Phase I clinical and pharmacokinetic study of mitoxantrone given to patients by intraperitoneal administration.

摘要: Abstract On the basis of its high degree cytotoxicity against fresh human ovarian cancers and relative lack vesicant activity, mitoxantrone administered by i.p. route was studied in a Phase I pharmacokinetic trial. Thirty-three patients with good performance status diagnoses metastatic or recurrent (31 patients) colon (two were treated 12- to 38-mg/m2 doses, every 4 wk for up ten treatment courses. Mitoxantrone doses escalated at 2- 3-mg/m2 increments groups three 11 patients. Thirty-eight mg/m2 (by dwell without removal) considered maximally tolerated dose that, eight patients, four experienced severe leukopenia six abdominal pain. Response evaluable 17 None seven clinically measurable intraabdominal pelvic tumor masses responded; however, (50%) nonmeasurable disease, there normalization previously elevated serum CA-125 concentrations 3, 17, 24 mo. Additionally, two who underwent third-look laparotomies found have >75% reductions response lasting 25 At 38 mg/m2, associated mean concentration time product 100 µg·h/ml space 0.071 plasma, yielding an i.p./plasma area under curve ratio 1408. We conclude that chemical peritonitis is dose-limiting toxicity 23 3 should be used future II trials cancer minimal residual disease following second-look laparotomy.