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)
1 Department of Otorhinolaryngology, Jena University Hospital, Lessingstrasse 2, Jena, D-07740, Germany
2 Department of Medicine II, Jena University Hospital, Jena, Germany
3 Department of Otorhinolaryngology/Plastic Surgery, University Hospital Leipzig, Leipzig, Germany
4 Department of Hematology, Oncology & Palliative Care, Klinikum Ernst von Bergmann, Potsdam, Germany
5 Department of Radiation Oncology, University of Rostock, Rostock, Germany
6 Department of Otorhinolaryngology, Head and Neck Surgery, Klinikum Bielefeld, Bielefeld, Germany
7 Department of Radiation Oncology, Jena University Hospital, Jena, Germany
Citation and License
BMC Cancer 2012, 12:483 doi:10.1186/1471-2407-12-483Published: 20 October 2012
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.
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.
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.
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)