A randomized trial of neoadjuvant vs concomitant chemotherapy vs radiotherapy alone in the treatment of stage IV head and neck squamous cell carcinoma

Abstract

Treatment results of irradiation as a single treatment for advanced stage IV unresectable head and neck cancer remains uniformly poor and apparently has not changed with the most recent improvements in oncological care. Despite several negative results of randomized studies, neoadjuvant or concomitant chemotherapy and radiotherapy seems to improve the number of complete responses and also the duration of disease-free survival. The present study was designed to determine the feasibility, potential risks and benefits of the two methods of combined treatment and radiotherapy alone on the management of advanced unresectable squamous cell carcinoma of the upper respiratory and digestive system. From 1983 to 1986, 90 patients entered the trial. Thirty patients were randomized to each study group: radiotherapy alone (70 Gy); neoadjuvant chemotherapy (vinblastine, mitomycin, cisplatin, and bleomycin) and radiotherapy; concomitant chemotherapy (cisplatin and bleomycin) and radiotherapy. An increased frequency of complete responses (33%) was seen in patients treated with the two different combinations of chemotherapy and irradiation compared to irradiation alone (10%). However, toxicity was more common in patients treated with the two modalities of combined treatment and there were no differences in overall survival rates (P = 0.706).

Oral mucositis in patients undergoing radiation treatment for head and neck carcinoma

“…Virtually all patients who receive radiation therapy for HNC develop some degree of OM. In randomized controlled trials examining the use of conventional versus altered fractionated radiation therapy or combined radiation and chemotherapy, severe OM has been reported in up to 60% of patients receiving standard radiation therapy, and as many as 100% of those receiving either hyperfractionation or accelerated hyperfractionation regimens 2, 11–24. In the current study, the overall incidence of OM was 83%, which is consistent with the estimate of 80% reported by Trotti et al in a recent meta‐analysis of randomized trials of radiation therapy with or without chemotherapy in patients with HNC 2…”

“…Despite its frequency and clinical impact, risk factors for OM in HNC patients have not been well defined to date. The incidence of mucosal injury has been reported to vary with radiation intensity and schedule and chemotherapy agent, dose, and schedule 2, 5–25. Hyperfractionated regimens and the use of conditioning and concomitant chemotherapy in particular increase the risk, severity, and duration of mucosal injury 2, 25.…”

A comparison of radiotherapy or radiochemotherapy with symptomatic treatment alone in patients with advanced head and neck carcinomas

“…We reanalyzed a group of 90 patients included in a prospective randomized trial done at Centro de Tratamento e Pesquisa, Hospital do Câncer A.C. Camargo, São Paulo, Brazil from 1983 to 1986 [5]. The eligibility criteria to be included in the study were: (a) an unresectable lesion; (b) patient's age under 65 years old; (c) no prior treatment; (d) no pulmonary or cardiac disease; (e) histological diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, or hypopharynx; and (f) a Karnofsky's score of 50% or greater.…”

Choosing a concomitant chemotherapy and radiotherapy regimen for squamous cell head and neck cancer: A systematic review of the published literature with subgroup analysis

“…Second, some oncologists may argue that the apparent benefit of concomitant CT observed with nonconventional RT schedules may reflect the relative ineffectiveness of non-conventional fractionation in the control arm. Third, the toxicity experienced with concomitant CT and RT needs Trials of single-agent CT Haselow* 12 Lo 15 Vermund 23 Gupta 25 Fu † 26 Eschwege 27 Browman 38 Jeremic 41a Jeremic 41b Dobrowsky 46 Single-agent trials with conventional RT All trials in 5a except Dobrowsky 46 Combination CT Salvajoli 33 Weissler 34 Merlano 35 to be considered when evaluating the conventional and the altered fractionation RT regimens.…”

“…There are a total of nine trials (10 comparisons) and 1,514 patients involving platinumbased CT. Of the various CT regimens listed, the largest effect is observed for the six trials of combination cisplatin 34,35,42,44,45 or carboplatin 47 plus infusional FU (OR, 0.53; 95% CI, 0.41 to 0.69; p < .00001). The four other platinum-based treatments include two comparisons involving daily, low-dose single-agent cisplatin or carboplatin, both of which were positive, 41 one trial of cisplatin with bleomycin, which was negative, 33 and one trial of low-dose weekly cisplatin, which was negative. 12 A formal statistical test for heterogeneity across the platinum-based CT trials was not significant despite some differences in baseline risk across studies, lending reassurance of the reasonableness of the conclusions.…”