What are the reasons for negative phase III trials of molecular-target-based drugs?

Cancer Science

Volumn 95, Issue 10, 2004, Pages 772-776

  Saijo, Nagahiro ^a  

^a NATIONAL CANCER CENTER HOSPITAL EAST   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOGENESIS INHIBITOR; ANTINEOPLASTIC AGENT; BCR ABL PROTEIN; BEVACIZUMAB; CARBOPLATIN; CYCLIN DEPENDENT KINASE; DOCETAXEL; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ERLOTINIB; ETOPOSIDE; GEFITINIB; IMATINIB; ISIS 3521; MARIMASTAT; MATRIX METALLOPROTEINASE; MATRIX METALLOPROTEINASE INHIBITOR; OBLIMERSEN; PACLITAXEL; PRINOMASTAT; PROTEIN FARNESYLTRANSFERASE; PROTEIN KINASE C; PROTEIN KINASE C INHIBITOR; RITUXIMAB; SEMAXANIB; TANOMASTAT; THALIDOMIDE; TRASTUZUMAB; UNINDEXED DRUG; VASCULOTROPIN; VASCULOTROPIN INHIBITOR;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; BREAST CANCER; CANCER INHIBITION; CANCER RESEARCH; CANCER SURVIVAL; CHRONIC MYELOID LEUKEMIA; CLINICAL STUDY; CLINICAL TRIAL; DRUG EFFICACY; DRUG INDICATION; DRUG MECHANISM; DRUG RECEPTOR BINDING; DRUG RESEARCH; DRUG TARGETING; GASTROINTESTINAL STROMAL TUMOR; GENE MUTATION; HUMAN; LUNG NON SMALL CELL CANCER; LUNG SMALL CELL CANCER; MOLECULAR BIOLOGY; OUTCOMES RESEARCH; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; REVIEW; THROMBOCYTOPENIA; TREATMENT PLANNING;

ANTINEOPLASTIC AGENTS; CLINICAL TRIALS; CLINICAL TRIALS, PHASE III; DRUG DELIVERY SYSTEMS; DRUG DESIGN; HUMANS; TREATMENT OUTCOME;

EID: 9144254526     PISSN: 13479032     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1349-7006.2004.tb02180.x     Document Type: Review

References (26)

