| General information |
| Database: | DB00340 |
| Objective: | To determine the potential efficacy of combining cetuximab with chemotherapy in patients with advanced nodal disease, they conducted a phase II trial with induction chemotherapy (ICT) consisting of six weekly cycles of paclitaxel 135 mg/m(2) and carboplatin (area under the curve = 2) with cetuximab 400 mg/m(2) in week 1 and then 250 mg/m(2) (PCC). |
| Authors: | Kies MS, et al |
| Title: | Induction chemotherapy and cetuximab for locally advanced squamous cell carcinoma of the head and neck: results from a phase II prospective trial. |
| Journal: | J Clin Oncol. |
| Year: | 2010 |
| PMID: | 19917840 |
| Trial Design |
| Clinical Trial Id: | NCT00301028 |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced head and neck squamous cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Induction chemotherapy and cetuximab |
| Study Type: | Phase II Prospective Trial |
| Key Patients Feature: | previously untreated patientswith histologically proven, stage IVA or IVB SCCHN and nodal staging ofN2b/c or N3 (oral cavity, oropharynx, larynx, hypopharynx, and nasopharynx) were entered. Patients have been observed through August 2008.Normal hematopoietic, hepatic, and renal functions were required. |
| Biomarker: | Human Papillomavirus and EGFR expression |
| Biomark Analysis: | Human papillomavirus (HPV) 16, found in 12 (46%) of 26 biopsies, was associated with improved PFS (P = .012) and OS (P = .046);patients with HPVpositive tumors have an excellent prognosis. |
| Control Group Info: | single arm |
| Treatment Info: | induction chemotherapy (ICT) consisting of six weekly cycles of paclitaxel 135 mg/m(2) and carboplatin (area under the curve = 2) with cetuximab 400 mg/m(2) in week 1 and then 250 mg/m(2) (PCC). After ICT, patients underwent riskbased local therapy, which consisted of either radiation, concomitant chemoradiotherapy, or surgery, based on tumor stage and site at diagnosis. |
| Primary End Point: | to increase the overall clinical/radiographic CR rate after ICT from 30% (expected with paclitaxel/carboplatin) to 50% with PCC and to determine toxicity. |
| Secondary End Point: | NA |
| Patients Number: | 47 |
| Trial Results |
| DLT_MTD: | the most common nonhematologic toxicity wasrash/folliculitis (grades 2 and 3 in 38% and 45% of patients, respectively), followed by fatigue, diarrhea, and sensory neuropathy (Table4). The most common grade 2 to 4 hematologic toxicity was neutropenia(grades 2, 3, and 4 in 23%, 19%, and 2% of patients, respectively). |
| Objective Response Rate: | The overall CR rate after completion of radiotherapy, with orwithout chemotherapy, was 70% (95% CI, 55% to 83%), with partial responses in26%of patients. |
| Disease Control Rate: | 0.96 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The 3year progression free survival (PFS) rate was 87% (95% CI, 78% to 97%) |
| Median OS A vs. C: | The 3year overall survival (OS) rate was 91% (95% CI, 84% to 99%). Human papillomavirus (HPV) 16, found in 12 (46%) of 26 biopsies, was associated with improved PFS (P .012) and OS (P .046). |
| Adverse Event(agent arm): | During ICT, the most common nonhematologic toxicity was rash/folliculitis (grades 2 and 3 in 38% and 45% of patients, respectively), followed by fatigue, diarrhea, and sensory neuropathy (Table 4). The most common grade 2 to 4 hematologic toxicity was neutropenia (grades 2, 3, and 4 in 23%, 19%, and 2% of patients, respectively). There were no instances of febrile neutropenia. Dose reductions were needed in one patient for cetuximab and in four and two patients for paclitaxel and carboplatin, respectively. |
| Conclusions: | ICT with weekly PCC followed by riskbased local therapy seems to be feasible, effective, and well tolerated. PFS is promising, and this sequential treatment strategy should be further investigated. Patients with HPV positive tumors have an excellent prognosis. |