Cetuximab in Combination With Capecitabine, Oxaliplatin, and Concomitant Radiotherapy (Cet-Capox-RT) as Preoperative Therapy for Rectal Cancer

Reviewer: Christopher Dolinsky, MD
University of Pennsylvania School of Medicine
Last Modified: November 8, 2006

Presenter: C. Roedel
Presenter's Affiliation: Universityeristat Erlangen, Erlangen, Germany
Type of Session: Scientific


  • Cetuximab is a monoclonal antibody to the EGF-receptor.
  • Cetuximab has been shown to improve outcomes in metastatic colorectal cancer.
  • Cetuximab in combination with radiation therapy has been shown to improve outcomes in head and neck cancers.
  • Previous research has demonstrated that tumors that overexpress EGFR are less likely to respond to preoperative radiation therapy.
  • A multicenter trial was undertaken to evaluate the safety and efficacy of a regimen containing capecitabine, oxaliplatin, and cetuximab in combination with radiation, all given before surgical resection of locally advanced and/or low-lying rectal cancers.

Materials and Methods

  • This study was a multicenter phase I/II trial.
  • Patients who were eligible had clinical stage T3-T4 and/or N+ disease.
  • Patients with metastatic disease were eligible, and 20% of patients analyzed did have metastatic disease.
  • The phase I part of the study was performed to elucidate the dose-limiting toxicity and maximally tolerated dose (MTD) of capecitabine (doses from 1000-1300-1650 mg/m2).
  • The phase II part of the study was performed to assess the pathologic complete response rate (pCR), with >30% pCR rate considered “very interesting”, and <15% pCR rate considered “futile”.
  • 13 patients were enrolled in the phase I section of the trial.
  • 43 patients were enrolled in the phase II section of the trial.
  • Cetuximab was given at 400mg/m2, starting 7 days before radiation, and then in 6 weekly doses of 250mg/m2 during radiation.
  • 1.8 Gy radiation fractions were used to a dose of 50.4 Gy.
  • Oxaliplatin was given at a dose of 50 mg/m2 on days 1, 8, 22, and 29.
  • Capecitabine was given at the three dose levels BID, from days 1-14 and days 22-35.


  • In the phase I study, a dose-limiting toxicity was seen in one patient at dose level 1 (grade 3 or 4 diarrhea).
  • In the phase I study, cetuximab was stopped in one patient who achieved a grade 2 hypersensitivity reaction.
  • Full doses of the respective agents were administered in all patients, except the one with dose- limiting toxicity.
  • There were 2 deaths, one from multi-organ system failure and another from a cardiac event 4 weeks post-completion of chemoradiotherapy.
  • For all patients treated, the overall complication rate was 46%, with the most common complications being wound healing (17%) and anastamotic leak (11%).
  • A path CR was seen in 9% of patients, compared with 18% in a previous study of capcitabine/oxaliplatin without cetuximab, performed by the same authors.

Author's Conclusions

  • CAPOX+RT+Cet is a feasible and well-tolerated regimen.
  • The pCR rates do not suggest enhanced efficacy as compared to CAPOX-RT alone.
  • The rationale of CAPOX-RT-Cet seems convincing, but further studies should define the best sequence for this regimen.

Clinical/Scientific Implications

The authors present an interesting phase I/II trial that incorporated a novel biologic agent into an established chemotherapy regimen.  Somewhat surprisingly, the pCR rate with this combination appears to be inferior to capecitabine/oxalplatin/RT.  Further research should attempt to figure out which patients might benefit from cetuximab as a part of their regimen. It may be the case that this drug only benefits a subset of patients with a particular molecular signature.  It also may be the case that cetuximab is more active with radiation alone that in combination with radiation and chemotherapy.  Regardless, these data need be verified and repeated, as it would be premature to abandon this compound in rectal cancer just yet.