Preoperative Chemoradiation Therapy With Capecitabine/Oxaliplatin and Cetuximab in Rectal Cancer: Long-Term Results of a Prospective Phase 1/2 Study

Journal Article · Sun Dec 01 04:00:00 EST 2013 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/J.IJROBP.2013.09.011· OSTI ID:22278280

Fokas, Emmanouil ^[1]; Conradi, Lena ^[2]; Weiss, Christian ^[1]; Sprenger, Thilo ^[2]; Middel, Peter ^[3]; Rau, Tillman ^[4]; Dellas, Kathrin ^[5]; Kitz, Julia ^[3]; Rödel, Franz ^[1]; Sauer, Rolf ^[6]; Rüschoff, Josef ^[7]; Beissbarth, Tim ^[8]; Arnold, Dirk ^[9]; Ghadimi, B. Michael ^[2]; Rödel, Claus ^[1]; Liersch, Torsten ^[2]

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1. Department of Radiation Therapy and Oncology, University of Frankfurt (Germany)
2. Department of General Surgery, University Medical Center of Göttingen (Germany)
3. Institute for Pathology, University Medical Center, Göttingen (Germany)
4. Institute of Pathology, University Hospital Erlangen, Erlangen (Germany)
5. Department of Radiotherapy, Lübeck University (Germany)
6. Department of Radiation Oncology, University of Erlangen (Germany)
7. Targos Molecular Pathology, Kassel (Germany)
8. Department of Medical Statistics, University Medical Center of Göttingen (Germany)
9. Tumor Biology Center Freiburg, University of Freiburg (Germany)

Purpose: We have previously shown that the addition of cetuximab to chemoradiation therapy failed to improve complete response rates (pCR) in rectal cancer. Here we report the long-term results of the cetuximab added to preoperative radiation therapy with capecitabine and oxaliplatin (CET-CAPOX-RT) phase 1/2 study that evaluated preoperative chemoradiation with cetuximab, capecitabine, and oxaliplatin in patients with rectal cancer. Methods and Materials: The median follow-up was 63 months (range, 5-73 months). Sixty patients were enrolled; 3 patients were excluded due to protocol violation, and 4 died before surgery. Total mesorectal excision was performed in 53 patients, in 85% (n=45) with curative intention (M0-status). Secondary end points including overall survival (OS) disease-free survival (DFS) and cancer-specific survival (CSS) were calculated. The prognostic value of KRAS mutation status was also assessed. Results: Histopathological examination confirmed ypUICC stages 0 (n=4; pCR), I (n=17), II (n=10), III (n=14), and IV (n=8). For patients who underwent surgery (n=53), OS at 1, 3, and 5 years was 88.7%, 83%, and 75.5%, respectively, whereas CSS rates were 94.1%, 88.1%, and 78.1%, respectively. In the 45 patients who were treated with curative intent (M0), the OS rates at 1, 3, and 5 years were 91.1%, 88.9%, and 86.7%, respectively; whereas CSS rates were 97.6%, 95.2%, and 90.3%, respectively; and DFS rates were 90.7%, 88.3%, and 88.3%, respectively. We did not find any locoregional failure in patients with M0-status (n=45). Chronic toxicity was rare. KRAS mutations, as detected in 33.3%, showed no correlation with the clinicopathological parameters nor significance for either OS (P=.112), CSS (P=.264), or DFS (P=.565). Conclusions: Taken together, chemoradiation therapy combined with cetuximab is safe, feasible, and offers excellent survival rates. KRAS mutation status was not a predictive factor. Importantly, lack of improvement in pCR rate did not translate to poor survival in our clinical trial.

• OSTI ID: 22278280
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 5 Vol. 87; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

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