Docetaxel induction therapy in locally advanced squamous cell carcinoma of the head and neck

Abstract

Patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) are often treated with induction chemotherapy or chemoradiotherapy, but to date without major impact on survival. The combination of cisplatin -5-fluorouracil (5-FU) (PF) has been used as standard induction therapy; however, poor patient survival has stimulated investigation into new agents with potential activity in SCCHN. Docetaxel has significant single-agent activity in SCCHN and has been investigated in combination with PF regimens as induction therapy. The results of six phase II studies of docetaxel -PF regimens (TPF) as induction in locally advanced SCCHN patients are reviewed and reported. Consistently, high 2-year survival rates and overall response rates were demonstrated across the phase II trials in the range 42 -82 and 71 -100%, respectively. The toxicity profile seen with TPF-based regimens was acceptable. The primary toxicity was neutropenia, which together with gastrointestinal complaints accounted for the majority of adverse events. Given the encouraging phase II experience with TPF-based regimens, two large-scale phase III studies comparing TPF-based regimens with standard PF regimens are underway. The results have significant potential for validating the findings of the phase II studies, demonstrating improved survival and overall response of patients treated with docetaxel-based induction chemotherapy.

Induction chemotherapy with TPF (Docetaxel, Carboplatin and Fluorouracil) in the treatment of locally advanced squamous cell carcinoma of the head and neck

“…One study group reported for instance that 89% of all biopsies of the primary tumor were negative after three cycles of TPF (22). However, in our study patients received a lower concentration of 5-FU and we administered Carboplatin instead of Cisplatin (18,(20)(21)(22), which might be a possible reason for the lower response rate of our collective.…”

“…Recently it has been shown that ICT using the combination of the taxane Docetaxel with Cisplatin, 5-Fluorouracil (5-FU) provides a significant survival benefit over Cisplatin, 5-Fluorouracil, when used before either definitive RT (TAX323 trial) or Carboplatin-based concomitant chemoradiotherapy (CCRT), especially in reduction of locoregional failure and organ preservation in larynx and hypopharyngeal tumors. Furthermore, the Tax323 study showed a reduction in toxicity and in mortality of 27% (18) and a prolongation of the 3-year survival rate of 37 vs. 26% for TPF and PF-ICT (18,20,21).…”

“…Less mucositis, vomiting and nausea and less hearing loss, fewer toxic deaths were reported within the TPF arm. The TPF ICT was associated with more neutropenia and neutropenic fever (18,(20)(21)(22).…”

“…High response rates in primary sites and longterm survival in curative phase II studies was reported to be 40-80% in different groups of patients (14)(15)(16)(17). Studies of Posner and Vermorken et al showed in the phase III studies TAX 323/324 the improvement of loco-regional control, survival, elimination of distant metastasis, reduced toxicity by implementation of Docetaxel within the ICT regimen compared to PF (18)(19)(20)(21).…”

Docetaxel-loaded liposomes: preparation, pH sensitivity, Pharmacokinetics, and tissue distribution

“…DTX exerts lethal effects on dividing cancer cells by various mechanisms, all of which result in failure of the cell to divide or subsequently to grow and develop (Hanauske et al, 1994;Friedenberg et al, 2003;Herbst and Khuri, 2003;Vassilomanolakis et al, 2005). Thus, DTX plays an important role in the treatment of solid tumors and has been applied in clinical trials against ovarian carcinoma, breast, lung and head/neck cancers (Bissery, 1995;Posner and Lefebvre, 2003;Yang et al, 2011). It has been reported that DTX is more effective and safer than paclitaxel (Grant et al, 2003).…”