Article Figures & Data
Figures
- Fig. 1.
Representative patient plasma profile of CPT-11 (•), SN-38 (▾), and SN-38G (♦) after a 90-min i.v. infusion of 320 mg/m2 CPT-11.
- Fig. 2.
Scatterplots of patient CPT-11 (A, n = 34), SN-38 (B, n = 34), and SN-38G (C, n = 34) AUC values versus dose.
- Fig. 3.
Scatterplot of CPT-11 plasma CL versus dose (n = 34).
- Fig. 4.
Scatterplot of SN-38 AUC and neutropenia (percentage change from baseline) for cycle 1 (n = 34).
Tables
- Table 1
Patient characteristics
No. of assessable patients 34 Median age (range) (yrs) 61 (31–80) Sex (M/F) 21/13 ECOG performance status 0 20 1 11 2 3 Tumor type Colorectal 32 Esophageal 1 Gallbladder 1 Prior surgery 33 Prior systemic therapy Chemotherapy (1 regimen/2 regimens) 34 (12/22) Mitomycin C/nitrosourea 2 Immunotherapy 5 Prior radiation therapy 17 AP 14 Other 3 No. of sites of metastases 1 8 2 9 3 or more 17 - Table 2
Dose levels
Dose level (mg/m2) No. of patients with no prior AP radiation No. of patients with prior AP radiation 240 1 2 290 5 7 320 8 5 340 6 0 - Table 3
Hematological toxicity
Dose level (mg/m2) No. of patients Leukopenia Neutropenia Thrombocytopenia 1 2 3 4 1 2 3 4 1 2 3 4 240 3 1 1 0 0 0 1 1 0 2 0 0 0 290 No prior AP RTa 5 1 1 0 1 1 1 0 1 0 0 0 1 Prior AP RT 7 0 1 2 1 0 2 2 1 0 0 0 0 320 No prior AP RT 8 4 1 2 0 2 2 0 2 2 0 0 0 Prior AP RT 5 0 1 3 1 1 1 0 3 1 0 0 0 340 6 0 2 0 1 1 0 0 3 2 1 0 0 -
a RT, radiotherapy.
-
- Table 4
Gastrointestinal toxicity
Dose level (mg/m2) No. of patients Nausea Vomiting Diarrhea Anorexia 1 2 3 1 2 3 4 1 2 3 4 1 2 3 4 240 3 2 1 0 1 0 0 0 2 0 0 0 1 0 0 0 290 No prior AP RTa 5 1 3 1 1 1 0 1 1 1 0 0 1 2 0 0 Prior AP RT 7 4 0 1 0 0 0 1 2 3 0 1 3 2 0 0 320 No prior AP RT 8 3 3 2 2 2 1 1 3 2 1 1 3 2 0 0 Prior AP RT 5 2 1 1 2 0 0 1 4 0 0 1 2 0 1 0 340 6 2 2 0 2 2 0 0 3 1 0 1 2 2 0 0 -
a RT, radiotherapy.
-
- Table 5
Cholinergic symptoms
Symptom NCIa grade % of 34 patients 1 2 3 4 Abdominal pain 6 4 4 0 41.2 Diaphoresis 7 1 0 0 23.5 Diarrhea (early) 3 2 0 1 17.6 Lacrimation 2 0 0 0 5.9 Salivation 1 0 0 0 2.9 -
a NCI, National Cancer Institute.
-
- Table 6
Summary of mean ± SD CPT-11, SN-38, and SN-38G pharmacokinetic parameters
Dose (mg/m2) 240 (n = 3) 290 (n = 12) 320 (n = 13) 340 (n = 6) CPT-11 t1/2 (h) 12.9 ± 3.6 12.8 ± 1.8 11.9 ± 1.7 12.2 ± 1.6 Cmax (ng/ml) 2810 ± 314 3418 ± 975 3432 ± 587 3392 ± 874 AUC (ng/ml·h) 18091 ± 1657 22270 ± 5882 22695 ± 8546 22998 ± 7336 CL (liters/h/m2) 11.6 ± 1.0 12.1 ± 3.8 13.6 ± 4.3 12.1 ± 3.8 Vz (liters/m2) 215 ± 60 229 ± 91 240 ± 95 229 ± 91 Vss (liters/m2) 120 ± 13 122 ± 52 122 ± 35 122 ± 52 SN-38 Tmax (h)a 1.55 ± 0.05 1.84 ± 0.72 2.15 ± 0.83 2.02 ± 0.40 Cmax (ng/ml) 41 ± 2 68 ± 40 68 ± 27 56 ± 28 AUC (ng/ml·h) 638 ± 124 797 ± 405 712 ± 276 714 ± 415 t1/2 (h) 27.1 ± 12.5 21.5 ± 5.7 19.3 ± 7.0 21.0 ± 8.2 SN-38G Tmax (h)a 1.83 ± 0.14 2.07 ± 0.40 2.37 ± 0.61 1.84 ± 0.35 Cmax (ng/ml) 109 ± 30 160 ± 61 198 ± 81 168 ± 69 AUC (ng/ml·h) 1710 ± 465 2421 ± 1347 2663 ± 1413 2329 ± 1199 t1/2z (h) 20.3 ± 3.8 19.7 ± 7.0 17.0 ± 4.5 17.2 ± 3.6 AUC ratiosb SN-38/CPT-11 5.0 ± 0.5 5.2 ± 2.2 4.8 ± 2.1 4.3 ± 1.8 SN-38G/CPT-11 13.7 ± 4.6 15.4 ± 7.2 16.8 ± 8.4 14.1 ± 4.9 -
a Time relative to the start of the infusion.
-
b Ratio of SN-38 or SN-38G to CPT-11 AUC, expressed as a percentage.
-
- Table 7
Spearman correlation between AUC of CPT-11, SN-38, and SN-38G and worst grade toxicity for cycle 1
Toxicity CPT-11 SN-38 SN-38G ρ P ρ P ρ P Nausea 0.19 0.27 0.42 0.01 0.42 0.01 Vomiting 0.37 0.03 0.41 0.02 0.23 0.19 Diarrhea 0.23 0.19 0.33 0.05 0.13 0.45 Neutropenia 0.31 0.07 0.60 0.001 0.13 0.45 Leukopenia 0.27 0.12 0.30 0.09 0.13 0.47 Thrombocytopenia 0.12 0.51 0.31 0.07 0.35 0.04
Volume 6, Issue 6