1. Saijo N. The molecular biology and signal transduction of epidermal growth factor receptor. New Dev Lung Cancer 2003; 1 3-6.
2. Sekine I, Saijo N. Growth-stimulting pathways in lung cancer: implications for targets of therapy. Clin Lung Cancer 2001; 2 299-306.
3. Saijo N, Tamura T, Yamamoto N, Nishio K. New strategies for cancer therapy in 21st century. Cancer Chemother Pharmacol 2001; 48: S102-6.
4. Schilsky RL. Endpoints in cancer clinical trials and the drug approval process. Clin Cancer Res 2002; 8: 935-8.
5. Stadler WM, Ratain MJ. Development of target based antineoplastic agents. Invest New Drugs 2000; 18: 7-16.
6. Fox E, Curt GA, Balis FM. Clinical trial design for target-based therapy. Oncologist 2002; 7: 401-9.
7. Gardner SN, Ferandes M. Cytostatic anticancer drug development. J Exp Ther Oncol 2004; 4: 9-18.
8. Saijo N, Tamura T, Nishio K. Problems in the development of target-based drugs. Cancer Chemother Pharmacol 2000; 46: S43-5.
9. Saijo N, Tamura T, Nishio K. Strategy for the development of novel anticancer drugs. Cancer Chemother Pharmacol 2003; 52: S97-101.
10. Druker BJ, Sawyers CL, Kantarjian H, Resta DJ, Reese SF, Ford JM, Capdeville R, Talpaz M. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 2001; 344: 1038-42.
11. Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, Lydon NB, Kantarjian H, Capdeville R, Ohno-Jones S, Sawyers CL. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2002; 344: 1031-7.
12. Slamon DJ, Leyland-Jones B, Shak S et al. Use of chemotherapy plus a monoclonal antibody against Her2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2004; 344 783-92.
13. Coiffier B, Lepage E, Briere J et al. CHOP chemotherapy plus rituximub compared with CHOP alone in elderly patients with diffuse B-cell lymphoma. N Engl J Med 2002; 346: 235-42.
14. Bevacizumab (anti VEGFAb) prolongs survival in first line CRC. ASCO 2003; abstract.
15. Shepherd FA, Giaccone G, Seymour L, Debruyne C, Bezjak A, Hirsh V, Smylie M, Rubin S, Martins H, Lamont A, Krzakowski M, Sadura A, Zee B. Prospective, randomized, double-blind, placebo-controlled trial of marimastat after response to firstline chemotherapy in patients with small-cell lung cancer: a trial of the National Cancer Center Institute of Canada-clinical trials group and European Organization for Research and Treatment of Cancer. J Clin Oncol 2002; 20: 4434-9.
16. Gatzemeier U, Groth G, Hirsh V et al. Gemcitabine/cisplatin alone and with trastuzumab (Herceptin) in patients with non-small cell lung cancer overexpressing HER2: results of a randomised phase II study. Proc Am Soc Clin Oncol 2002; 21: 297a (abstr 1185).
17. Johnson BE, Fischer T, Fischer B, Dunlop D, Rischin D, Silberman S, Kowalski MO, Sayles D, Dimitrijevic S, Fletcher C, Hornick J, Salgia R, Le Chevalier T. Phase II study of imatinib in patients with small cell lung cancer. Clin Cancer Res 2003; 9: 5880-7.
18. Naruse I, Fukumoto H, Saijo N, Nishio K. Enhanced anti-tumor effect of trastuzumab in combination with cisplatin. Jpn J Cancer Res 2002; 93: 574-81.
19. Lynch TJ, Raju R, Lind M, Riviere A, Gatzemeier U, Drorr A, Holmlund J, Yuen A, Sikic B. Randomized phase III trial of chemotherapy and antisense oligonucleotide LY900003 (ISIS 3521) in patients with advanced NSCLC: initial report. Proc Am Soc Clin Oncol 2003; 22 623 (abstr 2504).
20. Rubin C, Kosloff M, Edelman MJ, Hoffman PC, Szeto L, Vokes EE. Phase I study of G3139 (oblimersen sodium), carboplatin, and etoposide in previously untreated extensive stage small cell lung cancer (SCLC). Proc Am Soc Clin Oncol 2003; 22: 631 (abstr 2538).
21. Herbst RS, Giaccone G, Schiller JH, Natale RB, Miller V, Manegold C, Scagliotti G, Rosell R, Oliff I, Reeves JA, Wolf MK, Krebs AD, Averbuch SD, Ochs JS, Grous J, Fandi A, Johnson DH. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial - INTACT 2. J Clin Oncol 2004; 22 785-94.
22. Giaccone G, Herbst RS, Manegold C, Scagliotti G, Rosell R, Miller V, Natale RB, Schiller JH, von Pawel J, Pluzanska A, Gatzemeier U, Grous J, Ochs JS, Averbuch SD, Wolf MK, Rennie P, Fandi A, Johnson DH. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial - INTACT 1. J Clin Oncol 2004; 22: 777-84.
23. Saijo N. Translational study in cancer research. Intern Med 2003; 41: 770-3.
24. Saijo N, Nishio K, Tamura T. Translational and clinical studies of target-based cancer chemotherapy. Int J Clin Oncol 2003; 8: 187-92.
25. Paez JM, Janne PA, Lee JC, Tracy S, Geulich H, Gabriel S, Heman P, Key FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Seller WR, Johnson BE, Meyerson M. EGFR mutation in lung cancer: correlation with clinical response to Gefitinib therapy. Science 1099314, April 30, 2004.
26. Lynch T, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brain BS, Brannigan W, Harris PL, Haselat SM, Supko JG, Haluska FG, Haselat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA. N Engl J Med 2004; 350: 2129-39.