Control of pelvic cancer with hyperthermic isolation-perfusion

Eight patients with refractory pelvic cancer were treated with a technique of hyperthermic pelvic isolation-perfusion (rectosigmoid colon 7, bladder 1). The procedure was successful in achieving regional hyperthermia in all patients. All five patients experiencing severe pelvic pain prior to surgery had resolution of pain, although in one patient this relief was transient. Five patients had additional intraabdominal procedures at the time of laparotomy to control unsuspected foci of recurrent cancer. There were no operative deaths. Five complications occurred in four patients although only one was considered life threatening (fracture of aorta at the time of cross-clamping). Sloughing of necrotic tumor occurred between 1 and 2 weeks postperfusion and at times was dramatic. The efficacy of this technique is impressive and it is suggested that it be utilized earlier in the course of disease in patients with uncontrolled pelvic cancer.     

Allopurinol dosage selection: relationships between dose and plasma oxipurinol and urate concentrations and urinary urate excretion.

1. Allopurinol usage in 50 patients of a city teaching hospital was surveyed. 2. The plasma concentrations of oxipurinol and uric acid and the urinary production of uric acid were examined. 3. The daily doses of allopurinol ranged from 50 to 1200 mg but 83% of patients were taking 300 mg daily. 4. A wide range of plasma oxipurinol concentrations was observed from 2.8 to 55.8 mg l-1 with a mean +/- s.d. of 15.2 +/- 11.7 mg l-1. 5. The population studied included a high proportion of patients with renal impairment and creatinine clearance was a significant determinant of oxipurinol concentrations (P less than 0.005). 6. There was no significant correlation between plasma urate and plasma oxipurinol concentrations and only a few plasma urates were above the upper limit of the reference range of the laboratory. 7. It was apparent that many patients were taking unnecessarily high daily doses of allopurinol and that renal status was not always considered when deciding dosage regimens of allopurinol.     

Case 30: hypereosinophilia

A young man presented with systemic symptoms and marked eosinophilia. Subsequently cyclical weight gain and edema contributed to a diagnosis.     

Response rate or time to progression as predictors of survival in trials of metastatic colorectal cancer or non-small-cell lung cancer: a meta-analysis

BACKGROUND: The duration and cost of cancer clinical trials could be reduced if a surrogate endpoint were used in place of survival. We did a meta-analysis to assess the extent to which two surrogates, tumour response and time to progression, are predictive of mortality in metastatic colorectal cancer and non-small-cell lung cancer. METHODS: Summary data (median time to progression, proportion of patients responding to treatment, and median overall survival) from randomised trials of first-line treatment in colorectal cancer (146 trials) and lung cancer (191 trials) were identified. Data were extracted and analysed by linear regression. We used prediction bands for trials with 250, 500, and 750 patients to identify the surrogate threshold effect that would predict a significant difference in survival. FINDINGS: Response to treatment and time to progression correlated with improvement in survival for both lung cancer (p<0.0001 and p=0.0003, respectively) and colorectal cancer (p<0.0001 for both). To predict a significant survival gain in colorectal cancer trials, an improvement of 20% in the number of patients responding to treatment was required in trials with 750 patients, increasing to 26% in trials with 500 patients and 38% in trials with 250 patients. In lung cancer trials, the same prediction required differences in response of 18% for 750 patients, 21% for 500 patients, and 30% for 250 patients. For time to progression for both cancer types, the incremental gain needed to predict a survival improvement was a median of 1.8 months for trials with 750 patients, 2.2 months for 500 patients, and 3.3 months for 250 patients. INTERPRETATION: Irrespective of trial size, large differences in tumour response rate are needed to predict a significant survival benefit. If surrogates are chosen as the primary endpoint in a clinical trial, time to progression is the preferred measure because more modest and achievable differences are needed for a significant survival benefit. Trials in metastatic lung cancer and colorectal cancer should measure survival as their primary outcome unless the surrogate outcome difference is anticipated to exceed the threshold effect size.     

Where next for gefitinib in patients with lung cancer?

Gefitinib belongs to the small-molecule class of epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors. It was given conditional approval by the US Food and Drug Administration (FDA) in 2003 for treatment of advanced, chemorefractory non-small-cell lung cancer (NSCLC), but was relabelled for restricted use for patients that were already receiving and benefiting from it after the negative result of the phase III Iressa Survival Evaluation in Advanced Lung Cancer (ISEL) trial. By contrast, erlotinib, another EGFR tyrosine-kinase inhibitor, showed an overall survival benefit compared with placebo and best supportive care in the National Cancer Institute of Canada's BR21 trial, and now has full FDA approval for treatment of patients with NSCLC who have progressed after treatment with chemotherapy. Although the ISEL trial result was negative overall, preplanned subgroup analyses showed a significant overall survival benefit for gefitinib treatment in never-smokers and in patients of Asian origin. Here, we review the clinical experience with gefitinib and, in light of the licensing of erlotinib, address the lessons learned, the ongoing trials, and whether scope remains for clinical development of gefitinib in selected patients.     

Nematode symbiont for Photorhabdus asymbiotica

Photorhabdus asymbiotica is an emerging bacterial pathogen that causes locally invasive soft tissue and disseminated bacteremic infections in the United States and Australia. Although the source of infection was previously unknown, we report that the bacterium is found in a symbiotic association with an insect-pathogenic soil nematode of the genus Heterorhabditis.