Phase I trial of radiochemotherapy with bendamustine in patients with recurrent squamous cell carcinoma of the head and neck

Background and Purpose: After initial radiochemotherapy of head-and-neck cancers, therapeutic options are often limited for patients with progressive disease. Reirradiation, with or without chemotherapy, appears to be the most potential treatment option. The aim of this study was to determine the maximum tolerated dose of bendamustine in combination with reirradiation for these patients. Patients and Methods: 13 patients with recurrent squamous cell carcinoma of the head-and-neck region after initial radiochemotherapy were treated. Reirradiation of the recurrent region under protection of the spinal cord consisted of 1.8 Gy given five times per week, up to 30.6 Gy. Simultaneous bendamustine was administered on days 1 and 2 at increasing dose levels (80, 100, and 120 mg/m(2) bendamustine). The regimen was administered every 4 weeks. A minimum of three patients were enrolled at each dose level. Results: The therapy was well tolerated. Patients received one to six cycles of bendamustine (median: three). Hematologic toxicities observed were leukocytopenia, thrombocytopenia, or anemia. At dose level II (100 mg/m(2) bendamustine), grade 3/4 hematologic toxicity was seen in one patient so that this level was filled up to six patients. There was no grade 3/4 toxicity seen in the other twelve patients. The most frequent nonhematologic toxicities (grade 1 or 2) were infections (in most cases C-reactive protein elevations without other clinical signs of infection) and nausea. Conclusion:The reapplication of radiochemotherapy with bendamustine is well tolerated. The recommended dose for phase II studies was established at dose level III (bendamustine 120 mg/m(2)).