BioMed Research International / 2015 / Article / Tab 3

Review Article

Preclinical Murine Models for Lung Cancer: Clinical Trial Applications

Table 3

Preclinical and clinical trial summaries for lung cancer therapies (CCSP: clara cell secretory protein; rtTA: reverse tetracycline transactivator protein; EGFR: epidermal growth factor receptor; RR: response rate; PFS: progression free survival).

Drug nameRouteMechanismPreclinical dosagePreclinical frequencyFDA approvalPreclinical modelPreclinical resultsClinical DosageClinical FrequencyResults of Clinical TrialsReferences

Gefitinib OralHER1/EGFR inhibitor 0.01 μM 
50–200 mg/kg
qd × 5 days × 2 weeks2009Xenograft-A549 cells in athymic nude Tumor regression and increase in median survival 250 mgqdPositive[66, 67]

ErlotinibOralHER1/EGFR inhibition0.5% (w/v) I.P. or
25 mg/kg/day
qd × 5 days × q4 weeks2005Xenograft-HCC827, A549, NCI358 cells in female BALB/cA nude mice
Transgenic-CCSP-rtTA; Tet-07-EGFRL858R
Tumor regression observed in HCC827 xenografts150 mgqdPositive[26, 49, 68]

VandetanibOralVEGF/EGFR inhibitor25 mg/kgqdNot approvedXenograft-H1975 cells in female athymic nude mice Inhibition of tumor growth (not dramatic) 50–145 mg/m2qd Negative[69]

BIBW2992OralHER2/EGFR inhibitor20 mg/kgqdOctober 2010 Phase III clinical trialXenograft-H1975 cells in female athmyic NMRI-nu/nu mice
Transgenic-CCSP-rtTA; Tet-07-EGFRL858R
Dramatic tumor regression T/C ratio 2%20–70 mgD1, 8, 15 q4 weeksPositive[37, 70]

CrizotinibOralALK inhibitor10 mg/kgqdPhase III clinical trialsTransgenic-SP-C-EML4-ALK in C57BL/6J miceTumor regression and increase in median survival250 mg2 d × 6 monthsPositive[57, 71, 72]

Navelbine (Vinorelbine)Oral,
IV
Antimicrotubule
chemotherapy
1.25–5 mg/kgqd × 9 days1994Immune-C57B1 mice used for transplantation of LLC72.7% inhibition of tumor growth25–30 mg/m2q weeklyPositive[73, 74]

PaclitaxelIVAntimicrotubule
chemotherapy
12–24 mg/kgqd × 5 days1992Xenograft-A549, NCI-H23, NCI-H460, DMS-273, NCI-H226, and DMS-114 cells in nude miceSignificant tumor regression, more effective than cisplatin135 mg/m2q3 weeksPositive[36, 75]

AbraxaneIVAntimicrotubule
chemotherapy
250 mg/kg IPqd × 3 weeksPhase III clinical trials for lung cancerXenograft-H460 cells in female athymic nu/nu miceSignificant tumor regression260 mg/m2q3 weeksPositive[23, 34]

GemcitabineIV Nucleoside analog chemotherapy50–160 mg/kgq3-4 days2006Xenograft-A549 and H1299 cells in female nude mice Reduced mean tumor double time by 50% in 13 days1000 mg/m2D1, 8, 15 q28 daysPositive[32, 76]

Pemetrexed IV Folate antimetabolite chemotherapy30 mg/kgq3-4 days2004Xenograft-H460 cells in female athymic nude Tumor regression duration and dose dependent 500 mg/m2q21 daysPositive[35, 77]

Doxorubicin IV Anthracycline antibiotic chemotherapy3.0–12 mg/kg qd1950’sXenograft-Nu/nu-Balb/c/ABom, normal Balb/c (13)
CB-17 scid/scid with TL-1 s.c. 2 × 10(6) cells in 0.2mL saline (14)
Effective in arresting tumor growth 40–75 g/m2q21–28 daysPositive[41, 78]

Cisplatin IVPlatinum-based chemotherapy7 mg/kg I.Pqd × 2 weeks q4 weeks1969Xenograft-A549, H1299 nude mice
Transgenic-LSLK-RasG12D on 129svJae background
Significantly reduced tumor burden, but left long-term resistance 60 to 100 mg/m2q21 daysPositive[32, 79, 80]

CarboplatinIVPlatinum-based chemotherapy50 mg/kg I.P. qd1989Xenograft-A549 and H1299 cells in athmyic nude mice
Immune-C57B1 mice used for transplantation of LLC
Two-drug regimen response rates 30–50% prolonged median survival of >1 year200–360 mg/m2q4 weeksPositive[32, 40, 81]

EtoposideIV,
oral
DNA topoisomerase II inhibitor1–32 mg/kgqd × 5 days1960’sXenograft-H460 cells in female athmyic nude miceTumor growth regression100 mg/m2 IV
200 mg/m2 PO
q3 weeksPositive[82, 83]

BevacizumabIVMonoclonal antibody VEGF-A inhibitor5 mg/kgqd × 4 weeks2004Xenograft-H1299 cells in athymic BALB/c female nude miceReduced vascularity, reduced interstitial pressure and tumor growth15 mg/kgq3 weeksPositive[84, 85]

Sunitinib oralMultitargeted RTK inhibitor (VEGF, CKit, PDGFα, cRET)40 mg/kgqd × 6 weeksPhase II clinical trials for lung cancerXenograft-NCI-H226, NCI-H526 or NCI-H82 in athmyic female nu/nu miceSignificant tumor growth regression37.5–50 mgcontinuous qd or qd × 4 weeks q6 weeksNegative[42, 86]

SorafiniboralMulti-targeted RTK inhibitor (VEGF, CKit, PDGFα, cRET)40–80 mg/kgqd × 9 daysPhase III clinical trials for lung cancerXenograft-H460, A549, NCI-H23 cells in female NCr-nu/nu miceSignificant tumor growth regression400 mgbidNegative[33, 87]

CetuximabIVMonoclonal antibody EGFR inhibitor20 μL/gq3 weeks2008Xenograft-A549, NCI-H358, HCC-827, H1975, H460 cells in female athmyic nu/nu miceSignificant tumor growth inhibition 250–400 mg/m2400 mg/m2
250 mg/m2 q weekly
Negative[28, 88]

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