Benzene-Poly-Carboxylic Acids Complex with Cis-Diammineplatinum (II) Dichloride in the Treatment of Stage IV Breast Cancer Patients

ABSTRACT

An anti-cancer agent containing benzene-poly-carboxylic acids complex with cis-diammineplatinum (II) dichloride (BP-C1) was developed to establish a low toxic and cost effective treatment of breast cancer. The study was aimed to investigate if BP-C1 could be given continuously without rest periods and to estimate Maximum Tolerated (MTD) and Minimum Efficient Dose (MED) in metastatic breast cancer (MBC) treatment. A non-randomized, multicentre trial with 3-level Response Surface Pathway design was performed. Five MBC patients were included at each of the three design levels. BP-C1 was daily administrated intramuscularly during 32 days. The first five patients were given a cumulative dose of 0.64 mg/kg bodyweight. Based on the obtained results, the dose was increased /decreased for the next five patients in the next design level. The main variable was the National Cancer Institute Common Toxicity Criteria (NCI-CTC). Cumulative doses of 0.96 mg/kg or higher were defined as high-dose. One moderate and one mild increase in maximum NCI-CTC were found on 0.64 mg/kg, one mild increase occurred on 0.96 mg/kg and no changes were detected on 1.12 mg/kg. The Sum NCI-CTC increased (p=0.07) in the low-dose group, but reduced (p=0.09) in the high-dose group. In the high-dose group, 62.5% of the patients were classified as responders including one complete responder compared to 28.6% in the low-dose group. In conclusion, BP-C1 can safely be administrated continuously during 32 days. The MTD is larger than 1.12 mg/kg and MED estimated to 0.96 mg/kg.

Keywords:

Benzene-poly-carboxylic acids complex with cis-diammineplatinum (II) dichloride, dose-response, response surface pathway design.