October 1 Clinical Cancer Research Highlights

Radiotherapy followed by total mesorectal excision (TME) surgery has been shown to significantly reduce local recurrence rates in rectal cancer patients. Radiotherapy, however, is associated with considerable morbidity. de Heer and colleagues evaluated the use of biochemical detection of enzymatic caspase-3 activity as preoperative marker for apoptosis to preselect patients unlikely to develop a local recurrence in order to spare these patients from overtreatment and the negative side effects of radiotherapy. The authors concluded that detection of tumor apoptosis levels by measuring caspase-3 activity, for which a preoperative biopsy can be used, accurately predicted local recurrence in rectal cancer patients.

Flavopiridol is a cyclin-dependent kinase inhibitor that enhances docetaxel-induced apoptosis in a sequence-specific manner. In vivo, docetaxel must precede flavopiridol by at least 4 hours in order to induce this effect. Fornier and coauthors conducted a Phase I trial of weekly, sequential docetaxel followed 4 hours later by flavopiridol in patients with advanced solid tumors. This combination regimen was found to be effective and safe at all flavopiridol dose levels. Pharmacokinetic data indicate that concentrations of flavopiridol can be achieved that enhance the effects of docetaxel both in vitro and in vivo. The clinical activity was encouraging, even in patients who received a prior taxane and in patients with gemcitabine-refractory metastatic pancreatic cancer.

The Milan criteria was made based on the poor outcome of advanced hepatocellular carcinoma (HCC) patients receiving live transplantation (LT) and the limited source of donor organs. To explore the possibility of expanding Milan criteria, Li and colleagues evaluated the effect of ADV-TK therapy on 45 HCC patients with tumors > 5 cm. HCC patients without vascular invasion receiving LT plus ADV-TK displayed obvious improved outcome compared with the patients receiving LT only. The current criteria for LT based on tumor size may be expanded if accompanied by ADV-TK therapy.

Ali et al.

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