European Journal of Cancer: Highlights of Issue 39:06

Targeted therapy unlikely to be active in SCLC

Magic bullet - unlikely to be active in SCLC

STI571 - a new targeted therapy - has been shown to be active in gastrointestinal stromal tumours (GISTs), particularly those with activating mutations in the c-kit exon 11 region. The drug selectively inhibits the activity of various tyrosine kinases including c-KIT. Burger and colleagues have investigated in this issue the mutation status of the c-kit exon 11 in 26 samples taken from SCLC patients. Although c-KIT was expressed in 64% of the tissues examined, no activating mutations were found in any of the samples. The authors suggest that "in analogy to GISTs, their results could imply that SCLC patients would not benefit from treatment with STI571".

Amifostine-potential protector of normal tissues?

Combined therapies that improve selectivity are increasingly being investigated as they may lead to improved therapeutic outcomes. Unfortunately, they are also associated with an increased toxicity in normal tissues. Thus, agents such as amifostine that may be able to act selectively as modulators of toxicity in normal tissues- without affecting the cytotoxic effects of the various agents- are of interest. Amifostine is a pro-drug that is dephosphorylated by membrane-bound alkaline phosphatase (AP) to a free thiol metabolite, WR1065, that is responsible for its protective effects. In this issue Pauwels and colleagues investigated the in vitro effects of gemcitabine and radiation treatment and whether amifostine protected cells from these effects. Gemcitabine increased the radiosensitivity of several cell lines (representing epithelial tumours) in a concentration- and cell line-dependent manner. Amifosine and AP were able to negate the radiosensitive effects of gemcitabine. If this were to occur selectively in normal tissues in vivo then amifostine may be important agent to minimise toxicity and optimise combined therapies.

Factors influencing the outcome of cancer patients referred to ICUs

Maschmeyer and colleagues studied the outcome of 189 consecutive patients who were referred as emergencies to 4 intensive care units (ICUs) in Germany over a 2 year period. There were several reasons for referral including various infections. In their retrospective analysis, no single risk factor predicted death, although their data suggested some subgroups were likely to have a poorer outcome such as those with invasive fungal infections requiring vasopressor support and mechanical ventilation. The authors concluded that a prospective study is needed to confirm the usefulness of this approach. They state that "cancer patients should not be excluded from referral to an ICU in an emergency solely due to their underlying malignant disease or a single unfavourable prognostic factor".

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