Action to Cure Kidney Cancer

Dr. SrikalaSridhar , from the Princess Margaret Hospital in Toronto, presented the results of a multi-center, open-label phase II trial of the drug cediranib. Cediranib is a VEGFR tyrosine kinase inhibitor, like sunitinib (Sutent) and sorafenib (Nexavar), and works by preventing tumors from growing blood vessels, specifically inhibiting VEGFR1, VEGFR2, and VEGFR3.

This Phase II trial, which enrolled patients who had no prior systemic therapy, achieved a disease control rate, by RECIST-defined response standards, of 86% (the total of partial responses and stable disease).

Methods

Forty-three patients were enrolled in the cediranib trial, with a median age of 62. They were each administered 45 mg of the drug daily until disease progression. Dose reductions were required in 34 patients.

Adverse Events

The adverse events observed in patients on cediranib were not unlike those observed in trials of other angiogenesis-inhibitors. The most common are listed below:

Voice alteration may stick out, though it is a common side effect stemming from stimulation of the trachea and vocal cord. Dyspnea[1] occurs in patients for the same reason. The researchers also compiled a list of adverse events ordered by severity. The most frequent adverse events above grade 3 are listed below:

The researchers did not mention whether or not the adverse events recorded were easily handled with additional medication, though as the side-effect profile for cediranib mirrors those of other angiogenesis inhibitors, one would assume that the safety profile does too.

Results

The response data for the 37 patients evaluated is as follows:

Though there were no complete responses recorded, the overall response rate for cediranib was 35%. The tumor control rate (the number of patients in whom the disease was at least stabilized while treated with cediranib) was 86%. Of the 19 patients with stable disease, 6 are reported to have shown tumor shrinkage just below RECIST standards (>20% unidimensional decrease), excluding them from a progressive response classification. The 6 patients deemed unevaluable either withdrew consent or were felled by intercurrent illness.

The median length of Progression-Free Survival was 9.4 months, and at the 6-month mark of the trial 63% of patients were without disease progression. Of the 43 original patients enrolled, 13 still remained on cediranib at the date of the presentation.

Conclusions

The results of the most recent cediranib phase II trial are very encouraging and more than warrant further research. However, the field of targeted therapies for kidney cancer is becoming crowded, and AstraZeneca has not made a decision as to future development plans for cediranib. As an AstraZeneca rep told ACKC, they are "still evaluating the data and considering our next steps as it relates to kidney cancer".

[1] Difficulty in breathing.