European Journal of Cancer: Highlights of Issue 39:13

Synergistic activity of Yondelis (ET-743, trabectidin) and cisplatin in vivo

Yondelis and cisplatin show synergistic activity in vivo with no overlapping toxicities, D' Incalci and colleagues report in this issue. Their rationale behind testing the combination of these two drugs lay in the fact that they have different mechanisms of action with DNA and activate different DNA repair mechanisms. Moreover, the contrasting sensitivities of cell lines with differing repair capabilities to these drugs suggested that they might be advantageously combined, thereby targeting different cell populations within the same tumour. In their study, the two drugs -given in combination- were even active in tumours where single agent treatment had produced little activity. The authors propose that the combination should therefore be tested not only in tumours in which the two drugs given alone are effective, but also in those tumours considered resistant to the single agents. "It seems attractive to test the combination of the two drugs in patients who are relapsing or refractory to first-line chemotherapy", they conclude. In an accompanying editorial, Professor John Smyth suggests that it would be of interest to see these experiments extended to more widely used platinum drugs such as carboplatin.

The treating institution impacts upon the survival of head and neck patients

Patients with advanced squamous cell carcinoma of the head and neck treated at the co-ordinating centre with an alternating chemotherapy and radiation regimen had a better survival than those treated at other centres. This is the conclusion of a study in this issue by Benasso and colleagues using data obtained from 2 multicentre trials. 293 patients were studied (166 treated at the co-ordinating centre) who were given either radiation alone or a combination of alternating chemotherapy and radiation. 3 year overall survival rates were 46% for the patients at the co-ordinating centre compared with 27% at the other centres- a significant difference. There was a more cautious approach in the affiliated centres with regard to the delivery of the combined therapy, despite similar levels of toxicity being observed in both the affiliated and co-ordinating centres. However, no difference in survival was observed between the centres for those treated with radiation alone (23% vs. 21%, respectively). "This finding has implications, both in terms of clinical research and clinical practice", the authors conclude.

Defining ulceration in melanomas

Ulceration in melanomas is considered a major and independent prognostic factor. However, deciding what constitutes ulceration can be difficult to determine, even in experienced hands. In this issue, Spatz and colleagues have defined ulceration as "full-thickness epidermal defect (including absence of stratum corneum and basement membrane), evidence of host response (i.e. fibrin deposition, neutrophils) and thinning, effacement or reactive hyperplasia of the surrounding epidermis". They asked 6 pathologists to examine 100 slides "according to their own experience and interpretation of the literature" (first set) and then examine 100 additional slides- as well as those in the first set which were randomly mixed with the second set- using their definition above. The authors found - using kappa statistics - a superior interobserver reproducibility among the pathologists for the second set of slides. The authors propose that their definition could be incorporated into a standardised pathology worksheet for reporting primary melanomas.

Back . . .