INNOVAZIONI TERAPEUTICHE IN ONCOLOGIA MEDICACAGLIARI 23-24 GIUGNO 2005

LE TERAPIE A TARGET MOLECOLARE: LE TERAPIE A TARGET MOLECOLARE: UNA EVOLUZIONE EPOCALE DELLA UNA EVOLUZIONE EPOCALE DELLA

TERAPIA ANTINEOPLASTICATERAPIA ANTINEOPLASTICAGIOVANNI MANTOVANI

CATTEDRA DI ONCOLOGIA MEDICAUNIVERSITA’ DEGLI STUDI DI CAGLIARI

The so-called molecularly targeted The so-called molecularly targeted anticancer treatment is based on anticancer treatment is based on compounds that interefere with cell compounds that interefere with cell targets directly connected with targets directly connected with pathogenetic events. Such therapies pathogenetic events. Such therapies are expected to target specifically are expected to target specifically tumor cells, thus allowing for strong tumor cells, thus allowing for strong anticancer effects and minimal anticancer effects and minimal toxicities toxicities

THE MOLECULARLY TARGETED ANTICANCER

TREATMENT

The possible targets are The possible targets are represented by:represented by: the interaction between the ligand the interaction between the ligand

(growth factor) and its specific receptor (growth factor) and its specific receptor with the consequent activation of a with the consequent activation of a cascade of biochemical events leading cascade of biochemical events leading to the transduction of the cell to the transduction of the cell proliferating signal from the membrane proliferating signal from the membrane surface to the nucleus;surface to the nucleus;

the cell cycle checkpoint, acting by a the cell cycle checkpoint, acting by a negative counterregulationnegative counterregulation

the apoptosis, by using proapoptotic the apoptosis, by using proapoptotic moleculesmolecules

(neo)angiogenesis(neo)angiogenesis through through angiogenesis inhibitorsangiogenesis inhibitors

the immune compartment of the the immune compartment of the host, by modulating his immune host, by modulating his immune responseresponse

EGFR INHIBITION

(Harari PM, Huang SM. Clin Can Res 10:428, 2004)

*HRPC: hormone-refractory prostate cancer

*

Erlotinib (Tarceva) EGGR (TK INHIB)

(TK INHIB)

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

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)

CETUXIMABCETUXIMAB CETUXIMAB + HIGH DOSE RADIATION CETUXIMAB + HIGH DOSE RADIATION

IN ADVANCED HEAD AND NECK SCCIN ADVANCED HEAD AND NECK SCC CETUXIMAB +/- IRINOTECAN IN CETUXIMAB +/- IRINOTECAN IN

METASTATIC REFRACTORY CRC METASTATIC REFRACTORY CRC (BOND I TRIAL)(BOND I TRIAL)

FOLFOX/FOLFIRI +/- CETUXIMAB FOLFOX/FOLFIRI +/- CETUXIMAB FIRST LINE IN METASTATIC CRC FIRST LINE IN METASTATIC CRC (CALGB TRIAL)(CALGB TRIAL)

MAIN CURRENT CLINICAL APPLICATIONS 2005

MAIN CURRENT CLINICAL APPLICATIONS 2005

BEVACIZUMABPHASE 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 attentionThank you for your attentionand interest!and interest!