A Two-Step Reevaluation of High-Dose Amsacrin for Advanced Carcinoma of the Upper Aerodigestive Tract: A pilot phase II study

Abstract

Results of amsacrine studies in different solid tumors with a dose of 85 mg/m²/24 h × 1 quo 3 weeks have been, in general, disappointing. Although only a few patients with head and neck cancer have been included in broad phase II studies, several responses have been reported, but detailed data concerning responders are lacking. In the present study, amsacrine (Amsidil®, Godecke - Parke Davis) was administered at an increased dose of 85 mg/m²/24 h × 3 (total dose per cycle 255 mg/m²) quo 3 - 4 weeks. 25 patients with advanced carcinoma of meso and hypopharynx were included in the first step of this phase II study (11/25 with histological grades I/II and 14/25 with histological grades III/IV; 10/25 pretreated with radical radiotherapy and 15/25 previously untreated), and 5 patients with undifferentiated carcinoma of the nasopharyngeal type (UCNT), all previously treated. 5/30 patients achieved a complete response (CR) and 5/30 a partial response (PR), the overall response rate being 10/30. Regarding the histology grade, only 1/11 patients with grade I/II carcinoma of meso and hypopharynx achieved a PR with no CR, but 5/14 with grade III/IV from the same group achieved a CR. Out of 10 pretreated patients only one achieved any response and none of the 5 patients with UCNT. Thus, in the second step of this study, high dose amsacrine was evaluated in the target group of previously untreated patients with advanced grade III/IV carcinoma of meso and hypopharynx. 20 patients were included in the second step and all were evaluable for activity. A CR was achieved for 6/20 patients and a PR for 7/20 patients (response rate 65%, 95% confidence interval 44%-86%). Hematological toxicity from both steps included grade IV granulocytopenia in 25/50 patients (50%, 95% confidence interval 36%-64%) and grade IV thrombocytopenia in 18/50 patients (36%, 95% confidence interval 23%-49%). High dose amsacrine seems to be a toxic, but very effective drug as first-line treatment for poorly differentiated carcinoma of meso and hypopharynx, and further studies seem warranted.