Abstract
Purpose: 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. Experimental Design: Satraplatin was administered orally at 80 mg/m2 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3866-3871 |
| Number of pages | 6 |
| Journal | Clinical Cancer Research |
| Volume | 15 |
| Issue number | 11 |
| DOIs | |
| State | Published - Jun 1 2009 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Satraplatin, an oral platinum, administered on a five-day every-five-week schedule : A pharmacokinetic and food effect study. / Ricart, Alejandro D.; Sarantopoulos, John; Calvo, Emiliano; Chu, Quincy S.; Greene, Douglas; Nathan, Faith E.; Petrone, Michael E.; Tolcher, Anthony W.; Papadopoulos, Kyriakos P.
In: Clinical Cancer Research, Vol. 15, No. 11, 01.06.2009, p. 3866-3871.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Satraplatin, an oral platinum, administered on a five-day every-five-week schedule
T2 - A pharmacokinetic and food effect study
AU - Ricart, Alejandro D.
AU - Sarantopoulos, John
AU - Calvo, Emiliano
AU - Chu, Quincy S.
AU - Greene, Douglas
AU - Nathan, Faith E.
AU - Petrone, Michael E.
AU - Tolcher, Anthony W.
AU - Papadopoulos, Kyriakos P.
PY - 2009/6/1
Y1 - 2009/6/1
N2 - Purpose: 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. Experimental Design: Satraplatin was administered orally at 80 mg/m2 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.
AB - Purpose: 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. Experimental Design: Satraplatin was administered orally at 80 mg/m2 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.
UR - http://www.scopus.com/inward/record.url?scp=66649115071&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=66649115071&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-08-2373
DO - 10.1158/1078-0432.CCR-08-2373
M3 - Article
C2 - 19458055
AN - SCOPUS:66649115071
VL - 15
SP - 3866
EP - 3871
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 11
ER -