OP234: 5-Years’ Results of the German Head and Neck Cooperative Trials Group ARO 04-01 of concurrent 72 Gy HART/cis-Platinum/5-FU vs. HART/Mitomycin/5-FU in LAD H&N cancer

Abstract

Are 6 weekly cycles of cis-Platinum (DDP) plus one cycle of 5-FU with concurrent hyperfractionated radiotherapy (HART) superior to 2 cycles of Mitomycin C (MMC) plus one cycle of 5-FU with HART in terms of overall survival (OS), progression-free (PFS) and metastases-free survival (MFS), local (LC), regional (RC) and loco-regional control (LRC)? Eligibility: Stage IV SCC of the oro- and hypopharynx (OP and HP), KFS of ⩾80% stratified for sites, N-status, grading, haemoglobin and centres. The HART schedule was reported elsewhere (V.Budach, JCO 23; 2005). HART was applied concurrently with DDP/5-FU at 30mg/m2 days 1, 8, 15, 22, 29 and 36 or MMC/5-FU at 10mg/m2 day 1+36 and for both arms with 600mg/m2 5-FU days 1-5 as 120 hrs. continuous infusion. TVD dose prescription was 72 Gy for macroscopic disease, 60 Gy for surrounding nodes of high-risk and 50 Gy of low-risk for microscopic involvement. 3D-conformal or IMRT-TP was used. 364 patients were analysed using the ITT principle. Hazard ratio (HR) calculations were adjusted for competing risk factors. Median follow-up was 54 mos. for both treatment arms. Mean age was 55.4 years, 83% were males and 17% females. All patients had stage IV at diagnosis (UICC 2002). 58.5% suffered from OP-cancer and 41.5% from HP-cancer. The OS, PFS and MFS at 5 years for the DDP-arm was 39.1%, 47.2% and 66.8% versus 32.8% (n.s.), 37.2% (n.s., HR: 0.74, 95%-CI: 0.55-1.00, p=.05) and 53.5% (p=.044, hazard ratio: 0.63, 95% CI: 0.43-0.94, p = 0.023) for the MMC-arm, respectively. The corresponding LC, RC and LRC was 66.2%, 77.3% and 59,1% for the DDP-arm versus 65.9% (n.s), 73.3% (n.s.) and 56.1% (n.s.), for the Mitomycin C arm, respectively. Eight items recorded for acute toxicity (dysphagia, mucositis, dermatitis, xerostomia, pain, weight, leukopenia and creatinine showed no differences between the two treatment arms except for an elevated creatinine level for the DDP-arm (p<.001). Nine items for late morbidity (Dysphagia, Xerostomia, oedema, subcutaneous fibrosis, laryngeal oedema, osteoradionecrosis, plexopathia, L’hermittes syndrome, tracheostomia and PEG showed no significant differences between the treatment arms using nonparametric analyses of variances for repeated measurements. The overall compliance rate for the HART scheme was 96%, DDP: 72%, 5-FU: 97% and MMC: 86%, respectively. This phase III trial first establishes level IB-evidence for a once weekly DDP chemoradiation regimen against two cycles of Mitomycin C. In terms of MFS and DFS @5 yrs., DDP/5-FU HART is superior to MMC/5-FU HART at equal levels of acute and late radiation sequelae for both treatment arms. No significant differences were seen yet for OS, LC, RC or LRC. Chemoradiation with weekly DDP/5-FU or MMC/5-FU shows excellent compliance and can easily compete with other concurrent chemo- or bio-radiation schedules including induction TPF followed by radiation.