| General information |
| Database: | DB00349 |
| Objective: | This was an open, randomized, multicenter, phase I/II study to investigate the safety and tolerability of cetuximab in the firstline treatment of recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN). |
| Authors: | Bourhis J, et al |
| Title: | Phase I/II study of cetuximab in combination with cisplatin or carboplatin and fluorouracil in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. |
| Journal: | J Clin Oncol. |
| Year: | 2006 |
| PMID: | 16717293 |
| 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: | cetuximab + cisplatin or carboplatin and fluorouracil |
| Study Type: | open, randomized, multicenter, phase I/II study |
| Key Patients Feature: | included 18yearsofage;recurrentormetastaticSCCHNnotsuitablefor local therapy; disease measurable by computed tomography or magneticresonance imaging; life expectancy 3 months at study entry; tumor tissueavailableforimmunohistochemistrystainingforEGFRexpression;Karnofskyperformancestatus 70%atstudyentry;adequatehematologic, hepatic, andrenal function; and recovery from relevant toxicities of previous treatment. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Treatment comprised cetuximab (initial dose 400 mg/m2 with subsequent weekly doses of 250 mg/m2) in combination with 3week cycles of either cisplatin (100 mg/m2) or carboplatin (area under the curve, 5), each in combination with a 5day infusion of fluorouracil (FU) at escalating doses of 600, 800, and 1, 000 mg/m2/d. The study was divided into twophases: A, the first two cycles (6 weeks) focusing on the safety and tolerability of combination therapy; and B, the remaining time for those benefiting from therapy until disease progression or intolerable toxicity. |
| Primary End Point: | the safety and tolerability |
| Secondary End Point: | the PK, the best overall response, the time to progression and overall survival time. |
| Patients Number: | 43 |
| Trial Results |
| DLT_MTD: | The frequency of DLTs experienced during phase A is summarized in Table 2. At the highest dose level of FU, four of 12 patients(33%) in the cisplatin group and two of 12 (17%) in the carboplatin group experienced a DLT, both of which are considered to be within the acceptable tolerability limit |
| Objective Response Rate: | The overall response rateamong patients was 36% |
| Disease Control Rate: | 74% (95% CI, 60% to 85%) |
| Median Time to Progression: | 155 days (95% CI, 127 to 186 days) for the two groups, 183 days (95% CI, 86 to 189 days) in the cisplatin group, and 151 days (95% CI, 127 to 189 days) in the carboplatin group. |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | 297 days (95% CI, 242 to 418 days) for the two groups, 324 days (95% CI, 229 to 418 days) in the cisplatin groupand260 days(95% CI, 238 days to not estimable) in the carboplatin group. |
| Adverse Event(agent arm): | The most common grade 3/4 adverse events in both groups were leucopenia (38%), asthenia (25%), vomiting (14%), and thrombocytopenia (15%), which are consistent with the known safety profiles of cetuximab, cisplatin/carboplatin, and FU. |
| Conclusions: | The combination of cetuximab, cisplatincarboplatin, and FU was reasonably well tolerated and active in recurrentmetastatic SCCHN, and merits additional investigation. An FU dose of 1,000 mgm2d in combination with cisplatin or carboplatin can be recommended for additional studies. |