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INNOVAZIONI TERAPEUTICHE IN ONCOLOGIA MEDICA
CAGLIARI 23-24 GIUGNO 2005
LE TERAPIE A TARGET MOLECOLARE:
UNA EVOLUZIONE EPOCALE DELLA
TERAPIA ANTINEOPLASTICA
GIOVANNI MANTOVANI
CATTEDRA DI ONCOLOGIA MEDICA
UNIVERSITA’ DEGLI STUDI DI CAGLIARI
THE MOLECULARLY TARGETED
ANTICANCER TREATMENT

The so-called molecularly targeted anticancer
treatment is based on compounds that interefere
with cell targets directly connected with
pathogenetic events. Such therapies are expected
to target specifically tumor cells, thus allowing
for strong anticancer effects and minimal
toxicities

The possible targets are represented
by:
 the
interaction between the ligand (growth
factor) and its specific receptor with the
consequent activation of a cascade of
biochemical events leading to the
transduction of the cell proliferating signal
from the membrane surface to the nucleus;
 the cell cycle checkpoint, acting by a negative
counterregulation
 the apoptosis, by using proapoptotic
molecules
 (neo)angiogenesis
through angiogenesis
inhibitors
 the immune compartment of the host, by
modulating his immune response
EGFR INHIBITION
(Harari PM, Huang SM. Clin Can Res 10:428, 2004)
*
*HRPC: hormone-refractory prostate cancer
(TK INHIB)
 Erlotinib (Tarceva)
EGGR (TK INHIB)
MAIN CURRENT CLINICAL APPLICATIONS 2005

GEFITINIB




MONOTHERAPY (3rd LINE IN NSCLC)
ISEL study in adjuvant setting: negative
Colorectal cancer, breast cancer, brain tumor
ERLOTINIB

MONOTHERAPY IN RECURRENT NSCLC after failure of at least
one prior chemotherapy regimen (NCIC CTG study)

BR.21: a randomised phase III trial of Tarceva following chemotherapy in
advanced NSCLC

MONOTHERAPY IN BAC (Yoshimura A, Gan To Kagaku Ryoho. 2004
Mar;31(3):318-21.)
IN COMBINATION WITH CHEMOTHERAPY IN ADVANCED
PANCREATIC CANCER (Moore MJ, NCI-CTG – Study PA.3, ASCO
2005)

MAIN CURRENT CLINICAL APPLICATIONS 2005





ERLOTINIB + BEVACIZUMAB in advanced refractory
NSCLC
ERLOTINIB + BEVACIZUMAB in metastatic breast cancer
(phase II study)
ERLOTINIB + BEVACIZUMAB in metastatic RCC
ERLOTINIB combined with CISPLATIN and
GEMCITABINE in advanced NSCLC (TALENT STUDY:
negative)
ERLOTINIB combined with CARBOPLATIN and
PACLITAXEL in advanced NSCLC (TRIBUTE STUDY:
negative)
MAIN CURRENT CLINICAL APPLICATIONS 2005
CETUXIMAB
 CETUXIMAB + HIGH DOSE RADIATION IN
ADVANCED HEAD AND NECK SCC
 CETUXIMAB +/- IRINOTECAN IN
METASTATIC REFRACTORY CRC (BOND I
TRIAL)
 FOLFOX/FOLFIRI +/- CETUXIMAB FIRST
LINE IN METASTATIC CRC (CALGB TRIAL)
MAIN CURRENT CLINICAL APPLICATIONS 2005
BEVACIZUMAB
PHASE III TRIALS






Bolus IFL +/- BEVACIZUMAB FIRST LINE IN METASTATIC CRC (Hurwitz,
NEJM 2004)
BEVACIZUMAB +/- FOLFOX4 vs FOLFOX4 SECOND LINE IN
METASTATIC CRC (E3200)
PACLITAXEL + CARBOPLATIN +/- BEVACIZUMAB IN ADVANCED NON
SQUAMOUS NSCLC (E4599)
CAPEOX/FOLFOX +/- BEVACIZUMAB FIRST LINE IN METASTATIC CRC
(SWOG 0303)
BEVACIZUMAB + CETUXIMAB +/- IRINOTECAN THIRD LINE IN
METASTATIC CRC (BOND II TRIAL)
BEVACIZUMAB IN RCC
*
*HRPC: hormone-refractory prostate cancer
Thank you for your attention
and interest!