| General information |
| Database: | DB00346 |
| Objective: | They investigated the efficacy of cetuximab plus platinumbased chemotherapy as firstline treatment in patients with recurrent or metastatic squamouscell carcinoma of the head and neck. |
| Authors: | Vermorken JB, et al |
| Title: | Platinumbased chemotherapy plus cetuximab in head and neck cancer. |
| Journal: | N Engl J Med. |
| Year: | 2008 |
| PMID: | 18784101 |
| Trial Design |
| Clinical Trial Id: | NCT00122460 |
| 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: | a phase III study |
| Key Patients Feature: | patients were eligible if they were 18 years of ageor older and had histologically or cytologically confirmed recurrent or metastatic squamouscell carcinoma of the head and neck. Other inclusion criteria included ineligibility for local therapy; at leastone lesion that was bidimensionally measurable bycomputed tomography (CT) or magnetic resonanceimaging (MRI); a Karnofsky performance score of70 or more (on a scale of 0 to 100, with higherscores indicating better performance); adequatehematologic, renal, and hepatic function; and tumor tissue that was available for evaluation of EGFRexpression. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | A: platinumbased chemotherapy plus fluorouracil alone B:cetuximab plus platinumfluorouracil chemotherapy |
| Treatment Info: | patients were assigned to receive cisplatin (at a dose of 100 mg per square meter of bodysurface area on day 1) or carboplatin (at an area under the curve of 5 mg per milliliter per minute, as a 1hour intravenous infusion on day 1) plus fluorouracil (at a dose of 1000 mg per square meter per day for 4 days) every 3 weeks for a maximum of 6 cycles and 222 patients to receive the same chemotherapy plus cetuximab (at a dose of 400 mg per square meter initially, as a 2hour intravenous infusion, then 250 mg per square meter, as a 1hour intravenous infusion per week) for a maximum of 6 cycles. Patients with stable disease who received chemotherapy plus cetuximab continued to receive cetuximab until disease progression or unacceptable toxic effects, whichever occurred first. |
| Primary End Point: | overall survival. |
| Secondary End Point: | progression free survival, the best overall response, disease control, the time to treatment failure, the duration of the response, and safety. |
| Patients Number: | 442 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | The addition of cetuximab prolonged the median progression free survivaltime from 3.3 to 5.6 months (hazard ratio for progression, 0.54; P<0.001) and increased the response rate from 20% to 36% (P<0.001). |
| Disease Control Rate: | Cetuximab plus Platinum-Fluorouracil arm: 81%; Platinum-Fluorouracil Alone arm: 60% |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The addition of cetuximab prolonged the median progression free survival time from 3.3 to 5.6 months (hazard ratio for progression, 0.54; P<0.001) |
| Median OS A vs. C: | 7.4 months in the chemotherapyalone group to 10.1 months in the group that received chemotherapy plus cetuximab (hazard ratio for death, 0.80; 95% confidence interval, 0.64 to 0.99; P = 0.04). |
| Adverse Event(agent arm): | The most common grade 3 or 4 adverse events in the chemotherapyalone and cetuximab groups were anemia (19% and 13%, respectively), neutropenia (23% and 22%), and thrombocytopenia (11% in both groups). Sepsis occurred in 9 patients in the cetuximab group and in 1 patient in the chemotherapyalone group (P = 0.02). Of 219 patients receiving cetuximab, 9% had grade 3 skin reactions and 3% had grade 3 or 4 infusionrelated reactions. There were no cetuximabrelated deaths. |
| Conclusions: | As compared with platinumbased chemotherapy plus fluorouracil alone, cetuximab plus platinumfluorouracil chemotherapy improved overall survival when given as firstline treatment in patients with recurrent or metastatic squamouscell carcinoma of the head and neck. |