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 x 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 x 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.

Head and neck cancer: a step forward

“…For instance, authors dealing with undiff erentiated carcinoma of the nasopharynx in non-endemic areas tend to use the classical 5-FU-CDDP regimen [23], whilst those dealing with the disease in endemic regions apparently prefer anthracyclinebased regimens, prefering epirubicin or zorubicin to doxorubicin [24,25]. Some small studies would indicate that orphan drugs, such as amsacrine might be appropriate for some histologies [26].…”

Amsacrine and Cisplatin in Poor Prognosis Patients with Metastatic Transitional Cell Carcinoma of the Urothelium: A Phase–II Study

“…Several studies have evaluated higher amsacrine dosages in solid tumors with promising results [10, 11], but nevertheless the topic of amsacrine efficacy investigations in solid tumors was regarded as a dead issue [12]. There has been renewed interest in amsacrine efficacy for urothelial [8, 13]and head and neck cancer [14], but in the last decade data concerning amsacrine activity in solid tumors are lacking.…”

Design Synthesis of Novel Acridine Tagged Pyrazole Derivatives as Aurora Kinase Inhibitors

“…Accordingly, this acridine has been clinically utilized as a single agent or in combination with other anti-neoplastic drugs in the treatment of acute nonlymphocytic, lymphocytic [6,7] and acute myeloid [8], leukemias [9]. However, m-Amsacrine has not generally been effective in the treatment of solid tumors [10]. Acridine has an irritating odor.…”