Phase I trial of split-dose induction docetaxel, cisplatin, and 5-fluorouracil (TPF) chemotherapy followed by curative surgery combined with postoperative radiotherapy in patients with locally advanced oral and oropharyngeal squamous cell cancer (TISOC-1)

Katrin Oertel, Karin Spiegel, Harald Schmalenberg, Andreas Dietz, Georg Maschmeyer, Thomas Kuhnt, Holger Sudhoff, Thomas G Wendt, Orlando Guntinas-Lichius, Katrin Oertel, Karin Spiegel, Harald Schmalenberg, Andreas Dietz, Georg Maschmeyer, Thomas Kuhnt, Holger Sudhoff, Thomas G Wendt, Orlando Guntinas-Lichius

Abstract

Background: Induction chemotherapy (ICT) with docetaxel, cisplatin and fluorouracil (TPF) followed by radiotherapy is an effective treatment option for unresectable locally advanced head and neck cancer. This phase I study was designed to investigate the safety and tolerability of a split-dose TPF ICT regimen prior to surgery for locally advanced resectable oral and oropharyngeal cancer.

Methods: Patients received TPF split on two dosages on day 1 and 8 per cycle for one or three 3-week cycles prior to surgery and postoperative radiotherapy or radiochemotherapy. Docetaxel was escalated in two dose levels, 40 mg/m2 (DL 0) and 30 mg/m2 (DL -1), plus 40 mg/m2 cisplatin and 2000 mg/m2 fluorouracil per week using a 3 +3 dose escalation algorithm.

Results: Eighteen patients were enrolled and were eligible for toxicity and response. A maximum tolerated dose of 30 mg/m2 docetaxel per week was reached. The most common grade 3+ adverse event was neutropenia during ICT in 10 patients. Surgery reached R0 resection in all cases. Nine patients (50%) showed complete pathologic regression.

Conclusions: A split-dose regime of TPF prior to surgery is feasible, tolerated and merits additional investigation in a phase II study with a dose of 30 mg/m docetaxel per week.

Trial registration number: NCT01108042 (ClinicalTrials.gov Identifier).

Figures

Figure 1
Figure 1
Treatment schedule. TPF, docetaxel+cisplatin+5-fluorouracil; Tox, determination of induction chemotherapy because of toxicity (did not occur).

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