European Journal of Cancer: Highlights of Issue 37:07

Non-invasive techniques to measure angiogenesis.

Angiogenesis, the formation of new blood vessels, is often a requirement if tumour cells are to proliferate and thus the development of angiogenic inhibitors as candidate anti-cancer drugs is of paramount importance. In order to measure the effects of these drugs, new techniques capable of measuring both angiogenic and anti-angiogenic activity in vivo are being developed. Ideally, these assays should distinguish between pre-existing host vessels and induced angiogenesis, not damage tissue, be non- invasive and permit long-term monitoring. In this issue, Kragh and colleagues report on two techniques that fulfil most of these criteria, laser Doppler flowmetry and near-infrared spectroscopy. By using these two methods to measure local blood perfusion in superficial tissues and haemoglobin concentrations, respectively, the authors were able to demonstrate significant differences in angiogenic activity between basic fibroblast growth factor (bFGF)-treated and placebo-treated nude mice as well as study the effects in this model of anti-angiogenic compounds such as TNP-470.

Liposomal doxorubicin: in the treatment of advanced soft tissue sarcomas (STS)

Doxorubicin is a key agent in the treatment of soft tissue sarcomas (STS). However, it's use is limited by side-effects such as bone marrow suppression and cumulative cardiotoxicity. New preparations of the drug have therefore been developed with the aim of reducing such dose-limiting effects. One such preparation is a liposomal form of the drug (DOXIL â/CAELYX â) which is less readily eliminated from the body and thus has a longer half-life. Phase I trials have shown the preparation reduces alopecia, myelosuppression and cardiotoxicity compared with the parent compound. In this issue, Judson and colleagues compare CAELYX â with standard doxorubicin in a randomised Phase II setting. They randomised 94 patients with advanced STS to receive 50mg/m2 of CAELYX â as a 1h intravenous (i.v.) infusion every 4 weeks or a 75mg/m2 i.v. bolus of doxorubicin every 3 weeks. The two drugs showed equivalent activities, but the liposomal preparation was generally less toxic (with the exception of skin toxicity). The authors concluded that the preparation 'should be considered for further investigation in combination with other agents such as ifosfamide'.

Liposomal doxorubicin: in the treatment of advanced Kaposi's sarcoma

Liposomal doxorubicin has also found a use in the treatment of AIDS-associated Kaposi's sarcoma patients. As there is presently no cure for these patients, there is a need for a long-term maintenance therapy. These patients are often severely immunocompromised, thus toxic side-effects resulting from long-term chemotherapy can limit any treatment strategies. Hengge and coworkers report in this issue on the use of liposomal doxorubicin in a Phase II trial carried out over 4 years in 52 patients with advanced KS and concluded that the drug was safe and effective for use as long-term chemotherapy in patients with advanced KS. The patients in this study were treated in the pre-HAART era and so it is debatable how relevant the use of liposomal doxorubicin would be in the treatment of today's patient. However, it is clear from the above two examples that the design and development of new drug preparations derived from existing effective parent compounds with the aim of reducing toxicity is a sensible strategy that should hopefully bear fruit in the future.

ON A RELATED THEME, PLEASE NOTE THE EUROPEAN JOURNAL OF CANCER WILL BE PUBLISHING A SPECIAL ISSUE ON 'AIDS AND CANCER' LATER THIS YEAR.

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