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.

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: few transient adverse effects; improved Quality of Life; safe; tumor growth reduction.

Figure 1

Study design. Notes: The blue ellipsoids illustrate the strata and open circles indicate randomization. The colored rectangles illustrate the treatment procedure. Abbreviations: BP-C1, benzene-poly-carboxylic acids complex with cis-diammineplatinum (II) dichloride; R, randomization.

Figure 2

The development in sum of the largest diameters of target lesions, in millmeters. Notes: Results are expressed by mean values with 95% confidence intervals illustrated by columns. The green bars show BP-C1, the yellow bars show placebo, and the blue bar shows results after 28 days of follow-up. (A) BP-C1 versus placebo followed by BP-C1 treatment. (B) Extended 64 days of BP-C1 treatment. Abbreviation: BP-C1, benzene-poly-carboxylic acids complex with cis-diammineplatium (II) dichloride.

Figure 3

The development in sum of National Cancer Institute Common Terminology Criteria for Adverse Events score. Notes: Results are expressed by mean values with 95% confidence intervals illustrated by bars. The green bars show BP-C1, the yellow bars show placebo, and the blue bar shows the results after 28 days of follow-up. (A) BP-C1 versus placebo followed by BP-C1 treatment. (B) Extended 64 days of BP-C1 treatment. Abbreviation: BP-C1, benzene-poly-carboxylic acids complex with cis-diammineplatium (II) dichloride.