BP-C1 in the treatment of patients with stage IV breast cancer: a randomized, double-blind, placebo-controlled multicenter study and an additional open-label treatment phase

Abstract

Stig Larsen,1 Kritiya Butthongkomvong,2 Alexey Manikhas,3 Ekaterina Trishkina,4 Elena Poddubuskaya,5 Marina Matrosova,6 Vichien Srimuninnimit,7 Steen Lindkær-Jensen81Department of Controlled Clinical Trials and Biostatistics, Centre for Epidemiology and Biostatistics, University of Life Science, Oslo, Norway; 2Udonthani Cancer Hospital, Udonthani, Thailand; 3Department of Oncology, City Clinical Oncology, Dispensary, St Petersburg, Russia; 4Department of Oncology, Leningrad Regional Oncology Centre, St Petersburg, Russia; 5Department of Oncology, Unit of Russian Academy of Medical Science, Moscow, Russia; 6Department of Oncology, N Novgorod Regional Oncology Dispensary, Novgorod, Russia; 7Division of Medical Oncology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; 8Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, UKAbstract: The aims were to compare the efficacy and tolerability of a new benzene-poly-carboxylic acids complex with cis-diammineplatinum (II) dichloride (BP-C1) versus placebo and to investigate the long-term tolerability of BP-C1 in the treatment of patients with metastatic breast cancer.Material and methods: A randomized, double-blind, placebo-controlled multicenter study was performed with a semi-crossover design. Patients allocated to placebo switched to BP-C1 after 32 days of treatment. Patients who completed 32 days of BP-C1 treatment were offered the opportunity to continue on BP-C1 for an additional 32 days in an open-label extension. Patients were then followed up for another 28 days. Thirty patients were given daily intramuscular injections of 0.035 mg/kg of body weight BP-C1 or placebo for 32 days. Biochemistry, hematology, National Cancer Institute Common Terminology Criteria for Adverse Events (CTC-NCI), European Organisation for Research and Treatment of Cancer quality of life questionnaire (QOL-C30 and the breast-cancer–specific BR23) data were recorded at screening and after every 16 days of treatment. Computed tomography was performed at screening and every 32 days.Results: The sum of target lesions increased 2.4% in the BP-C1 group and 14.3% in the placebo group. Only the increase in the placebo group was significant (P=0.013). The difference between the groups was significant in favor of BP-C1 (P=0.04). There was a significant difference (P=0.026) in favor of BP-C1 regarding Response Evaluation Criteria In Solid Tumors (RECIST) classification. The sum of lesions increased slightly in the patients receiving 64 days of continuous BP-C1 treatment, of whom 68.4% were classified as responders. The sum CTC-NCI toxicity score increased nonsignificantly in the BP-C1 group but significantly in the placebo group (P=0.05). The difference in increase between groups did not meet the level of significance (P=0.12). The sum toxicity score was reduced in the patients receiving 64 days of BP-C1 from 9.2 at screening to 8.9 at Day 48, but it increased again to 10.1 by Day 64 and 10.6 during the 28-day follow-up. "Breast cancer-related pain and discomfort" and "Breast cancer treatment problem last week" were significantly reduced (P=0.02) in the BP-C1 group but increased slightly in the placebo group; between-group differences were significant in favor of BP-C1 (P=0.05). "Breast cancer related pain and discomfort", "Breast cancer treatment problem last week," and "Physical activity problem" were significantly reduced during the 64 days of BP-C1 treatment (P≤0.05).Conclusion: For patients suffering from stage IV metastatic breast cancer, treatment with BP-C1 reduces cancer growth, is well tolerated, improves quality of life, and produces few adverse events, which were mainly mild and manageable.Keywords: tumor growth reduction, improved Quality of Life, safe, few transient adverse effects