Medical and Pediatric Oncology 19:126-128 (1991)
Phase II Trial of Bisantrene for Metastatic Melanoma: An Illinois Cancer Council Study Patrick J.Stiff, MD, Donald Sweet, MD, Lary J. Kilton, MD, Carole M. Johnson, ART, Betty Muntean, ART, and Richard R. Blough, Ms Sixteen patients with metastatic melanoma entered this phase I1 study of the efficacy of monthly cycles of Bisantrene. Toxicity was characterized by leukopenia, resulting in the hospitalization of one patient for a febrile incident, and superficial
phlebitis. The results were similar to those of previous studies, in that among the 13 patients evaluable for response (six previously untreated with chemotherapy) there were no responses.
Key words: leukopenia, chemotherapy, anthracenedicarboxaldehyde
INTRODUCTION
Bisantrene (anthracenedicarboxaldehyde)is a guanidine-substituted synthetic anthracene derivative with the deletion of the glucosamine side chain [I]. It was found to be active in a number of animal model systems, including B 16 melanoma [2]. In addition, several groups demonstrated some activity of this agent against fresh melanoma cells in the in vitro clonogenic assay system [3,41. Myelosuppression, specifically leukopenia, appears to be the dose-limiting toxicity of Bisantrene. Other reported toxicities include local phlebitis at the infusion site, anaphylaxis after multiple doses, hypotension with rapid infusion, arrhythmias, and fever appearing 2448 hr after treatment [1,5,6]. In a phase I trial of Bisantrene administered weekly, a patient with metastatic melanoma achieved a complete response lasting 6 months [5]. This prompted a phase I1 trial of this agent given weekly, and although there were no responses in that study, two of 16 patients had disease stabilization for 12 and 21 months, respectively [7]. As a result of this accumulated experience, and because of the lack of effective conventional agents for this tumor, we undertook a phase I1 trial of Bisantrene administered every 4 weeks to previously treated and untreated patients. The protocol for this study was approved by the Institutional Review Board of the Illinois Cancer Council and by the human studies review board of each participating institution. MATERIALS AND METHODS
Principal objectives were to see whether Bisantrene alone would produce objective responses in metastatic 0 1991 Wiley-Liss, Inc.
melanoma and to add to existing information about Bisantrene's toxicity. To provide a 95% chance for at least one response, given .15 as hypothetical true response probability, the study design called for 19 patients. However, after 16 patients had been entered, during the years 1982-1985, the study was closed. Patients with histologically proven metastatic melanoma and without possibility of surgical cure were the only candidates for the study. Eligibility requirements included bidimensionally measurable disease or measurable hepatomegaly caused by metastatic disease, performance status 2 or better (Eastern Cooperative Oncology Group [ECOG] scale), absence of acute or chronic infection, serum creatinine
Phase II Trial of Bisantrene for Metastatic Melanoma: An Illinois Cancer Council Study Patrick J.Stiff, MD, Donald Sweet, MD, Lary J. Kilton, MD, Carole M. Johnson, ART, Betty Muntean, ART, and Richard R. Blough, Ms Sixteen patients with metastatic melanoma entered this phase I1 study of the efficacy of monthly cycles of Bisantrene. Toxicity was characterized by leukopenia, resulting in the hospitalization of one patient for a febrile incident, and superficial
phlebitis. The results were similar to those of previous studies, in that among the 13 patients evaluable for response (six previously untreated with chemotherapy) there were no responses.
Key words: leukopenia, chemotherapy, anthracenedicarboxaldehyde
INTRODUCTION
Bisantrene (anthracenedicarboxaldehyde)is a guanidine-substituted synthetic anthracene derivative with the deletion of the glucosamine side chain [I]. It was found to be active in a number of animal model systems, including B 16 melanoma [2]. In addition, several groups demonstrated some activity of this agent against fresh melanoma cells in the in vitro clonogenic assay system [3,41. Myelosuppression, specifically leukopenia, appears to be the dose-limiting toxicity of Bisantrene. Other reported toxicities include local phlebitis at the infusion site, anaphylaxis after multiple doses, hypotension with rapid infusion, arrhythmias, and fever appearing 2448 hr after treatment [1,5,6]. In a phase I trial of Bisantrene administered weekly, a patient with metastatic melanoma achieved a complete response lasting 6 months [5]. This prompted a phase I1 trial of this agent given weekly, and although there were no responses in that study, two of 16 patients had disease stabilization for 12 and 21 months, respectively [7]. As a result of this accumulated experience, and because of the lack of effective conventional agents for this tumor, we undertook a phase I1 trial of Bisantrene administered every 4 weeks to previously treated and untreated patients. The protocol for this study was approved by the Institutional Review Board of the Illinois Cancer Council and by the human studies review board of each participating institution. MATERIALS AND METHODS
Principal objectives were to see whether Bisantrene alone would produce objective responses in metastatic 0 1991 Wiley-Liss, Inc.
melanoma and to add to existing information about Bisantrene's toxicity. To provide a 95% chance for at least one response, given .15 as hypothetical true response probability, the study design called for 19 patients. However, after 16 patients had been entered, during the years 1982-1985, the study was closed. Patients with histologically proven metastatic melanoma and without possibility of surgical cure were the only candidates for the study. Eligibility requirements included bidimensionally measurable disease or measurable hepatomegaly caused by metastatic disease, performance status 2 or better (Eastern Cooperative Oncology Group [ECOG] scale), absence of acute or chronic infection, serum creatinine
