title: 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: 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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Controlled Clinical Trials and Biostatistics, Centre for Epidemiology and Biostatistics, University of Life Science, Oslo, Norway.
authors.forename: Stig
authors.initials: S
authors.lastname: Larsen
authors.affiliation: Udonthani Cancer Hospital, Udonthani, Thailand.
authors.forename: Kritiya
authors.initials: K
authors.lastname: Butthongkomvong
authors.affiliation: Department of Oncology, City Clinical Oncology, Dispensary, St Petersburg, Russia.
authors.forename: Alexey
authors.initials: A
authors.lastname: Manikhas
authors.affiliation: Department of Oncology, Leningrad Regional Oncology Centre, St Petersburg, Russia.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Trishkina
authors.affiliation: Department of Oncology, Unit of Russian Academy of Medical Science, Moscow, Russia.
authors.forename: Elena
authors.initials: E
authors.lastname: Poddubuskaya
authors.affiliation: Department of Oncology, N Novgorod Regional Oncology Dispensary, Novgorod, Russia.
authors.forename: Marina
authors.initials: M
authors.lastname: Matrosova
authors.affiliation: Division of Medical Oncology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Vichien
authors.initials: V
authors.lastname: Srimuninnimit
authors.affiliation: Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, UK.
authors.forename: Steen
authors.initials: S
authors.lastname: Lindkær-Jensen
keywords: few transient adverse effects; improved Quality of Life; safe; tumor growth reduction