Rationale for superseding:
There is at present very little evidence to show that results of induction chemotherapy followed by bioradiotherapy is superior to induction chemotherapy followed by radiotherapy alone. It is not supported by any international guidelines in this setting. For this reason the protocol has been superseded by the medical oncology reference committee.
The evidence supporting the use of this protocol comes from a small retrospective, multicenter phase II trial by Buiret et al. Clinical data from 46 patients with stage III or IV non metastatic SCCHN who received docetaxel, cisplatin, 5FU as induction chemotherapy (ICT) followed by external radiotherapy (ERT) with concomitant cetuximab were analysed. Patients received ICT consisting of docetaxel (day 1, 75 mg/m2), cisplatin (day 1, 75 mg/m2) and 5FU (days 1 to 5, 750 mg/m2) every 21 days for 3 to 4 cycles. Following ICT, patients were treated with weekly cetuximab (400 mg/m2 loading dose; 250 mg/m2 subsequent doses) with concurrent radiotherapy for 7 to 8 cycles.r
The primary endpoint was the tolerability of the treatments, in particular the proportion of patients who completed the study protocol. The secondary endpoint was safety. Future prospective studies are required to evaluate the efficacy of this protocol.r
The results of a phase II TREMPLIN study comparing concurrent chemoradiotherapy with cisplatin or cetuximab following ICT was presented at ASCO 2011. A total of 116 patients were randomised to receive cisplatin 100 mg/m2 d1, 22, 43 with RT (n=60) or cetuximab 400 mg/m2 loading dose followed by 250 mg/m2 weekly with RT (n=56). The primary end point was larynx preservation (LP) at 3 months after treatment and secondary end points were larynx function preservation (LFP) at 18 months after treatment, survival, feasibility of salvage surgery and tolerance to treatment.r
In the trial by Buiret, the percentage of patients completing ICT was 73.9%, ERT 93.5%, and cetuximab 69.9%. ICT was better tolerated than previously reported.r In the TREMPLIN study, after a mean follow-up of 32 months, LFP and survival were similar in both arms, acute and late toxicity were more common in the cisplatin/RT arm. Local failures occurred more often in the cetuximab/Rt arm but salvage surgery was only feasible in the cetuximab arm resulting in similar overall local control.r
The rates of temporary suspensions of radiation (39.1%, mean duration of 13 days) and hospitalisation (26.1%) during ERT with concomitant cetuximab were high. Weight loss during treatment (21.4% of patients lost >10% of their body weight), radiodermatitis, and radiomucositis were the main causes of temporary suspension of treatment. There were no grade 4 dermatitis or allergic reactions to cetuximab.r