| General information |
| Database: | DB00354 |
| Objective: | This multicenterphase II study was undertaken to define the efficacy and safety of cetuximab, an antiepidermal growth factor receptor chimeric human and murine monoclonal antibody, administered with cisplatin to patients with refractory metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN). |
| Authors: | Herbst RS, et al |
| Title: | Platinumbased chemotherapy plus cetuximab in head and neck cancer. |
| Journal: | J Clin Oncol. |
| Year: | 2005 |
| PMID: | 16009949 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced head and neck squamous cell carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Platinumbased chemotherapy plus cetuximab |
| Study Type: | multicenterphase II study |
| Key Patients Feature: | athologically confirmed recurrent squamous cell carcinoma of the oral cavity, pharynx, or larynx considered notcurable with conventional treatment; bidimensionally measurabledisease; Karnofsky performance score (KPS) of 60; prior totalcisplatin exposure 200 mg/m2 at the initiation of the study and 450 mg/m2 after an eligibility amendment (described in Stableand Progressive Disease Cohorts); and neuropathy grade 1 atstudy entry. patients were 18 years of age; had adequate hematologic, hepatic, and renal functions; used effective contraceptionif procreative potential existed; and had sufficient tumor tissueavailable for immunohistochemical determination of EGFR expression |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | patients were to receive two 3week cycles with cisplatin/paclitaxel or cisplatin/fluorouracil. Patients (n = 30) with a complete or partial response continued standard therapy. Seventysix patients with stable disease (SD; n = 51) or progressive disease (PD/1; n = 25) received combination therapy with cetuximab (400 mg/m2 intravenously on day 1, then 250 mg/m2/wk) and cisplatin (75 or 100 mg/m2 intravenously on day 1 every 3 weeks). The protocol was subsequently amended to enroll patients who had developed PD within 90 days after platinumbased therapy (PD/2; n = 54). |
| Primary End Point: | the objective response rate of treatment |
| Secondary End Point: | NA |
| Patients Number: | 132 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Five patients (20%) in PD/1, three patients (6%) in PD/2, and nine patients (18%) with SD achieved an objective response |
| Disease Control Rate: | in the SD cohort, PD/1 and PD/2 cohorts: 76%, 64%, 52% |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | in the SD cohort, PD/1 and PD/2 cohorts (months): 4.9 (95% CI 3.0 to 6.0), 3.0 (95% CI 1.9 to 4.1), 2.0 (95%CI 1.6 to 2.9) |
| Median OS A vs. C: | in the SD cohort, PD/1 and PD/2 cohorts (months): 11.7 (95% CI 8.1 to 14.9), 6.1 (95% CI 2.6 to 7.6), 4.3 (95% CI 3.0 to 5.8) |
| Adverse Event(agent arm): | The most common toxicities were anemia, acnelike skin rash, leukopenia, fatigue and malaise, and nausea and vomiting. Seven patients (5%) developed a grade 3 or 4 hypersensitivity reaction to cetuximab. |
| Conclusions: | Cetuximab and cisplatin is an active regimen in refractory SCCHN. The relative contribution of cetuximab is better defined in a singleagent trial. Cetuximab did not exacerbate cisplatin toxicity but was associated with skin rash in a majority of patients and occasional serious allergic reactions. Further study of this compound is warranted. |