Aristu JJ et al. – Maximal tolerated dose for preoperative intensity-modulated radiotherapy combined with capecitabine and oxaliplatin is 47.5 Gy; high rates of pathologic response of grade 3+ and 4 must be confirmed with new pts in the phase II study Methods
Study to identify the maximal tolerated dose of preoperative intensity-modulated radiotherapy combined with capecitabine and oxaliplatin and to evaluate efficacy in pts with rectal T3-T4 and/or N0-N+ rectal cancer
Administration of capecitabine 825 mg/m2 twice daily Monday-Friday and oxaliplatin 60 mg/m2 IV on Days 1, 8, and 15, concurrent with intensity-modulated radiotherapy
Radiation dose increased in 5-Gy steps in cohorts of 3 pts from 37.5 Gy in 15 fractions (dose level [DL] 1)
DL2 and DL3 designed to reach 42.5 Gy in 17 fractions and 47.5 Gy in 19 fractions, respectively
Results
No dose-limiting toxicity at DL1 or DL2
Of the 3 pts treated at DL3, 1 had grade 3 diarrhea considered a dose-limiting toxicity; 3 additional pts were added
No new dose-limiting toxicities for the 6 pts treated at DL3; DL3 identified as recommended dose
Treatment at 47.5 Gy for 8 additional pts
Adverse events: most frequent (40%), grade 2 proctitis; 2 pts (10%) had grade 3 diarrhea
Surgery for all pts; R0 resection for 17 pts (85%)
Histologic response: grade 4 for 4 pts (20%); grade 3+ for 11 (55%); grade 3 for 2 (15%); grade 2 for 2 (10%)
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