TPF plus cetuximab induction chemotherapy followed by biochemoradiation with weekly cetuximab plus weekly cisplatin or carboplatin : a randomized phase II EORTC trial.
Mené sur 47 patients atteints d'un carcinome épidermoïde de la tête et du cou non résécable de stade III/IV, cet essai de phase II évalue la possibilité, en termes de toxicité, d'ajouter le cétuximab à une chimiothérapie d'induction de type TPF (cisplatine, docétaxel et fluorouracile), suivie par une radiothérapie et un traitement hebdomadaire par cétuximab et cisplatine ou carboplatine
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 4 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 day 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 4 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 7 and 4 patients, respectively. Radiotherapy was stopped in 2 patients with cisplatin and interrupted in 1 patient with cisplatin and 4 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 4 cycles of TPF-E and only 30 started biochemoradiation.