An assessment of the relative importance of the components of CYVADIC in the treatment of soft-tissue sarcomas using regression meta-analysis

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Abstract
The CYVADIC combination has enjoyed popular medical support for over a decade in the treatment of soft-tissue sarcomas, and there is much documented evidence in the literature of the relative success of this and related regimes. A multivariate regression meta-analysis has been undertaken of the collective experience of this group of regimens, to assess statistically the relative importance of each component of CYVADIC using the intensities of the four components to predict objective tumour response. This analysis demonstrates that the tumour response to a specific regimen may be reasonably predicted from an expression that is highly sensitive to the dacarbazine dose intensity, with a significant additional contribution being introduced by the level of vincristine administered. There is convincing statistical evidence that, when administered as part of a CYVADIC chemotherapeutic regimen, the presence of doxorubicin (with an intensity of about 0-8) will produce a significant optimal effect on tumour responses. In such situations there is no detected significant benefit from increasing the dose of doxorubicin beyond this critical level of intensity. These findings suggest that it is dacarbazine and not, as is customarily argued, doxorubicin that is the most sensitive component in the CYVADIC treatment of soft-tissue sarcomas. The veracity of this conclusion should be tested by prospective studies designed specifically to escalate the intensity of dacarbazine treatment, whilst holding the level of doxorubicin at below standard intensity.