The use of pharmacokinetic and pharmacodynamic end points to determine the dose of AQ4N, a novel hypoxic cell cytotoxin, given with fractionated radiotherapy in a phase I study.

BACKGROUND: AQ4N (1,4-bis[[2-(dimethylamino)ethyl] amino]-5,8-dihydroxyanthracene-9, 10-dione bis-N-oxide dihydrochloride) is a prodrug which is selectively activated within hypoxic tissues to AQ4, a topoisomerase II inhibitor and DNA intercalator. PATIENTS AND METHODS: In the phase I study, 22 patients with oesophageal carcinoma received an i.v. infusion of AQ4N (22.5-447 mg/m(2)) followed, 2 weeks later, by further infusion and radiotherapy. Pharmacokinetics and lymphocyte AQ4N and AQ4 levels were measured after the first dose. At 447 mg/m(2), biopsies of tumour and normal tissue were taken after AQ4N administration. RESULTS: Drug-related adverse events were blue discolouration of skin and urine, grade 2-3 lymphopenia, grade 1-3 fatigue, grade 1-2 anaemia, leucopenia and nausea. There were no drug-related serious adverse events (SAEs). Three patients had reductions in tumour volume >50%, nine had stable disease. Pharmacokinetics indicated predictable clearance. Plasma area under the curve (AUC) at 447 mg/m(2) exceeded AQ4N concentrations in mice at therapeutic doses and tumour biopsies contained concentrations of AQ4 greater than those in normal tissue. Tumour concentrations of AQ4 exceeded in vitro IC(50) values for most cell lines investigated. CONCLUSIONS: No dose-limiting toxic effects were observed and a maximum tolerated dose was not established. Tumour AQ4 concentrations and plasma AUC at 447 mg/m(2) exceeded active levels in preclinical models. This dose was chosen for future studies with radiotherapy.

Latest trends in cancer incidence among UK South Asians in Leicester.

Using cancer registry data, we show that although South Asians have lower rates of cancer than the rest of the population, this is changing with age and time. Younger South Asians, particularly children, are at increased risk. While generally cancer rates have fallen over the last decade, they are increasing among South Asians.

Computerizing the cancer centre.

This article describes a PC-based computer network that caters for the clinical information needs of a cancer centre, crossing specialty boundaries and involving all members of the multidisciplinary team. Data are captured at all stages of patients' progress, from diagnosis through to treatment and follow-up. Office automation is integral to the system, which produces work-load and process audit information as well as clinical outcomes. Data are entered prospectively at the point of care by health care professionals, ensuring a high degree of clinical confidence. It incorporates internationally recognized datasets and its modular structure facilitates implementation and development.

Laser therapy combined with brachytherapy for the palliation of malignant dysphagia.

BACKGROUND/AIM OF STUDY: Laser therapy is effective in relieving malignant dysphagia, but repeated treatments at 4 to 6 week intervals are usually required. This prospective randomised trial is designed to determine if addition of brachytherapy offers any advantages over laser therapy alone. METHODS: Patients with inoperable carcinoma of the oesophagus were randomised to receive either endoscopic Nd:YAG laser therapy alone, or laser followed by brachytherapy. Patients who developed worsening dysphagia during follow-up were offered further treatment as appropriate. RESULTS: Fourteen patients were randomised to receive laser only, and 12 to receive laser followed by brachytherapy. Of these 12, one was lost to follow-up and four did not receive brachytherapy because they were unfit, had extension into the cardia or had mainly extrinsic compression. These 4 are included on an 'intention-to-treat' basis. The mean therapeutic interval for the brachytherapy group was significantly longer, 83 days compared to 36 days for the laser group (p = 0.026). There were no differences in the degree of dysphagia relief, number of endoscopic procedures or survival times. CONCLUSION: The preliminary results of this trial suggest that brachytherapy in addition to laser therapy prolongs the first therapeutic interval. However, no long-term advantages have been shown.

Provision of cancer treatment services: the role of a district general hospital department of clinical oncology.

Recent reports from the Royal College of Radiologists have highlighted the debate surrounding the provision of cancer services. This review describes the work of a district hospital based department of clinical oncology, emphasizing the access to and the outcome and scope of treatment. The findings indicate that district general hospital based cancer centres can provide a comprehensive, accessible, high quality consultant based service.

Natural history and prognosis of prostate carcinoma in adolescents and men under 35 years of age.

Prostate cancer is extremely rare in men under 35 years of age. The tumour is invariably poorly differentiated and aggressive, with rapidly growing bulky soft tissue metastases and negative tumour markers. Bone metastases develop late and are usually osteolytic. The disease responds poorly to radiation or hormonal therapy and is too advanced at presentation for radical surgery. Chemotherapy appears to be of some benefit, though in the majority of cases death occurs within a year. We describe a 31-year-old man with carcinoma of the prostate. A review of the literature is presented. This is the first patient in whom the epithelial origin of the prostate cancer was confirmed by immunoperoxidase staining with prostatic specific antigen. Plasma prostatic specific antigen was normal despite a large tumour burden and widespread metastases. He did not respond to conventional treatment. The phenotypic expression and biological behaviour of these tumours are distinct from those occurring in men beyond the fourth decade.

Primary Hodgkin's disease of bone.

Primary Hodgkin's disease of bone is rare. Diagnosis is often delayed and may be mistaken for eosinophilic granuloma. We report such a case where Hodgkin's disease presented as a primary osteolytic bone lesion.

Results of treatment of primary breast carcinoma by radical radiotherapy with artificial pneumothorax.

One hundred and forty-three women with primary breast carcinoma were treated by radical radiotherapy associated with artificial pneumothorax to include the breast and lymphatics en bloc with large opposed fields. Surgery was restricted to local excision or drill biopsy. Most patients received a tumour dose of 5200-5600 cGy in 19-22 fractions over 4 weeks and were followed up for at least 5 years. Local control was achieved in 87% of T1, 52% of T2, 27% of T3 and 23% of T4 tumours. For T2 tumours local control was greater following excision biopsy (75%) than when surgery was more limited (21%). Acute morbidity was mostly minor and self-limiting. The commonest permanent late complication was restriction of shoulder movement in 20 patients. This method although safe and feasible does not offer significant advantages over conventional techniques.

Juvenile nasopharyngeal angiofibroma treated by radiotherapy.

A case of juvenile nasopharyngeal angiofibroma is reported and its response to radiotherapy demonstrated. The literature is reviewed and the use of radiotherapy for advanced tumours is advised.

Megestrol acetate in the treatment of advanced post-menopausal breast cancer.

The effect of megestrol acetate 160 mg daily was studied in 49 previously treated post-menopausal patients with advanced carcinoma of the breast. An overall response of 31% was obtained with 1 complete and 14 partial remissions, chiefly in soft tissue and bone. The median duration of response was in excess of 10 months. Toxicity was minimal and the only notable side effect was mild weight gain without fluid retention. Megestrol acetate is safe and well tolerated, with useful activity in the palliation of advanced breast cancer.