Satraplatin, an oral platinum, administered on a five-day every-five-week schedule: a pharmacokinetic and food effect study.
OBJECTIVE
The study aimed to assess the pharmacokinetic behavior of satraplatin under fasted and fed conditions, and its safety and preliminary antitumor activity in adults with advanced solid tumors.


METHODS
Satraplatin was administered orally at 80 mg/m(2) once daily with prophylactic antiemetics for 5 consecutive days every 5 weeks. Patients were randomized to receive day 1 and day 5 doses of satraplatin in either the fed or fasted state, the order being reversed for cycle 2. Pharmacokinetic sampling was done during the first two cycles. For all subsequent cycles, patients received satraplatin in the fasted state.


RESULTS
Seventeen patients were treated with 60 total cycles of satraplatin. There was no dose-limiting toxicity during cycle 1. Severe hematologic toxicity was rare and the hematologic nadir occurred during week 4. Nausea, vomiting, and diarrhea were grade 1/2. No significant cardiac, renal, hepatic, or neurologic toxicity was observed. The hypothesis that food decreased ultrafiltrate platinum bioavailability could not be rejected, as the lower limit of the 90% confidence intervals for peak plasma concentration and area under the concentration-time curve from time 0 to 24 hours were 56.14% and 73.53%, respectively, both below the 80% bioequivalence acceptance criterion. One partial response (hormone refractory prostate cancer) and four durable stable diseases (breast, ovarian, parotid, and hormone refractory prostate cancer) were confirmed.


CONCLUSIONS
There is an effect of food on the pharmacokinetics of satraplatin, the clinical significance of which is unclear. It is recommended that satraplatin be administered in the fasting state. This 5-week interval schedule of satraplatin was well tolerated in heavily pretreated patients.
Ricart
Alejandro D
AD
Institute for Drug Development, Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Sarantopoulos
John
J
Calvo
Emiliano
E
Chu
Quincy S
QS
Greene
Douglas
D
Nathan
Faith E
FE
Petrone
Michael E
ME
Tolcher
Anthony W
AW
Papadopoulos
Kyriakos P
KP
D015746:Abdominal Pain / Q000139:chemically induced; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D004435:Eating; D005215:Fasting; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D014839:Vomiting / Q000139:chemically induced
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C081294:satraplatin