Five years' results of the German ARO 04-01 trial of concurrent 72 Gy hyperfractionated accelerated radiation therapy (HART) plus once weekly cisplatinum/5-FU versus mitomycin C/5-FU in stage IV head and neck cancer.

Abstract

5512 Background: Are 6 cycles of once weekly DDP plus one cycle of 5-FU with concurrent HART superior to 2 cycles of MMC plus one cycle of 5-FU in terms of overall survival (OS) and metastases-free survival (MFS)? Methods: Eligibility: Stage IV SCC of oro(OP)- and hypopharynx(HP), KFS of ≥80% stratified for sites, N-status, grading, hemoglobin and center. The HART schedule was reported elsewhere (V.Budach, JCO 23;2005). HART was applied concurrently with DDP/5-FU at 30mg/m² days 1,8,15,22,29,36 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. c.i. TVD dose prescription was 72 Gy using 3D-conformal or IMRT-TP. 364 patients were analysed using an ITT principle for OS, MFS, progression-free survival (PFS) and loco-regional control (LRC). Hazard ratio (HR) calculations were adjusted for competing risk factors. Results: Median follow-up was 48 mos. for both arms. Mean age was 55.4 years, 83/17% were male/female and 100% stage IV patients (UICC 2002). 58.5%/41.5% of all patients suffered from OP- or HP cancer, respectively. The OS and MFS at 4 years for the DDP- versus MMC-arm was 42.1% vs. 38.8% (n.s.) and 67.3% vs. 56.6% (p=.05), respectively. The LRC and PFS for the DDP versus MMC-arm was 58.6% vs. 57.2% (n.s.) and 46.4% vs. 38.7% (n.s.). Seven items recorded for acute toxicity and 9 for late morbidity showed no significant differences between the treatment arms except for creatinine for the DDP-arm (p < 0.001) using nonparametric analyses of variances for repeated measurements. The overall compliance rates for RTX were 96%, DDP: 72%, 5-FU: 97%, MMC: 86%, respectively. Conclusions: This phase III trial first establishes level IB-evidence for a once weekly DDP chemoradiation regimen. For MFS at 4 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, PFS or LRC. Chemoradiation with weekly DDP/5-FU or MMC/5-FU shows excellent compliance rates and can easily compete with other concurrent chemo- or bio-radiation schedules including induction TPF followed by radiation.

Total Laryngectomy—Still Cutting-Edge?

“…In the absence of contraindications, cisplatin-based chemotherapy, e.g., with 5-fluoruracil, is to be recommended. Alternatives include the use of carboplatin with/without 5-fluoruracil, of mitomycin C with/without 5-fluoruracil, or of cetuximab simultaneously with the radiotherapy [ 47 , 54 , 55 ]. Retrospectively, however, cetuximab has not been shown to be a comparable alternative to cisplatin with respect to overall and progression-free survival (even taking the propensity score into account [ 56 ]) [ 56 , 57 , 58 ].…”

Cetuximab Resistance in Head and Neck Cancer Is Mediated by EGFR-K521 Polymorphism

“…Head and neck squamous cell carcinomas (HNSCC) are among the most common types of newly diagnosed cancers in men with disappointing outcomes despite intensive treatment (1)(2)(3)(4)(5)(6)(7)(8). Cetuximab, a mAb targeting the extracellular ligand-binding domain of the EGFR, has been shown to prolong overall survival in patients with recurrent or metastatic disease by about three months compared with chemotherapy alone.…”

Simultaneous cytoplasmic and nuclear protein expression of melanoma antigen‐A family and NY‐ESO‐1 cancer‐testis antigens represents an independent marker for poor survival in head and neck cancer

“…1 The prognosis of HNSCC patients with locoregionally advanced tumors is poor as indicated by 5-year overall survival rates of 40-60% in recent clinical trials. [2][3][4][5][6] These results demonstrate the great need for new and more effective therapeutic options.…”

“…Cancers of the oral cavity and pharynx are among the most common types of newly diagnosed cancers in men . The prognosis of HNSCC patients with locoregionally advanced tumors is poor as indicated by 5‐year overall survival rates of 40–60% in recent clinical trials . These results demonstrate the great need for new and more effective therapeutic options.…”