BBR 3438, a novel 9-aza-anthrapyrazole, in patients with advanced gastric cancer: a phase II study group trial of the Central European Society of Anticancer-Drug Research (CESAR).

ABSTRACT

BBR 3438, a member of the 9-aza-anthrapyrazole family designed to decrease anthracycline dependent cardiotoxicity and to improve efficacy provided high in vivo activity in gastric carcinoma xenograft models. The present study was carried out to assess the efficacy and safety of BBR 3438 applied at a dose of 50 mg/m(2) four-weekly as an 1-hour infusion to pretreated patients with gastric cancer. Twenty-seven patients received at least one administration of BBR 3438. Lymph nodes and liver were the most common sites of metastases. A total of 94 cycles were administered (median 2, range 1-6). The main toxicity consisted of (worst per patient [%]; NCIC CTC grades 1/2/3/4) neutropenia 7/7/19/52 (one case of febrile neutropenia), stomatitis 15/19/4/-, nausea 22/26/7/-, vomiting 19/7/7/-, alopecia 15/33/-/-. Neutrophil nadir (520/mul) was reached after a median 15 days. The median time to recovery to < or = grade 1 neutropenia was 13.5 days. The median average cumulative dose of BBR 3438 was 166.8 mg, and the median dose intensity was 48.8 mg/m(2). Left ventricular ejection function (LVEF) was monitored with multiple-gated angiography (MUGA). Median LVEF values at baseline and at the end of cycle 2 were 67.5% and 65%, respectively, and no patient showed a relevant decrease of LVEF. In 25 patients evaluable for response no remission was observed. Four patients (16%) had stable disease. Median time to progression was 51 days, median overall survival was 64 days. In all, the feasibility and tolerability of BBR 3438 applied 4-weekly at a dose of 50 mg/m(2) was confirmed and neither relevant LVEF decreases nor hints of cardiac toxicity were observed. In terms of antitumor activity, BBR 3438 was found to be ineffective in the treatment of gastric cancer.