A phase I and pharmacokinetic study of intraperitoneal carboplatin and etoposide.
BACKGROUND
We attempted to determine the maximum tolerated dose and toxicity of etoposide (VP-16) when administered in combination with carboplatin (CBDCA) (300 mg m-2) and administered via the intraperitoneal (IP) route.


METHODS
A total of 26 patients were treated on this trial. CBDCA was administered at a fixed dose of 300 mg m-2) while VP-16 was started at a dose of 200 mg m-2 and escalated at 50 mg m-2 increments. Both agents were mixed together in 2 litres of 5% Dextrose and administered as quickly as possible into the peritoneal cavity. Pharmacokinetic studies were performed at the maximum tolerated dose (MTD).


RESULTS
The MTD for this regimen was CBDCA 300 mg m-2 and VP-16 350 mg m-2. Patients > or = 70 years of age or who had received more than six cycles of previous chemotherapy, tolerated this regimen poorly. The MTD for this group of patients was CBDCA 200 mg m-2 and VP-16 50 mg m-2. Neutropenia was the dose limiting toxicity for both groups. The mean peritoneal/plasma peak ratio was 18.3 for CBDCA and 12.7 for VP-16. The pharmacologic advantage (peritoneal/plasma AUC ratio) was 14.9 for CBDCA and 8.8 for VP-16. Although measurable disease was not a requirement for entrance into this study a response rate of 27% was noted in 15 patients with evaluable disease who had ovarian cancer.


CONCLUSIONS
A pharmacologic advantage exists for both CBDCA and VP-16 when administered together via the IP route.
Department of Medicine, University of California, San Diego 92103.
E F
EF
McClay
R
R
Goel
P
P
Andrews
S
S
Gorelick
S
S
Kirmani
S
S
Kim
P
P
Braly
S
S
Plaxe
S
S
Hoff
J
J
Alcaraz
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009503:Neutropenia / Q000139:chemically induced; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism
D005047:Etoposide; D016190:Carboplatin