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Table 3 FDA and EMA drug description of anticancer drugs of lead compounds

From: Repurposing of anticancer drugs: in vitro and in vivo activities against Schistosoma mansoni

Drug

Cmax Single oral dose (or otherwise as indicated)

t1/2 Single oral dose (or otherwise as indicated)

LD50 Single oral dose toxicity

Indication

Mechanism of action

Dosage

Reference (health agency)

Afatinib (GIOTRIF®)

NA

37 h (after repeated dosing given to patients)

NA

Metastatic non-small cell lung cancer

Irreversible inhibitor of tyrosine kinase autophos-phorylation

40 mg/day

FDA

 

397 nmol/l (1×8 mg/kg given to rats)

4.5 h (1×8 mg/kg given to rats)

382–763 mg/kg (mice)

EMA

Bosutinib (BOSULIF®)

0.2 μg/ml (500 mg given to patients on 15 consecutive days)

22 h (patients; dose not indicated)

NA

Chronic, accelerated, or blast phase Ph + chronic myelogenous leukemia

Tyrosine kinase inhibitor

500 mg/day

FDA

 

NA

2.5–5.4 h (mice and rats; dose not indicated)

>2000 mg/kg (mice and rats)

EMA

Crizotinib (XALKORI®)

100–135 ng/ml (250 mg given to patients)

42 h (250 mg given to patients)

>500 mg/kg (rats)

Metastatic non-small cell lung cancer

Tyrosine kinase inhibitor

2×250 mg/day

FDA

 

NA

5.8–13 h (rats; dose not indicated)

NA

EMA

Gefitinib (IRESSA®)

NA

48 h (healthy volunteers; dose not indicated)

NA

Non-small cell lung cancer

Multiple tyrosine kinase inhibitor

250 mg/day

FDA

 

1 μg/ml (after 20 mg/kg given to rats); 0.1 μg/ml (after 250 mg/kg given to healthy volunteers)

10 h (rats; dose not indicated); 30 h (after 250 mg/kg given to healthy volunteers)

Around 2000 mg/kg (rats); >1000 mg/kg (dogs)

EMA

Ponatinib (INCLUSIG®)

6 h (patients; dose not indicated)

24 h (patients; dose not indicated)

>2000 mg/kg (mice)

Chronic myeloid leukemia

Tyrosine kinase inhibitor

45 mg/day

FDA

 

4 h (patients; dose not indicated)

22 h (patients; dose not indicated)

NA

EMA

Regorafenib (STIVAGRA®)

12.5 μg/ml (after 160 mg given to patients)

24 h (after 160 mg given to patients)

NA

Metastatic colon cancer

Multiple protein kinase inhibitor

160 mg/day for first 21 days of a 28-day cycle

FDA

 

3.96 mg/l (multiple treatment: 160 mg/day for 3 weeks given to patients)

2 h (multiple treatment; 160 mg/day for 3 weeks given to patients)

>250 mg/kg (mice and rats)

 

EMA

Sorafenib (NEXAVAR®)

NA

25–48 h

NA

Liver, kidney, thyroid cancer

Multiple protein kinase inhibitor

2×400 mg/day

FDA

 

0.55 mg/l (after 400 mg given to patients)

22.3 h (after 400 mg given to patients)

>1460 mg/kg (mice and rats)

EMA

Sunitinib (SUTENT®)

NA

40–60 h (parent drug in healthy volunteers; 80–110 h (active metabolite in healthy volunteers (dose not indicated)

NA

Gastrointestinal stromal tumor, renal cell carcinoma, well-differentiated pancreatic neuroendocrine tumors

Inhibitor of multiple receptor tyrosine kinases

50 mg/d for the first 28 days of a 42-day cycle

FDA

 

NA

NA

>500 mg/kg (mice and rats)

EMA

Trametinib (MEKINIST®)

NA

Estimated: 3.9–4.8 days (patients; dose not indicated)

NA

Unresectable or metastatic melanoma with BRAF V600E or V600K mutations

Kinase inhibitor

2 mg/day

FDA

 

22.2 ng/ml (steady state after 2 mg/daygiven to healthy volunteers)

5.3 days (healthy volunteers; dose not indicated)

NA

EMA

Tamoxifen citrate (NOLVADEX®)

40 ng/ml (after 20 mg given to rats)

5–6 days (after 20 mg given to rats)

NA

Breast cancer

Nonsteroidal antiestrogen

NA

FDA

 

NA

NA

NA

20 mg/day

EMA

Vandetanib (CAPRELSA®)

NA

NA

NA

Medullary thyroid cancer

Multiple tyrosine kinase inhibitor

300 mg/day

FDA

 

NA

19 days (after 300 mg given to healthy volunteers)

NA

EMA

  1. NA Not available on the data sheets of the according health agency