% for the 39 Gy group, and 0% for the remainder, but the annual risks had wide 95% confidence intervals, indicating that the distribution of episodes among the seven regimens could have been random. Nevertheless, calculation of cord doses in terms of the total doses that would have an equivalent biological effect if given in 2 Gy fractions (LQED2 values) from our data for different values of the ratio of the linear quadratic parameters of the cell survival curve (alpha/beta), suggest that the best estimate of alpha/beta is less than 3 Gy, and possibly close to 2 Gy. This emphasizes the sensitivity of human spinal cord to changes in fraction size. We recommend that, when the computed LQED2 for a schedule of treatment that includes the thoracic spinal cord (assuming alpha/beta = 2 for cord) exceeds 48 Gy, oncologists should consider reducing the dose to the cord.

Adenocarcinoma of the ethmoid sinuses in High Wycombe 1986.

Adenocarcinoma of the ethmoid sinus is a rare cancer in this country but relatively common in High Wycombe because of the concentration of furniture factories in this area. The management of five cases occurring recently in the High Wycombe area is described and changes in management since 1960 discussed.