Newsdesk
Doubts expressed about potential new anticancer drug Scientists warn this month that more work must be done before tumour necrosis factor-related apoptosisinducing ligand (TRAIL), a potential anti- cancer agent, enters clinical trials. “In our in vitro experiments”, says Stephen Strom (University of Pittsburgh, PA, USA), “apoptosis occurred within 10 hours in more than 60% of primary human hepatocytes exposed to TRAIL. This indicates that it could cause considerable hepatotoxicity in people. The studies done so far by Genentech and Immunex, joint developers of TRAIL, have been thorough”, adds Strom, “but more use should be made of primary human cells in the preclinical evaluation of this and other new therapeutic agents”. Interest in TRAIL as an anti-cancer agent has been keen because, unlike tumour necrosis factor, it induces tumour regression in mice and non-human primates without severe side-effects. However, Strom’s team, who were investigating whether TRAIL was involved in liver damage in hepatitis, found that it killed more than 60% of a primary culture of hepatitis-C-infected hepatocytes within hours, and were surprised to find “similar results with uninfected liver cells, even though TRAIL does not kill liver cells from other species and there has been no liver toxicity in preclinical trials in animals” (Nat Med 2000; 6: 564 – 67). Ex-Immunex researcher Henning Walczak (German Cancer Research Centre, Heidelberg) agrees that Strom’s results “sound a cautionary note”, but because the sensitivity of the human hepatocytes to TRAIL might be an in vitro artefact, “these results should not lead to a total halt on the start of trials”. “We take Dr Strom’s data very seriously”, adds Immunex’s Chief Technology Officer Doug Williams, “and are collaborating with him to look into his results more fully. However, at present, we believe clinical trials will still start late this year or early next”. Jane Bradbury THE LANCET Oncology May 2000
Report highlights lung cancer in Brazilian women Lung cancer is now the second biggest neoplastic cause of death among women in Brazil, exceeded only by breast cancer. According to a recent report by Brazil’s National Cancer Institute, and based on data from 1980 to 1997, lung cancer has overtaken cervical cancer in the number of registered deaths. Jacob Kligerman, General Director of the Institute, says this is due to the increasing numbers of women smokers since the 1960s. A projected 4232 women will die of lung cancer in Brazil this year (see Table 1). Other research results had already shown an increase in smoking among female teenagers. In 1987, boys smoked more than girls, but 10 years later there was clear evidence that smoking rates were similar in both sexes. The report estimates that, today, there are 38 million smokers in Brazil.
The risk of dying of lung cancer is 22fold higher among this group than for non-smokers, with a 5-year survival rate after diagnosis of 13%. The annual report (www.inca. org.br), predicts that, overall, there will be 284 205 new cases of cancer in Brazil in 2000, and 113 959 deaths. Cancer is the third highest cause of death (11.84%) and, compared with other diseases, ranks second (27.63%), after cardiovascular disease. Skin cancer will account for most new cases this year (42 305), followed by breast (28 340), lung, stomach, and cervical cancer. Lung cancer will cause 14 522 deaths, followed by gastric, breast, and prostate cancer. One of the reasons for the rising incidence of cancer is the ageing population, which extends exposure to risk factors. Claudio Csillag
Table 1. Cancer deaths by type Site
Men
%
Women
%
Skin (non melanoma)
402
0.65
267
0.51
Total 669
Breast
-
-
8245
15.72
8245
Lung
10 290
16.73
4232
8.07
14 522
Stomach
7090
11.52
3610
6.88
10 700
Cervical
-
-
3606
6.87
3606
Prostate
6850
11.13
-
-
6850
Colon and rectal
3162
5.14
3563
6.83
6725
Oesophagus
3968
6.45
1194
2.27
5162
Leukaemia
2311
3.76
1880
3.58
4191
Mouth
2471
4.02
606
1.15
3077
Other
24 978
40.60
25 234
48.12
50 212
TOTAL
61 522
100.00
52 437
100.00
113 959
Postcard system helps follow up lost patients Cancer hospitals generally conduct follow-up studies after the completion of primary treatment, to assess the disease status of the patient. In India, the survival data available from various cancer registries show a high proportion lost to follow up (LFU). Methods used to minimise LFU patients in developed countries are not practicable in India, but researchers at the Regional Cancer Centre (RCC), (Trivandrum Kerala, India) have used a simple postal enquiry system – using pre-paid postcards – to obtain followup information on 352 ovarian cancer patients registered at RCC. This improved the overall follow-up rate
from 33% to 69%, and information on disease status was obtained for 53% of LFU patients (Indian Journal of Cancer 1999; 36: 91 – 98). “Cancer survival data provide a summary index of the efficacy of a particular treatment, identify prognostic factors and help us to understand the biological behaviour of tumours. This is particularly important in developing countries, where treatment resources are not easily available and optimisation of treatment regimens is of paramount importance”, says Madhavan Krishnan Nair, RCC Director, and a co-author of the paper. Dinesh Sharma 7