Premium
Intraperitoneal Topoisomerase‐I Inhibitors: Preliminary Findings with 9‐Aminocamptothecin
Author(s) -
MUGGIA FRANCO,
LIEBES LEONARD,
POTMESIL MILAN,
HAMILTON ANNE,
HOCHSTER HOWARD,
HORNREICH GILA,
SORICH JOAN,
DOWNEY ANDREA,
WASSERSTROM HEATHER
Publication year - 2000
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2000.tb07036.x
Subject(s) - regimen , medicine , topoisomerase , camptothecin , neutropenia , etoposide , pharmacology , area under the curve , gastroenterology , chemotherapy , chemistry , in vitro , biochemistry , organic chemistry
A bstract : The i.p. administration of topoisomerase I (Topo I) inhibitors has a pharmacologic advantage over intravenous application, including preservation of the biologically active lactone form. In our ongoing study, patients have received 9‐amino‐20(S)‐camptothecin (9‐AC) i.p. on days 1, 3, 5, 8, 10, and 12, repeated every 4 weeks. The daily dose has been escalated to level IV of 1.5 mg/m 2 (9.0 mg/m 2 per course), median of 3 cycles, range 1–4, with a reversible Grade 3 neutropenia in one patient. Responses included one CR (resolution of a pleural effusion), two patients without progressive disease (PD), two not evaluable, and two patients too early for evaluation. The area under the curve (AUC)ip/AUCpl ratio (pharmacologic advantage) ranged from 7.6 to 16.5 on average, and, using nonlinear modeling, the pharmacologic decay data were fit to one‐ or two‐compartmental models. Overall, a 9‐AC i.p. application is well tolerated and anticipated to be an active regimen against i.p. malignancies, particularly those known to be sensitive to systemic Topo‐I inhibitors.