A Study of Xeloda (Capecitabine) in Combination With Oxaliplatin in Patients With Metastatic Colorectal Cancer.

AUC0-infinity represents the area under the concentration-time curve of the analyte (5'-DFUR) in plasma over the time interval from 0 extrapolated to infinity. The analyte 5'-DFUR, the direct precursor of 5-fluorouracil (5-FU), is considered to be the most important metabolite of capecitabine in plasma. The unit of measure was nanograms per millilitre per hour (ng/mL \* hr).

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post the dose.

Population: All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.

AUC0-infinity represents the area under the concentration-time curve of the analyte (free platinum) in plasma over the time interval from 0 extrapolated to infinity. AUC0-inf for free platinum was calculated for each participant from the concentration-data obtained on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3. Free platinum is not bound to plasma proteins and is considered to be the most clinically significant measure of pharmacological and toxicological activity.

Time frame: Predose , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the 2 hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3.

Population: All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.

AUC0-infinity represents the area under the concentration-time curve of the analyte (total platinum) in plasma over the time interval from 0 extrapolated to infinity.

Time frame: Pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the two hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3

Population: All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.

AUC0-infinity represents the area under the concentration-time curve of the analytes (5'-DFCR, 5-FU, and FBAL) in plasma over the time interval from 0 extrapolated to infinity. After oral administration, capecitabine is first metabolized in the liver to 5'-deoxy-5-fluorocytidine (5'-DFCR), which is then converted to 5'-DFUR, and then catalytically activated to 5-FU.

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post the dose

Population: All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.

Area under the plasma concentration-time curve from time zero to the time of the last measurable plasma concentration time point of capecitabine and its metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL).

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post the dose

Population: All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.

Area under the plasma concentration-time curve from time zero to the time of the last measurable plasma concentration time point of Total And Free Platinum.

Time frame: pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the two hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3.

Population: All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.

CL is a calculation of the rate at which a drug is removed from the body via renal, hepatic and other clearance pathways, expressed as volume (milliliters) per unit of time (hour).

Time frame: Pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the two hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3

Population: All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.

Cmax is defined as maximum observed analyte concentration of Total And Free Platinum.

Time frame: Pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the two hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3.

Population: All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.

t1/2 Beta is the time measured for the plasma concentration to decrease by 1 half to its original concentration of capecitabine and its metabolites (5'-DFUR , 5'-DFCR, 5 FU, and FBAL)

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post the dose

Population: All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.

Number of participants with marked laboratory abnormalities (hematology, coagulation, liver function, renal function, protein, electrolytes, miscellaneous).

Time frame: Up to 28 days after last chemotherapy administration

Population: All 36 participants who received at least one dose of capecitabine.

Cmax is defined as maximum observed analyte concentration of capecitabine and its metabolites (5'-DFUR, 5'-DFCR, 5 FU, and FBAL)

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post the dose

Population: All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.

An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product. This includes any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Pre-existing conditions which worsened during the study were also to be reported as AEs.

Time frame: Approximately 3 Years (up to 28 days after the last intake of study medication)

Population: All 36 participants who received at least one dose of capecitabine.

T1/2 beta is the time measured for the plasma concentration to decrease by 1 half to its original concentration of total and free platinum.

Time frame: Pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours from the beginning of the two hour oxaliplatin infusion on Days 2 to 5 of Cycle 1, and Days 1 to 4 for Cycle 2 and 3

Population: All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.

VSS is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.

Time frame: Pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours

Population: All patients for whom observations contributing to the relevant assessments were available, who did not experience dose reductions, and for whom dosing was as required by the protocol were included in the corresponding analysis.