The EXTREME regimen, which includes 5-fluorouracil (5-FU), platinum-based chemotherapy, and cetuximab, is a standard of care for patients with recurrent, metastatic squamous cell carcinoma of the head and neck (SCCHN). Unfortunately, this regimen is often associated with high-grade toxicity that may lead to treatment discontinuation. In an attempt to identify a potentially less toxic treatment alternative, a phase II study examined the safety and efficacy of weekly docetaxel, platinum, and cetuximab (TPC) in 27 patients with recurrent, metastatic SCCHN.
Patients were treated with docetaxel (30 mg/m2), cisplatin (30 mg/m2) or carboplatin (area under the curve [AUC] 2), and cetuximab (250 mg/m2) weekly for 3 weeks of a 4-week cycle. The objective response rate (ORR) was 56%, including 3% complete response and 52% partial response. Estimated median progression-free survival (PFS) was 4.8 months, and median overall survival (OS) was 14.7 months. These efficacy data compare favorably with results from the pivotal randomized clinical trial evaluating the EXTREME regimen in first-line treatment of recurrent/metastatic SCCHN.
Importantly, TPC was associated with lower rates of grade 4 adverse events (AEs) than historically seen with chemotherapy doublets and triplets administered three weekly, where grade 4 AEs occur in 30% to 50% of patients. Specifically, with TPC, the only grade 4 AEs were 2 cases of clinically insignificant lymphopenia (7%). Grade 3 events occurred in 85% of patients, and the most common grade 3 AEs occurring in >10% of patients were elevated liver enzymes (22%), mucositis (15%), lymphocytopenia (70%), and acneiform rash (19%). The investigators noted, that while preliminary, these data are very promising and justify further development of the regimen. Given the favorable toxicity profile, the authors suggest testing TPC regimen in combination with immunotherapy in order to maximize efficacy and tolerability.