Chemotherapy for recurrent, metastatic squamous cell carcinoma of the head and neck (SCCHN) may not need not be as toxic as the current standard of care, according to a study published in The Oncologist. The study evaluated a new regimen of weekly docetaxel, cisplatin, and cetuximab.
The standard of care for treating recurrent metastatic SCCHN is the EXTREME regimen, which includes 5-fluorouracil (5-FU), platinum-based chemotherapy, and cetuximab. It is associated with high-grade toxicity that may lead to treatment discontinuation.
In an attempt to identify a potentially less toxic treatment alternative, Vanessa Trieu, from the Larner College of Medicine at the University of Vermont in Burlington, VT, and colleagues examined the safety and efficacy of weekly docetaxel, platinum, and cetuximab (TPC) in 27 patients with recurrent metastatic SCCHN.
Eligible patients with metastatic or recurrent SCCHN with an Eastern Cooperative Oncology Group (ECOG) performance status < 3 were enrolled in the phase 2 trial. Although prior palliative chemotherapy was not permitted, previous chemoradiation, radiation, and/or surgery was permitted if three months had elapsed since the end of the potentially curative treatment.
The TPC regimen consisted of cisplatin 30 mg/m2 or carboplatin AUC2, docetaxel 30 mg/m2, and cetuximab 250 mg/m2 weekly for three weeks in a 28-day cycle. Dose modifications were clearly defined in the protocol and were based on individual toxicity; however, no dose re-escalations were permitted.
Patients were formally evaluated for treatment-related adverse events (AEs) from the time of their first dose of TPC. Tumor response and progression were evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) guideline. Patients were assessed for response every eight weeks ± one week.
The primary objective was to determine the overall response rate to TPC. Secondary endpoints included achieved dose intensity, progression-free survival (PFS), overall survival (OS), and toxicity. Patients who received at least one cycle of weekly TPC were deemed to be evaluable for response.
A response rate was noted in 56% of patients (15/27), and 33% (9/27) had responses confirmed with follow-up imaging per RECIST. These results compared favorably with benchmark studies that evaluated regimens of platinum, fluorouracil, and cetuximab (PFC) and platinum and paclitaxel (PT).
The median PFS—defined as the interval from first chemotherapy treatment to progression of disease—was 4.8 months. The OS, defined as first chemotherapy treatment to death was 14.7 months. These values are also similar to other regimens used in this setting.
There was a very low incidence of high-grade AEs; remarkably, there were only two grade 4 AEs. Both cases were clinically insignificant lymphopenia. This incidence rate compares favorably with prior studies, in which grade 4 AE rates ranged from 30% to 50% for chemotherapy doublets and triplets administered every 21 days.
The investigators point out that the low incidence of AEs is encouraging. It may be due to the substitution of a taxane for fluorouracil, the weekly dosing schedule, and more frequent monitoring, as well as increased attention to supportive care for patients in the study.
“Weekly docetaxel, cisplatin, and cetuximab is an effective regimen for patients with metastatic or recurrent SCCHN. Response rates, PFS, and OS compare favorably with other combination chemotherapy treatments,” wrote the authors.
They concluded: “Grade 4 toxicity rates observed in this study were substantially lower than those described with regimens using less frequent, higher-dose chemotherapy schedules.”
The researchers note that new immunotherapy is changing the landscape of treatment options in patients with head and neck cancer, therefore it is difficult to predict the role of chemotherapy in future clinical practice.
To read more about this study, click here.