| General information |
| Database: | DB00732 |
| Objective: | To assess the safety and preliminary efficacy of concurrent radiotherapy, capecitabine, and cetuximab in the preoperative treatment of patients with rectal cancer. |
| Authors: | Machiels JP, et al |
| Title: | Phase I/II study of preoperative cetuximab, capecitabine, and external beam radiotherapy in patients with rectal cancer. |
| Journal: | Ann Oncol. |
| Year: | 2007 |
| PMID: | 17208931 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced colorectal cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | preoperative cetuximab, capecitabine, and external beam radiotherapy |
| Study Type: | Phase I/II study |
| Key Patients Feature: | patients had a histologically proven rectal adenocarcinomastage T3-T4 and/or N1-N2 by transrectal ultrasound. Other inclusioncriteria were as follows: age >18 years; Eastern Cooperative OncologyGroup (ECOG) performance status of two or less; signed informed consent;and acceptable liver, renal, and hematological parameters: granulocytes>1500/mm3, platelets >100 000/mm3, bilirubin ¡ê1. upper limit of normal(ULN), aspartate aminotransferase/alanine aminotransferase ¡ê2.5. ULN, creatinine ¡ê1.5 mg/dl or creatinine clearance at least 60 ml/min. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | pts received preoperative radiotherapy (1.8 Gy, 5 days/week for 5 weeks, total dose 45 Gy, threedimensional conformal technique) in combination with cetuximab [initial dose 400 mg/m(2) intravenous given 1 week before the beginning of radiation followed by 250 mg/m(2)/week for 5 weeks] and capecitabine for the duration of radiotherapy (650 mg/m(2) orally twice daily, first dose level; 825 mg/m(2) twice daily, second dose level). |
| Primary End Point: | (i) the recommended dose of capecitabine in combination with cetuximab and radiotherapy in the preoperative treatment of rectal cancer;(ii) the feasibility of this preoperative regimen;(iii) the histopathological response rate. |
| Secondary End Point: | NA |
| Patients Number: | 40 |
| Trial Results |
| DLT_MTD: | No DLT was recorded inthese first four patients and so the dose of capecitabine wasescalated to 825 mg/m2 (twice daily) in six patients. Again, noDLT was observed. |
| Objective Response Rate: | Three patients were not assessable for pathologicallydocumented response (pathological response) because they didnot undergo surgery (one disease progression, one death, andone unresectable disease found at surgery). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most frequent grade 1/2 sideeffects were acneiform rash (87%), diarrhea (65%), and fatigue (57%). Grade 3 diarrhea was found in 15%. Three grade 4 toxic effects were recorded: one myocardial infarction, one pulmonary embolism, and one pulmonary infection with sepsis. Two patients (5%) had a pathological complete response. |
| Conclusions: | Preoperative radiotherapy in combination with capecitabine and cetuximab is feasible with some patients achieving pathological downstaging. |