Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer.
BACKGROUND
Phase 2 studies suggest that the standard regimen of cisplatin and fluorouracil (PF) plus docetaxel (TPF) improves outcomes in squamous-cell carcinoma of the head and neck. We compared TPF with PF as induction chemotherapy in patients with locoregionally advanced, unresectable disease.


METHODS
We randomly assigned eligible patients between the ages of 18 and 70 years who had stage III or stage IV disease and no distant metastases to receive either TPF (docetaxel and cisplatin, day 1; fluorouracil by continuous infusion, days 1 to 5) or PF every 3 weeks for four cycles. Patients without progression of disease received radiotherapy within 4 to 7 weeks after completing chemotherapy. The primary end point was progression-free survival.


RESULTS
A total of 358 patients underwent randomization, with 177 assigned to the TPF group and 181 to the PF group. At a median follow-up of 32.5 months, the median progression-free survival was 11.0 months in the TPF group and 8.2 months in the PF group (hazard ratio for disease progression or death in the TPF group, 0.72; P=0.007). Treatment with TPF resulted in a reduction in the risk of death of 27% (P=0.02), with a median overall survival of 18.8 months, as compared with 14.5 months in the PF group. There were more grade 3 or 4 events of leukopenia and neutropenia in the TPF group and more grade 3 or 4 events of thrombocytopenia, nausea, vomiting, stomatitis, and hearing loss in the PF group. The rates of death from toxic effects were 2.3% in the TPF group and 5.5% in the PF group.


CONCLUSIONS
As compared with the standard regimen of cisplatin and fluorouracil, induction chemotherapy with the addition of docetaxel significantly improved progression-free and overall survival in patients with unresectable squamous-cell carcinoma of the head and neck. (ClinicalTrials.gov number, NCT00003888 [ClinicalTrials.gov].).
Vermorken
Jan B
JB
Department of Medical Oncology, Universitair Ziekenhuis Antwerpen, Edegem, Belgium. jan.b.vermorken@uza.be
Remenar
Eva
E
van Herpen
Carla
C
Gorlia
Thierry
T
Mesia
Ricard
R
Degardin
Marian
M
Stewart
John S
JS
Jelic
Svetislav
S
Betka
Jan
J
Preiss
Joachim H
JH
van den Weyngaert
Danielle
D
Awada
Ahmad
A
Cupissol
Didier
D
Kienzer
Heinz R
HR
Rey
Augustin
A
Desaunois
Isabelle
I
Bernier
Jacques
J
Lefebvre
Jean-Louis
JL
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D002945:Cisplatin / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011878:Radiotherapy / Q000009:adverse effects; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage*
D043823:Taxoids; D000077143:Docetaxel; D002945:Cisplatin; D005472:Fluorouracil