Concurrent chemo-radiation is a larynx preserving strategy. The key evidence supporting this strategy comes from RTOG 91.11 which compared induction cisplatin/fluorouracil (PF) followed by RT (control arm), concomitant cisplatin/RT, or RT alone.r At the last up date of this trial, 520 patients with a median follow up of 10.8 years were alive and were analysed. This study demonstrated improved loco-regional control and larynx preservation in the concurrent arm. CRT resulted in 41% reduction in risk of loco-regional failure compared with RT alone (HR, 0.59; 95% CI, 0.43 to 0.82; P=0.0015) and 34% reduction compared to induction chemotherapy (HR, 0.66; 95% CI, 0.48 to 0.92; P=0.0037). The laryngectomy free survival was similar in both arms that received chemotherapy. There was no overall survival difference between the three arms.
Concurrent chemoradiation therapy offers a higher chance of larynx preservation than radiotherapy alone or induction chemotherapy followed by radiation. The best available evidence supports the use of cisplatin as the drug of choice in this setting. In patients unsuitable for cisplatin based chemotherapy, cetuximab is a suitable alternative for concurrent treatment with radiotherapy.rr In a phase III RCT, cetuximab conferred a 9% absolute survival benefit (36.4% vs. 45.6%) at 5 years when compared to radiotherapy alone in locally advanced head and neck squamous cell cancers.r
Similarly, the VA laryngeal cancer study group showed no clear detriment with induction chemotherapy followed by chemoradiation as opposed to induction chemotherapy followed by surgery and radiotherapy.r The 2-year overall survival was the same (68%) with a laryngeal preservation rate of 64%.
Four studies investigating induction chemotherapy failed to accrue patients and were underpowered.rrrr There is insufficient evidence to indicate that survival or larynx-preservation is improved with induction chemotherapy before concurrent treatment, however; it may be considered in patients with bulky disease.
Peters et al. 2010 reported on the impact of radiotherapy quality on patient outcomes in a large international phase III trial (TROG 02.02).r In patients with major deficiencies in their treatment compared to those whose treatment was initially protocol compliant they reported a significantly inferior outcome; 2 years overall survival of 50% vs 70%; hazard ratio (HR), 1.99; P< 0.001; and 2 years freedom from locoregional failure, 54% v 78%; HR, 2.37; <P 0.001, respectively. These results show the critical importance of radiotherapy quality on outcome of chemoradiotherapy in locally advanced head and neck cancer.