Combined chemotherapy and radiation therapy in advanced inoperable squamous cell carcinoma of the head and neck. The final report of a randomized trial

Abstract

Between 1983 and 1986, the National Institute for Cancer Research in Genoa and affiliated institutions conducted a randomized study to compare two different ways of combining chemotherapy (CT) and radiation therapy (RT). One hundred sixteen patients were randomized to receive neoadjuvant CT followed by definitive RT (treatment arm A) or alternating CT and RT. In treatment arm A, RT consisted of 70 Gy to the involved areas and 50 Gy to the uninvolved neck at 2 Gy/fraction, five fractions per week. In treatment arm B, RT consisted of 60 Gy to involved areas and 50 Gy to the uninvolved neck in three courses of 20 Gy each, 2 Gy/fraction, ten fractions/2 weeks alternated with four courses of CT. CT consisted of vinblastine 6 mg/m2 intravenously followed 6 hours later by bleomycin 30 IU intramuscularly, day 1; methotrexate 200 mg intravenously, day 2; leucovorin rescue, day 3. CT was repeated every 2 weeks up to four courses. The same CT was used in both treatment arms of the study. Fifty-five patients were entered in treatment arm A and 61 in treatment arm B. Complete responses were 7/48 and 19/57 in treatment arms A and B, respectively (P less than 0.03). Four-year progression-free survival was 4% in treatment arm A and 12% in treatment arm B (P less than 0.02), and four-year survival was 10% in A and 22% in B (P less than 0.02). Mucosal tolerance was significantly worse in treatment arm B (P less than 0.00004). The subgroup analysis shows the major improvement of alternating CT and RT in patients with the worst prognostic characteristics.

Oral complications in patients receiving head and neck radiation therapy: a literature review

“…Approximately 60% of the patients receive radiation therapy to treat head and neck cancer and most receive the combined therapy so that the development of a series of changes is expected to affect the oral cavity 5 .…”

Phase II Trial of Hyperfractionated Accelerated Split-Course Radiochemotherapy with 5-FU and Cis-DDP in Advanced Head and Neck Cancer

“…Induction chemotherapy was despite high remission rates not able to improve overall survival [2,3,8,24,31,38,40]. A significant improvement of local tumor control has been shown for concurrent 5-FU, CDDP, carboplatin, mitomycin C and methotrexate and radiotherapy [3,31,45,47].…”

Altered fractionation in the treatment of head and neck cancer

“…Merlano et al [40,41] reported a second trial comparing the alternating regimen with that of neoadjuvant chemotherapy followed by definitive radiation for unresectable head and neck cancer (Table 3). Patients were randomized to alternating chemoradiotherapy delivering 60 Gy of split-course radiation as described above with vinblastine, bleomycin, methotrexate, and leucovorin (VBM) instead of 5-FU/CDDP versus induction chemotherapy with all four courses of VBM given upfront followed by conventionally fractionated radiotherapy to 70 Gy in 2-Gy daily fractions [40,41].…”