[Frontiers in Bioscience S3, 16-22, January 1, 2011]

Targeting EGFR in bilio-pancreatic and liver carcinoma

Maria Elisabetta Fratto1, Daniele Santini1, Bruno Vincenzi1, Nicola Silvestris2, Amalia Azzariti3, Stefania Tommasi3, Alice Zoccoli1, Sara Galluzzo1, Evaristo Maiello4, Giuseppe Colucci2, Giuseppe Tonini1

1Medical Oncology, University Campus Bio-Medico, Rome, 2Medical and Experimental Oncology Unit, Scientific Institute for Research and Treatment of Cancer "Giovanni Paolo II", Bari,3Clinical Experimental Oncology Laboratory, Scientific Institute for Research and Treatment of Cancer "Giovanni Paolo II", 4Medical Oncology Unit, Scientific Institute for Research and Treatment of Cancer "Casa Sollievo della Sofferenza" - San Giovanni Rotondo

TABLES

Table 1. Clinical studies of EGFR inhibitors in BTCs

Author (Reference)

Regimen

Phase

No patients

Line

Results

Comments

Philip et al (10)

Erlotinib

II

42

1,2

RR: 7%

EGFR mutation not tested

PFS: 17%

Paule B et al (12)

Cetuximab+ GEMOX

II

9

2

(PD after GEMOX)

TTP: 4 months

EGFR, erbB-2, EGFR gene copy number assessed

OS: 7 months

Malka D et al (14)

Cetuximab+ GEMOX vs GEMOX

II

101

1

PFS: 61% vs 44%

Blood/tumor EGFR signalling pathway member assessed

Gruenberger B et al (15)

Cetuximab+ GEMOX

II

30

1

RR: 63%

No correlation between K-Ras and response

PFS: 8.3 months

OS: 12.7 months

Ramanathan et al (16)

Lapatinib

II

17

1/2

RR:0%

 

Abbreviations: EGFR: Epidermal Growth Factor Receptor; NS: Not significant; OS: Overall Survival; PFS: Progression-Free Survival.

Table 2. Clinical studies of EGFR inhibitors in HCC

Author (Reference)

Regimen

Phase

No patients

Results

Comments

Philip et al (29)

erlotinib

II

38

PFS at 6 months 32%

EGFR/HER1 expression detected in 88% of the patients.

OS: 13 months

Thomas et al (30)

erlotinib

II

40

PFS at 16 weeks: 43%

No correlation between EGFR expression and outcome

Median OS: 43 weeks

Thomas et al (31)

Erlotinib+bevacizumab

II

40

PFS at 16 weeks: 62.5 %

Median OS: 68 weeks

Zhu et al (2007)

Cetuximab

II

30

No response was observed

 

Gruenwald et al (32)

Cetuximab

II

32

SD: 44%

No correlation with cytogenetic abnormalities for chromosome 1 and 8. p27 and p21 were upregulated simultaneously in 60% (3/5 pts) of responding patients

PFS: 8weeks

Asnacios et al (34)

Cetuximab + GEMOX

II

45

PFS: 4.7 months

OS: 9.5 months

RR: 20%

Abbreviations: EGFR: Epidermal Growth Factor Receptor; OS: Overall Survival; PFS: Progression-Free Survival; RR: Response Rate; SD: Stable Disease

Table 3. Main clinical studies of EGFR inhibitors in pancreatic cancer

Author (Reference)

Regimen

Phase

No patients

Results

Moore MJ et al (37)

Erlotinib+gemcitabine VS Gemcitabine

III

569

OS: 6.24 VS 5.91 months

Vervenne et al (38)

Gemcitabine +Erlotinib VS Gemcitabine + erlotinib+ bevacizumab

III

607

PFS: 3.6 VS 4.6 months (p: 0.0002)

OS: 6 VS 7.1 Months (NS)

Xiong et al (39)

Cetuximab + gemcitabine

II

41 EGFR+

PFS: 3.8 months

OS: 7.1 months

Philip et al (40)

Cetuximab+gemcitabine VS Gemcitabine

III

735

PFS: 3 VS 3.5 months (NS)

OS: 6 VS 6.5 Months (NS)

Kindler et al (41)

Gemcitabine + Bevacizumab +Erlotinib VS Gemcitabine + bevacizumab + cetuximab

II

139

PFS: 5.0 VS 5.1 months (NS)

1 year-OS: 30% VS 35% (NS)

Abbreviations: EGFR: Epidermal Growth Factor Receptor; NS: Not significant; OS: Overall Survival; PFS: Progression-Free Survival.