Satraplatin, an oral platinum, administered on a five-day every-five-week schedule: A pharmacokinetic and food effect study

Alejandro D. Ricart, John Sarantopoulos, Emiliano Calvo, Quincy S. Chu, Douglas Greene, Faith E. Nathan, Michael E. Petrone, Anthony W. Tolcher, Kyriakos P. Papadopoulos

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)3866-3871
Number of pages6
JournalClinical Cancer Research
Volume15
Issue number11
DOIs
StatePublished - Jun 1 2009

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Platinum
Appointments and Schedules
Pharmacokinetics
Food
Prostatic Neoplasms
Ovarian Diseases
Hormones
Therapeutic Equivalency
Breast Diseases
Antiemetics
satraplatin
Nausea
Nervous System
Biological Availability
Vomiting
Diarrhea
Fasting
Research Design
Confidence Intervals
Kidney

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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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 journalArticle

Ricart, AD, Sarantopoulos, J, Calvo, E, Chu, QS, Greene, D, Nathan, FE, Petrone, ME, Tolcher, AW & Papadopoulos, KP 2009, 'Satraplatin, an oral platinum, administered on a five-day every-five-week schedule: A pharmacokinetic and food effect study', Clinical Cancer Research, vol. 15, no. 11, pp. 3866-3871. https://doi.org/10.1158/1078-0432.CCR-08-2373
Ricart, Alejandro D. ; Sarantopoulos, John ; Calvo, Emiliano ; Chu, Quincy S. ; Greene, Douglas ; Nathan, Faith E. ; Petrone, Michael E. ; Tolcher, Anthony W. ; Papadopoulos, Kyriakos P. / Satraplatin, an oral platinum, administered on a five-day every-five-week schedule : A pharmacokinetic and food effect study. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 11. pp. 3866-3871.
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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.

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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.

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