Table 3.
Drug name | Route | Mechanism | Preclinical dosage | Preclinical frequency | FDA approval | Preclinical model | Preclinical results | Clinical Dosage | Clinical Frequency | Results of Clinical Trials | References |
---|---|---|---|---|---|---|---|---|---|---|---|
Gefitinib | Oral | HER1/EGFR inhibitor |
0.01 μM 50–200 mg/kg |
qd × 5 days × 2 weeks | 2009 | Xenograft-A549 cells in athymic nude | Tumor regression and increase in median survival | 250 mg | qd | Positive | [66, 67] |
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Erlotinib | Oral | HER1/EGFR inhibition | 0.5% (w/v) I.P. or 25 mg/kg/day |
qd × 5 days × q4 weeks | 2005 |
Xenograft-HCC827, A549, NCI358 cells in female BALB/cA nude mice Transgenic-CCSP-rtTA; Tet-07-EGFRL858R |
Tumor regression observed in HCC827 xenografts | 150 mg | qd | Positive | [26, 49, 68] |
| |||||||||||
Vandetanib | Oral | VEGF/EGFR inhibitor | 25 mg/kg | qd | Not approved | Xenograft-H1975 cells in female athymic nude mice | Inhibition of tumor growth (not dramatic) | 50–145 mg/m2 | qd | Negative | [69] |
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BIBW2992 | Oral | HER2/EGFR inhibitor | 20 mg/kg | qd | October 2010 Phase III clinical trial |
Xenograft-H1975 cells in female athmyic NMRI-nu/nu mice Transgenic-CCSP-rtTA; Tet-07-EGFRL858R |
Dramatic tumor regression T/C ratio 2% | 20–70 mg | D1, 8, 15 q4 weeks | Positive | [37, 70] |
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Crizotinib | Oral | ALK inhibitor | 10 mg/kg | qd | Phase III clinical trials | Transgenic-SP-C-EML4-ALK in C57BL/6J mice | Tumor regression and increase in median survival | 250 mg | 2 d × 6 months | Positive | [57, 71, 72] |
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Navelbine (Vinorelbine) | Oral, IV |
Antimicrotubule chemotherapy |
1.25–5 mg/kg | qd × 9 days | 1994 | Immune-C57B1 mice used for transplantation of LLC | 72.7% inhibition of tumor growth | 25–30 mg/m2 | q weekly | Positive | [73, 74] |
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Paclitaxel | IV | Antimicrotubule chemotherapy |
12–24 mg/kg | qd × 5 days | 1992 | Xenograft-A549, NCI-H23, NCI-H460, DMS-273, NCI-H226, and DMS-114 cells in nude mice | Significant tumor regression, more effective than cisplatin | 135 mg/m2 | q3 weeks | Positive | [36, 75] |
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Abraxane | IV | Antimicrotubule chemotherapy |
250 mg/kg IP | qd × 3 weeks | Phase III clinical trials for lung cancer | Xenograft-H460 cells in female athymic nu/nu mice | Significant tumor regression | 260 mg/m2 | q3 weeks | Positive | [23, 34] |
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Gemcitabine | IV | Nucleoside analog chemotherapy | 50–160 mg/kg | q3-4 days | 2006 | Xenograft-A549 and H1299 cells in female nude mice | Reduced mean tumor double time by 50% in 13 days | 1000 mg/m2 | D1, 8, 15 q28 days | Positive | [32, 76] |
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Pemetrexed | IV | Folate antimetabolite chemotherapy | 30 mg/kg | q3-4 days | 2004 | Xenograft-H460 cells in female athymic nude | Tumor regression duration and dose dependent | 500 mg/m2 | q21 days | Positive | [35, 77] |
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Doxorubicin | IV | Anthracycline antibiotic chemotherapy | 3.0–12 mg/kg | qd | 1950's |
Xenograft-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/m2 | q21–28 days | Positive | [41, 78] |
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Cisplatin | IV | Platinum-based chemotherapy | 7 mg/kg I.P | qd × 2 weeks q4 weeks | 1969 |
Xenograft-A549, H1299 nude mice Transgenic-LSLK-RasG12D on 129svJae background |
Significantly reduced tumor burden, but left long-term resistance | 60 to 100 mg/m2 | q21 days | Positive | [32, 79, 80] |
| |||||||||||
Carboplatin | IV | Platinum-based chemotherapy | 50 mg/kg I.P. | qd | 1989 |
Xenograft-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 year | 200–360 mg/m2 | q4 weeks | Positive | [32, 40, 81] |
| |||||||||||
Etoposide | IV, oral |
DNA topoisomerase II inhibitor | 1–32 mg/kg | qd × 5 days | 1960's | Xenograft-H460 cells in female athmyic nude mice | Tumor growth regression | 100 mg/m2 IV 200 mg/m2 PO |
q3 weeks | Positive | [82, 83] |
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Bevacizumab | IV | Monoclonal antibody VEGF-A inhibitor | 5 mg/kg | qd × 4 weeks | 2004 | Xenograft-H1299 cells in athymic BALB/c female nude mice | Reduced vascularity, reduced interstitial pressure and tumor growth | 15 mg/kg | q3 weeks | Positive | [84, 85] |
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Sunitinib | oral | Multitargeted RTK inhibitor (VEGF, CKit, PDGFα, cRET) | 40 mg/kg | qd × 6 weeks | Phase II clinical trials for lung cancer | Xenograft-NCI-H226, NCI-H526 or NCI-H82 in athmyic female nu/nu mice | Significant tumor growth regression | 37.5–50 mg | continuous qd or qd × 4 weeks q6 weeks | Negative | [42, 86] |
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Sorafinib | oral | Multi-targeted RTK inhibitor (VEGF, CKit, PDGFα, cRET) | 40–80 mg/kg | qd × 9 days | Phase III clinical trials for lung cancer | Xenograft-H460, A549, NCI-H23 cells in female NCr-nu/nu mice | Significant tumor growth regression | 400 mg | bid | Negative | [33, 87] |
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Cetuximab | IV | Monoclonal antibody EGFR inhibitor | 20 μL/g | q3 weeks | 2008 | Xenograft-A549, NCI-H358, HCC-827, H1975, H460 cells in female athmyic nu/nu mice | Significant tumor growth inhibition | 250–400 mg/m2 | 400 mg/m2— 250 mg/m2 q weekly |
Negative | [28, 88] |