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)

doi:10.1186/1471-2407-12-483

BMC Cancer. 2012; 12: 483.

Published online 2012 October 20. doi: 10.1186/1471-2407-12-483

PMCID: PMC3485626

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,¹ Karin Spiegel,¹ Harald Schmalenberg,² Andreas Dietz,³ Georg Maschmeyer,⁴ Thomas Kuhnt,⁵ Holger Sudhoff,⁶ Thomas G Wendt,⁷ and Orlando Guntinas-Lichius¹

¹Department of Otorhinolaryngology, Jena University Hospital, Lessingstrasse 2, Jena, D-07740, Germany

²Department of Medicine II, Jena University Hospital, Jena, Germany

³Department of Otorhinolaryngology/Plastic Surgery, University Hospital Leipzig, Leipzig, Germany

⁴Department of Hematology, Oncology & Palliative Care, Klinikum Ernst von Bergmann, Potsdam, Germany

⁵Department of Radiation Oncology, University of Rostock, Rostock, Germany

⁶Department of Otorhinolaryngology, Head and Neck Surgery, Klinikum Bielefeld, Bielefeld, Germany

⁷Department of Radiation Oncology, Jena University Hospital, Jena, Germany

Corresponding author.

Katrin Oertel: katrin.oertel/at/med.uni-jena.de; Karin Spiegel: karin.spiegel/at/med.uni-jena.de; Harald Schmalenberg: harald.schmalenberg/at/med.uni-jena.de; Andreas Dietz: andreas.dietz/at/medizin.uni-leipzig.de; Georg Maschmeyer: gmaschmeyer/at/klinikumevb.de; Thomas Kuhnt: thomas.kuhnt/at/uni-rostock.de; Holger Sudhoff: holger.sudhoff/at/klinikumbielefeld.de; Thomas G Wendt: thomas.wendt/at/med.uni-jena.de; Orlando Guntinas-Lichius: orlando.guntinas/at/med.uni-jena.de

Received June 22, 2012; Accepted October 18, 2012.

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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)

Keywords: Docetaxel, Cisplatin, 5-fluorouracil, Locally advanced oral cancer, Surgery, Radiotherapy

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