Pharmacokinetics of cisplatin in semi-closed hyperthermic peritoneal perfusion (HPP) for treatment of peritoneal carcinomatosis.

BACKGROUND: This study investigates the pharmacokinetics and toxicity of cisplatin, admininistered by a new semi-closed hyperthermic peritoneal perfusion (HPP) technique to patients with peritoneal carcinomatosis. MATERIALS AND METHODS: After surgical cytoreduction, 12 patients were given cisplatin 100 mg/m2 (CDDP), introduced into the HPP circuit for 60 min at 41.7 degrees C and 1200 ml/min flow rate. Perfusate and blood samples were obtained during/after perfusion, plus normal and tumor tissues samples before/after perfusion. RESULTS: Total and ultrafiltrate (UF) CDDP had similar patterns: monophasic in peritoneum, biphasic in plasma. At the end of perfusion, total/UF platinum (Pt) concentrations in the peritoneum decreased by 63.4%-64.9%. Total/UF Pt concentrations and AUCtot in perfusate were higher than plasmatic ones. Pt concentrations in tumor specimens were higher than in normal tissues. CONCLUSION: Cisplatin administered by semi-closed HPP evidenced pharmacological advantages: higher and direct drug exposure of the tumor within the peritoneal cavity, limited systemic absorption and mild toxicity.

Gemcitabine and oxaliplatin in patients with metastatic breast cancer resistant to or pretreated with both anthracyclines and taxanes: clinical and pharmacokinetic data.

OBJECTIVES: To evaluate the efficacy, the toxicity and the pharmacokinetics of a gemcitabine (GEM) and oxaliplatin (OXA) combination in metastatic breast cancer patients (MBC), previously treated with anthracycline and taxanes. METHODS: A total of 40 women were enrolled; 37 patients had visceral metastases as dominant site of disease, including 20 patients with liver metastases and 14 with multiple visceral metastases. Three patients received neo-adjuvant chemotherapy, 13 patients adjuvant chemotherapy alone, 24 patients chemotherapy for MBC alone. Gemcitabine was given at 1000 mg/m2 on days 1, 8 followed by oxaliplatin at 100 mg/m2 iv on day 2 every 2 weeks (GEM-OXA sequence). Possible pharmacokinetic interactions were studied in 10 patients, by administering on cycle 1 gemcitabine d1/oxaliplatin d2 (GEM-OXA) and on cycle 2 oxaliplatin d1/gemcitabine d2 (OXA-GEM). RESULTS: After a median of 8 cycles, 10 partial response (PR) (25%), 16 stable disease (SD) (40%), and 14 progressive disease (PD) (35%) were obtained. The median duration of response was 6 months (3-9) for responding patients and 4.9 months (2-7.5) for patients with stable disease. For PR, SD and PD patients, median survival was 18 (10-23+), 13 (8-18), and 6 months (4-13), respectively. G3-4 neutropenia occurred in 20% of patients (febrile G3 neutropenia in 2.5%), G3-4 thrombocytopenia and anemia in 15% and 7.5%. The most frequent G3-4 nonhematologic toxicity was represented by peripheral neuropathy (20%), always reversible. The GEM-OXA and OXA-GEM schedules showed a similar pharmacokinetic behavior, with no sequence-dependent interaction. CONCLUSIONS: The combination gemcitabine plus oxaliplatin has moderate activity in anthracycline and taxanes resistant/relapsed heavily treated patients, mild toxicity and no administration sequence-dependent pharmacokinetic interactions.