Neoadjuvant radiotherapy (RT) combined with capecitabine (Cape) and sorafenib (Sor) in patients with locally advanced, K-ras-mutated rectal cancer (LARC): A phase I/II trial (SAKK 41/08).

3595 Background: 40% of patients (pts) with LARC present with K-ras mutation. Sor is an inhibitor of ras/raf and of VEGFR. Furthermore Sor has radiosensitizing effects. These facts build a strong rationale to use Sor in combination with preoperative RT and Cape in pts with K-ras mutant tumors. Methods: Pts with K-ras mutated mrT3-4 and / or mrN+, M0 disease were recruited in cohorts of 7 pts per dose level (DL). Dose limiting toxicity (DLT) was defined as any G3 or higher non hematological toxicity (tox) or haematological tox during ≥ 7 days, which are possibly, probably or definitely related to trial treatment occurring during and up to 4 weeks after last administration. If ≤ 2 out of 7 pts experienced a DLT, then the next cohort was treated at a higher dose level. If > 2 out of 7 pts suffered from a DLT, this DL would be considered too toxic and a dose level below would be tested in the next cohort. The highest dose level with ≤ 2 out of 7 pts experienced a DLT would be recommended for the phase II part...