1. 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

2. 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 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 MOLECULARLY TARGETED ANTICANCER TREATMENT

3. The possible targets are represented by: 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 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 cell cycle checkpoint, acting by a negative counterregulation the apoptosis, by using proapoptotic molecules the apoptosis, by using proapoptotic molecules

4. (neo)angiogenesisthrough angiogenesis inhibitors (neo)angiogenesisthrough angiogenesis inhibitors the immune compartment of the host, by modulating his immune response the immune compartment of the host, by modulating his immune response

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

48. *HRPC: hormone-refractory prostate cancer *

54.  Erlotinib (Tarceva) EGGR (TK INHIB) (TK INHIB)

59. 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

60. 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)

61. CETUXIMAB CETUXIMAB + HIGH DOSE RADIATION IN ADVANCED HEAD AND NECK SCC CETUXIMAB + HIGH DOSE RADIATION IN ADVANCED HEAD AND NECK SCC CETUXIMAB +/- IRINOTECAN IN METASTATIC REFRACTORY CRC (BOND I TRIAL) CETUXIMAB +/- IRINOTECAN IN METASTATIC REFRACTORY CRC (BOND I TRIAL) FOLFOX/FOLFIRI +/- CETUXIMAB FIRST LINE IN METASTATIC CRC (CALGB TRIAL) FOLFOX/FOLFIRI +/- CETUXIMAB FIRST LINE IN METASTATIC CRC (CALGB TRIAL) MAIN CURRENT CLINICAL APPLICATIONS 2005

62. 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

63. *HRPC: hormone-refractory prostate cancer *

65. Thank you for your attention and interest!