TABLE 3

PD parameters estimated from the 22Rv1 and PC3 xenografts PK/PD model

ParameterDefinition22Rv1 Estimate (RSE%) (IIV, CV%)PC3 Estimate (RSE%) (IIV, CV%)
V(0) (mm3)Initial TV (control group)a195 (7) (16.9)145 (3) (2.7)
kng (h−1)Tumor growth rate0.0072 (6) (2.9)0.0025 (9) (21.8)
KP (mm3)Tumor carrying capacity of 22Rv1 model4560 (19) (4)
Nss (mm3)Tumor carrying capacity of PC3 model2090 (16) (30)
kDoc (l ⋅ μg−1 ⋅ h−1)The antitumor effect coefficient of Doc0.000206 (16) (38.9)0.000289 (13) (30.3)
k1 (h−1)Transit-rate constant (Doc monotherapy)b0.0218 (34) (27)0.0179 (16) (26.8)
EC50Cab (μg/l)The concentration of Cab causing half of maximum inhibition on KP (Nss)399 (14) (31.9)2210 (23) (62.1)
φ1φ Value of concurrent schedule0.98 (11) (33.1)1.25 (10) (21.8)
φ2φ Value of interval schedule1.19 (11) (34.4)1.34 (13) (30.8)
φ3φ Value of Doc ∼ Cab sequential schedule2.09 (18) (39.2)3.63 (19) (42.4)
φ4cφ Value of Cab ∼ Doc sequential schedule0.54 (21) (76.9)
σ1 (CV%/S.D.)Residual error of control group9.2/15.9−/34.1
σ2 (CV%/S.D.)Residual error of Doc monotherapy10.7/−5.5/6.9
σ3 (CV%/S.D.)Residual error of Cab monotherapy7.2/−6.1/8.4
σ4 (CV%/S.D.)Residual error of concurrent schedule9.4/163.1/10.8
σ5 (CV%/S.D.)Residual error of interval schedule8.5/10.64.3/18.0
σ6 (CV%/S.D.)Residual error of Doc ∼ Cab10.9/6.4−/21.2
σ7 (CV%/S.D.)Residual error of Cab ∼ Doc5.6/18.3
  • a V0 estimated values (RSE%) in the 22Rv1 model were 212 (9), 230 (8), 178 (7), 196 (6), and 169 (13) for the Doc, Cab, concurrent groups, interval groups, and Doc ∼ Cab sequential group, respectively, and estimated values in the PC3 model were 122 (12), 112 (12), 97.8 (4), 105 (13), 132 (7), and 140 (15) for Doc, Cab, concurrent group, interval group, Doc ∼ Cab, and Cab ∼ Doc sequential group, respectively.

  • b k1 estimated values (RSE%) in the 22Rv1 model were 0.0251 (7), 0.0306 (6), and 0.0183 (12) for the concurrent groups, interval groups, and Doc ∼ Cab sequential group, respectively, and estimated values in the PC3 model were 0.0061 (5), 0.0272 (10), 0, and 0.0271 (21) for the concurrent group, interval group, Doc ∼ Cab, and Cab ∼ Doc sequential groups, respectively.

  • c A subject was removed during the modeling process since its φ approximated to 0.