Targeted Therapy in Refractory Thyroid Cancer

Current Achievements and Limitations

Lucia Brilli; Furio Pacini

Disclosures

Future Oncol. 2011;7(5):657-668. 

In This Article

Conclusion

To date, several TKIs appear promising, despite carrying potential limitations. The promising results are represented by an overall improvement of PR rate and disease stabilization compared with conventional chemotherapy or no intervention. Limitations are represented by adverse reactions and resistance. Other issues are represented by a lack of 'individualized' therapy, RECIST criteria and cytoxic versus cytostatic effect.

Although able to target specific oncogene mutations associated with thyroid cancer, effective responses have not yet been associated with a specific oncogenic profile. Indeed, effective responses have been described in both patients with a specific mutation targeted by the drug and those without. This phenomenon has been attributed to a prevalent effect of the drug on the neoangiogenetic pathway rather than on the specific pathway activated by the mutation. Currently, it is not possible to individualize the most effective drug for a given patient based on tumor genotype.

The RECIST assesment, designed to allow objective measurements and reproducible conclusions during the trial, also have some limitations. The chosen target lesions may have no significant response to the drug, while other nontarget lesions may show significant shrinkage. Such cases are not computed as PRs according to RECIST. A second limitation when using RECIST is that patients cannot be treated without predefined demonstration of disease progression. This requirement precludes enrolment of patients with documented metastases at an early stage when, probably, the response to the drug may be greater. A final limitation of RECIST is that, often, a metastatic lesion does not reduce in size during treatment but, upon imaging, it shows evidence of large areas of necrosis. This finding is certainly a beneficial effect of the drug, which is not considered by RECIST.

Target therapy is currently based on cytostatic drugs, meaning that they cannot completely eradicate tumor cells and implying that the drug should be chronically administered (potentially for the rest of the patients life). Should we consider adding cytotoxic drugs to target therapy regimens? An example of this approach is the combination of fosbretabulin with paclitaxel and carboplatin.[114]

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....