TPF plus cetuximab induction chemotherapy followed by biochemoradiation with weekly cetuximab plus weekly cisplatin or carboplatin: a randomized phase II EORTC trial.
Background
Our aim was to test the safety of cetuximab added to chemoradiation with either cisplatin or carboplatin after prior induction chemotherapy.


Methods
Patients with stage III/IV unresectable, squamous cell carcinoma of the head and neck received up to four cycles of TPF-E (cisplatin and docetaxel 75 mg/m2 on day 1 followed by 5-FU 750 mg/m2/day as a continuous infusion on days 1-5 plus cetuximab at a loading dose of 400 mg/m2 followed by a weekly dose of 250 mg/m2), with prophylactic antibiotics but no growth factors. Patients not progressing after four cycles of TPF-E were randomly assigned to radiotherapy (70 Gy over 7 weeks in 2 Gy fractions) and weekly cetuximab with either weekly cisplatin 40 mg/m2 or carboplatin, AUC of 1.5 mg/ml/min. Primary endpoint was feasibility.


Results
Forty-seven patients were recruited. One patient did not start TPF (hypersensitivity reaction during the cetuximab loading dose). Induction TPF-E was discontinued in 12 patients due to toxicity (6 patients), medical decision (2), death (1), patient refusal (1), protocol violation (1), co-morbidity (1). Three further patients were not randomized [progressive disease (1), protocol violation (1), toxicity and co-morbidity (1)]. Of particular interest are three patients who suffered from bowel perforation, one patient who died as results of pneumonia and septic shock, and a second patient who was found dead at home 12 days after starting TPF-E (cause of death unknown). Weekly cisplatin and carboplatin was stopped early in seven and four patients, respectively. Radiotherapy was stopped in two patients with cisplatin and interrupted in one patient with cisplatin and four patients with carboplatin.


Conclusions
The addition of cetuximab to full dose TPF induction chemotherapy led to unacceptable complications and premature closing of the study. Only 34 out of 46 patients completed four cycles of TPF-E and only 30 started biochemoradiation.
['Specenier|P M|PM|', 'Remenar|E|E|', 'Buter|J|J|', 'Schrijvers|D L|DL|', 'Bergamini|C|C|', 'Licitra|L F|LF|', 'Awada|A|A|', 'Clement|P M|PM|', 'Fortpied|C|C|', 'Menis|J|J|', 'Vermorken|J B|JB|']
D000293:Adolescent D000328:Adult D000368:Aged D000971:Antineoplastic Combined Chemotherapy Protocols D019540:Area Under Curve D016190:Carboplatin D002294:Carcinoma, Squamous Cell D000068818:Cetuximab D059248:Chemoradiotherapy D002945:Cisplatin D004305:Dose-Response Relationship, Drug D005260:Female D005472:Fluorouracil D006258:Head and Neck Neoplasms D006801:Humans D060828:Induction Chemotherapy D008297:Male D008875:Middle Aged D000077195:Squamous Cell Carcinoma of Head and Neck D043823:Taxoids D055815:Young Adult
TPF cetuximab induction chemotherapy biochemoradiation head and neck cancer locoregionally advanced