Daily oral OSI-906 reduced growth of NCI-H187, LX33 and LX36 SCLC xenografts compared with vehicle. Tumors continued to progress during treatment, limiting the interpretation to partial growth inhibition in these models. [1]
After a single oral OSI-906 dose, tumor 18FDG uptake decreased in NCI-H292 xenografts at 2, 4 and 24 hours, while NCI-H441 xenografts showed no significant change. This demonstrates a model-dependent pharmacodynamic response. [2]
Partial growth inhibition in three SCLC xenograft models
Animal study · NCI-H187, LX33 and LX36 xenografts in female Nu/Nu mice. [1]
Daily oral OSI-906 inhibited tumor growth compared with vehicle in all three SCLC models, with continued progression during treatment.
Conditions shared by the study groups
- Route
- Oral (PO)
- Frequency
- Daily
- Treatment course
- 17–21 days across the three models
- Vehicle
- 25 mM tartaric acid
- H187 xenograft
- Model: Female Nu/Nu mice, 6–8 weeks old, bearing NCI-H187 cell-line xenografts.
- Reported limits: Exact per-model assigned sample size is not tabulated; caption gives cohorts of 6–7 per treatment arm.
- LX33 xenograft
- Model: Female Nu/Nu mice, 6–8 weeks old, bearing LX33 patient-derived SCLC xenografts.
- Reported limits: Exact per-model assigned sample size is not tabulated; caption gives cohorts of 6–7 per treatment arm.
- LX36 xenograft
- Model: Female Nu/Nu mice, 6–8 weeks old, bearing LX36 patient-derived SCLC xenografts.
- Reported limits: Exact per-model assigned sample size is not tabulated; caption gives cohorts of 6–7 per treatment arm.
Methods and source locations
Compound reported in the paper: Linsitinib (OSI-906); Compound label in the paper: OSI-906
Results concern the paper-tested OSI-906 material; they do not validate an Adooq lot or an unspecified stereoisomer.
Figure 6A–C and caption; Materials and Methods, In vivo studies (S10); Results, final two paragraphs.
Longitudinal xenograft tumor volume: Caliper measurements every three days; group means with SEM; mixed effects linear model of log tumor size over time. — Figure 6A–C and caption; Materials and Methods, In vivo studies (S10); Results, final two paragraphs.
H187 xenograft · Figure 6A–C and caption; Materials and Methods, In vivo studies (S10); Results, final two paragraphs.
LX33 xenograft · Figure 6A–C and caption; Materials and Methods, In vivo studies (S10); Results, final two paragraphs.
LX36 xenograft · Figure 6A–C and caption; Materials and Methods, In vivo studies (S10); Results, final two paragraphs.
Model-dependent tumor glucose-tracer response after one dose
Animal study · NCI-H292 and NCI-H441 xenografts in female athymic nude mice. [2]
One oral dose reduced tumor 18FDG uptake in NCI-H292 but produced no significant uptake change in NCI-H441.
Conditions shared by the study groups
- Route
- Oral gavage
- Frequency
- Single dose
- Treatment course
- PET assessed at 2, 4 and 24 h after dosing; vehicle assessed at 4 h
- Vehicle
- 25 mM tartaric acid
- NCI-H292 tumor PET
- Model: NCI-H292 xenografts in female athymic nude mice, 5–6 weeks old.
- Reported limits: Methods state n = 8/group; the NCI-H292 vehicle plot contains more observations than eight and pooling is not explained. No exact plotted sample count is inferred.
- NCI-H441 tumor PET
- Model: NCI-H441 xenografts in female athymic nude mice, 5–6 weeks old.
- Reported limits: Methods state n = 8/group; the NCI-H292 vehicle plot contains more observations than eight and pooling is not explained. No exact plotted sample count is inferred.
Methods and source locations
Compound reported in the paper: Linsitinib (OSI-906); Compound label in the paper: OSI-906
Results concern the paper-tested OSI-906 material; they do not validate an Adooq lot or an unspecified stereoisomer.
Figure 4A–C and caption; Methods, Mouse Models (S9), 18FDG-PET Imaging (S11), Statistical Analysis of Data (S12); Results, Inhibition of 18FDG uptake in vivo.
Tumor 18FDG uptake: Tumor regions of interest on static PET images; Wilcoxon rank-sum comparisons against vehicle, without multiplicity adjustment. No exact %ID/g value is read from plotted points. — Figure 4A–C and caption; Methods, Mouse Models (S9), 18FDG-PET Imaging (S11), Statistical Analysis of Data (S12); Results, Inhibition of 18FDG uptake in vivo.
NCI-H292 tumor PET · Figure 4A–C and caption; Methods, Mouse Models (S9), 18FDG-PET Imaging (S11), Statistical Analysis of Data (S12); Results, Inhibition of 18FDG uptake in vivo.
NCI-H441 tumor PET · Figure 4A–C and caption; Methods, Mouse Models (S9), 18FDG-PET Imaging (S11), Statistical Analysis of Data (S12); Results, Inhibition of 18FDG uptake in vivo.
