| General information |
| Database: | DB00730 |
| Objective: | Thisphase II study investigated the efficacy and safety of cetuximab combined with standard oxaliplatinbased chemotherapy (infusional fluorouracil, leucovorin, and oxaliplatin [FOLFOX4]) in the firstline treatment of epidermal growth factor receptorexpressing metastatic colorectal cancer (mCRC). |
| Authors: | Tabernero J, et al |
| Title: | Phase II trial of cetuximab in combination with fluorouracil, leucovorin, and oxaliplatin in the firstline treatment of metastatic colorectal cancer. |
| Journal: | J Clin Oncol. |
| Year: | 2007 |
| PMID: | 18024868 |
| 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: | 2 |
| Therapeutic Combination Content: | cetuximab + fluorouracil, leucovorin, and oxaliplatin |
| Study Type: | a multicenter, noncontrolled, openlabel, phase II study |
| Key Patients Feature: | patients were eligible if they were 18 years old; had histologicallyconfirmed, nonresectable, EGFRexpressing mCRC with at least one radiologically measurable lesion; an Eastern Cooperative Oncology Group performance status 2 (or for those 75 years, a performance status of 0); andadequate hepatic, renal, and bone marrow functions. patients were ineligible ifthey had a history of previous exposure to EGFRtargeted therapy, previouschemotherapy for mCRC, or uncontrolled severe organ/metabolic dysfunction. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | In the clinical study, patients with mCRC received on day 1 of a 14 day cycle, cetuximab (initial dose 400 mg/m(2) during week 1, then 250 mg/m(2) weekly) followed by FOLFOX4 (oxaliplatin 85 mg/m(2) on day 1; leucovorin 200 mg/m(2) on days 1 and 2, followed by fluorouracil 400 mg/m(2) bolus then 600 mg/m(2) intravenous infusion during 22 hours on days 1 and 2). |
| Primary End Point: | best overall (confirmed) response |
| Secondary End Point: | progression free survival time (PFS), duration of response(DOR), overall survival (OS), and the safety of the combination. |
| Patients Number: | 43 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Thirtyfour objectiveresponses were observed (four CRs and 30 PRs), yielding an overallresponse rate of 79%. Thirtyone responses (four CRs and 27 PRs)were confirmed subsequently, to provide a best overall confirmedresponse rate of 72% |
| Disease Control Rate: | 95%; 95% CI:84 to 99% |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 12.3 months. 95% CI: 7.7 to 15.8 |
| Median OS A vs. C: | 30.0 months. 95% CI: 17.8 to 33.8 |
| Adverse Event(agent arm): | The most commonly reported grade 3/4 AEs (Table 4) werediarrhea (11 patients), neutropenia (10 patients), and paresthesia (eight patients). The most frequently observed skin reaction in the current study was rash, which was seen in 23 patients (53%; grade 3 in seven patients; 16%). Other common adverse effects (all grades) associated with cetuximab treatment, such as dry skin (19 patients; 44%), conjunctivitis (15 patients; 35%), skin fissures (14 patients; 33%), and paronychia (12 patients; 28%) were also observed. |
| Conclusions: | Cetuximab in combination with FOLFOX4 is a highly active firstline treatment for mCRC, showing encouraging RR, mPFS, and mOS values. The treatment resulted in a high resectability rate, which could potentially result in an improved cure rate. This combination is underphase III development. |