The disposition of intraperitoneal bleomycin, melphalan, and vinblastine in cancer patients

We have studied the disposition of bleomycin, melphalan, or vinblastine after intraperitoneal (IP) instillation in 14 cancer patients. Although IP bleomycin had a somewhat longer terminal-phase plasma half-life than after intravenous (IV) administration (5.5 vs 4.0 h, respectively), its systemic absorption averaged only 44%-52% of the administered dose. IP melphalan's mean terminal-phase half-life of 1.3 h was similar to that seen after IV drug administration. Melphalan's systemic absorption form the IP space averaged only 39% of the administered dose. In contrast, vinblastine plasma levels remained elevated for longer than 24 h after IP instillation. Its use was associated with life-threatening adynamic ileus in two patients. Bleomycin's and melphalan's reduced systemic availability after IP dosing suggests that their dose could be increased safely by a factor of two over their standard IV doses.