The rate of failure of
chemotherapy treatment in
ovarian cancer remains high, resulting in a low 5-year survival rate of 20-40% in patients that present with advanced-stage disease. Treatment-free periods between cycles of
chemotherapy may contribute to accelerated
tumor cell proliferation and decreased treatment response. The elimination of treatment-free breaks has been deemed beneficial in the context of cell-cycle-specific agents. The potential benefit of this approach for non-cell-cycle-specific agents has not yet been elucidated. The present study is the first to address this issue by investigating the impact of continuous versus intermittent intraperitoneal administration of
carboplatin over a 14 day period to SCID mice bearing SKOV-3
ovarian cancer xenografts. Immunostaining of
tumor sections was employed to quantify
tumor proliferation, angiogenesis, and apoptosis using Ki-67, CD-31,
caspase-3 (
CASP3), and terminal deoxytransferase-mediated dUTP nick-end labeling (TUNEL). Continuous ip administration of
carboplatin resulted in greater
tumor growth inhibition than intermittent
therapy (p < 0.05). Significantly greater
tumor cell apoptosis and less cell proliferation and angiogenesis were measured in
tumors of mice treated with continuous
carboplatin as compared to both intermittent and control groups. These results indicate that continuous local administration may be a promising approach to improve the effectiveness of
platinum-based
chemotherapy regimens.