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).
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.


BACKGROUND
NCT01108042 (ClinicalTrials.gov Identifier).
Department of Otorhinolaryngology, Jena University Hospital, Lessingstrasse 2, Jena, D-07740, Germany.
Katrin
K
Oertel
Karin
K
Spiegel
Harald
H
Schmalenberg
Andreas
A
Dietz
Georg
G
Maschmeyer
Thomas
T
Kuhnt
Holger
H
Sudhoff
Thomas G
TG
Wendt
Orlando
O
Guntinas-Lichius
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D060828:Induction Chemotherapy; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
D043823:Taxoids; D000077143:Docetaxel; D002945:Cisplatin; D005472:Fluorouracil