Table 4.
Association between pharmacokinetic parameters and vincristine induced peripheral neuropathy, additionally corrected for age, sex, VCR dose per m2, disease, concurrent azole-antifungal treatment, and self-declared ancestry.
| Total CTCAE Score | Total Ped-mTNS Score | VIPN CTCAE Score No/Yes * | VIPN Ped-mTNS Score No/Yes * | |||||
|---|---|---|---|---|---|---|---|---|
| Beta (95% CI) | p Value | Beta (95% CI) | p Value | OR (95% CI) | p-Value | OR (95% CI) | p-Value | |
| Cl(L/hr/m2) | 0.00 (−0.04 to 0.05) | 0.90 | 0.02 (−0.09 to 0.14) | 0.70 | 1.01 (0.96–1.06) | 0.74 | 1.05 (0.99–1.12) | 0.11 |
| V1 (L/m2) | −0.00 (−0.06 to 0.09) | 0.96 | −0.03 (−0.19 to 0.13) | 0.72 | 1.00 (0.89–1.11) | 0.93 | 0.98 (0.91–1.07) | 0.98 |
| IC-Cl (L/h/m2) | 0.01 (0.00–0.02) | 0.04 | 0.04 (0.01–0.07) | 0.004 | 1.02 (1.00–1.03) | 0.02 | 1.05 (1.02–1.09) | 0.001 |
| V2 (L/m2) | −0.00 (−0.00 to 0.00) | 0.88 | 0.01 (−0.00 to 0.02) | 0.20 | 1.00 (0.99–1.00) | 0.29 | 1.00 (1.00–1.01) | 0.81 |
| Plasma AUC (ng·h/mL) | −0.01 (−0.06 to 0.03) | 0.54 | −0.06 (−0.16 to 0.05) | 0.27 | 0.97 (0.93–1.02) | 0.21 | 0.95 (0.89–1.02) | 0.18 |
| Peripheral AUC (ng·h/mL) | −0.01 (−0.05 to 0.04) | 0.76 | −0.05 (−0.16 to 0.06) | 0.34 | 0.98 (0.93–1.03) | 0.40 | 0.97 (0.91–1.04) | 0.41 |
| Plasma Cmax (ng/mL) | −0.01 (−0.03 to 0.02) | 0.55 | 0.00 (−0.08 to 0.07) | 0.94 | 0.96 (0.92–1.00) | 0.05 | 0.99 (0.96–1.02) | 0.53 |
| Peripheral Cmax (ng/mL) | −0.00 (−0.36 to 0.35) | 0.99 | −0.31 (−1.27 to 0.65) | 0.52 | 0.97 (0.64–1.47) | 0.89 | 0.96 (0.61–1.49) | 0.85 |
Common toxicity criteria of adverse event (CTCAE); pediatric-modified total neuropathy score (ped-mTNS); vincristine induced peripheral neuropathy (VIPN); clearance (Cl); confidence interval (CI); volume of distribution of the central compartment (V1); intercompartmental clearance (IC-Cl); volume of distribution of the peripheral compartment (V2); area under the concentration time curve (AUC);, maximum concentration (Cmax). * No VIPN as reference.