Cancer chemotherapy: A critical analysis of its 60 years of history

Critical Reviews in Oncology/Hematology - Tập 84 - Trang 181-199 - 2012
Darío Galmarini1, Carlos M. Galmarini1, Felipe C. Galmarini1
1Fundación Marcel Dargent – Escuela Sudamericana de Oncología, Buenos Aires, Argentina

Tài liệu tham khảo

Farber, 1948, Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid, N Engl J Med, 238, 787, 10.1056/NEJM194806032382301 Gilman, 1946, Therapeutic applications of chemical warfare agents, Fed Proc, 5, 285 Law, 1951, Response of a resistant variant of leukemic cells to an antagonist of pteroylglutamic acid, Proc Soc Exp Biol Med, 77, 340, 10.3181/00379727-77-18773 Philips, 1950, Recent contributions to the pharmacology of bis(2-haloethyl) amines and sulfides, J Pharmacol Exp Ther, 99, 281 Seeger, 1947, Antagonist for pteroylglutamic acid, J Am Chem Soc, 69, 2567, 10.1021/ja01202a519 Stevens, 1950, Biological action of ‘mustard gas’ compounds, Nature, 166, 1019, 10.1038/1661019a0 Farber, 1949, Some observations on the effect of folic acid antagonists on acute leukemia and other forms of incurable cancer, Blood, 4, 160, 10.1182/blood.V4.2.160.160 Elion, 1951, Antagonists of nucleic acid derivatives. VI. Purines, J Biol Chem, 192, 505, 10.1016/S0021-9258(19)77771-0 Burchenal, 1953, Clinical evaluation of a new antimetabolite, 6-mercaptopurine, in the treatment of leukemia and allied diseases, Blood, 8, 965, 10.1182/blood.V8.11.965.965 Heidelberger, 1957, Fluorinated pyrimidines, a new class of tumour-inhibitory compounds, Nature, 179, 663, 10.1038/179663a0 Li, 1958, Therapy of choriocarcinoma and related trophoblastic tumors with folic acid and purine antagonists, N Engl J Med, 259, 66, 10.1056/NEJM195807102590204 Chabner, 2005, Timeline: chemotherapy and the war on cancer, Nat Rev Cancer, 5, 65, 10.1038/nrc1529 Morrison, 2010, Cancer chemotherapy: an annotated history, J Vet Intern Med, 24, 1249, 10.1111/j.1939-1676.2010.0590.x Gilman, 1946, The biological actions and therapeutic applications of the B-chloroethyl amines and sulfides, Science, 103, 409, 10.1126/science.103.2675.409 Goodman, 1946, Nitrogen mustard therapy; use of methyl-bis (beta-chloroethyl) amine hydrochloride and tris (beta-chloroethyl) amine hydrochloride for Hodgkin's disease, lymphosarcoma, leukemia and certain allied and miscellaneous disorders, J Am Med Assoc, 132, 126, 10.1001/jama.1946.02870380008004 Gilman, 1963, The initial clinical trial of nitrogen mustard, Am J Surg, 105, 574, 10.1016/0002-9610(63)90232-0 Gellhorn, 1956, Chlorambucil in treatment of chronic lymphocytic leukemia and certain lymphomas, J Am Med Assoc, 162, 178, 10.1001/jama.1956.02970200026006 Pinkel, 1961, Cyclophosphamide in children with cancer, Cancer Chemother Rep, 12, 187 Watson, 1953, Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid, Nature, 171, 737, 10.1038/171737a0 Lajtha, 1969, Proliferative capacity of hematopoietic stem cells Lesher, 1969 Bernard, 1966, A new agent active in the treatment of acute leukemia: cytosine arabinoside, Presse Med, 74, 799 Bonadonna, 1969, Clinical evaluation of adriamycin, a new antitumour antibiotic, Br Med J, 3, 503, 10.1136/bmj.3.5669.503 Dimarco, 1964, ‘Daunomycin’, a new antibiotic of the rhodomycin group, Nature, 201, 706, 10.1038/201706a0 Falkson, 1965, Natulan (Procarbazine) combined with radiotherapy in management of inoperable malignant melanoma, Br Med J, 2, 1473, 10.1136/bmj.2.5476.1473 Johnson, 1963, The vinca alkaloids: a new class of oncolytic agents, Cancer Res, 23, 1390 Mathe, 1962, Trial therapy of Hodgkin's disease and other malignant reticulo-histiocytic diseases by vincaleukoblastin, Presse Med, 70, 1349 Umezawa, 1967, Studies on bleomycin, Cancer, 20, 891, 10.1002/1097-0142(1967)20:5<891::AID-CNCR2820200550>3.0.CO;2-V Felix, 1975, Clinical study of the new podophyllotoxin derivative, 4′-demethylepipodophyllotoxin 9-(4,6-o-ethylidene- beta-d-glucopyranoside) (NSC-141540; VP-16-213), in solid tumors, Cancer Chemother Rep, 59, 737 Lippman, 1973, Clinical trials of cis-diamminedichloroplatinum (NSC-119875), Cancer Chemother Rep, 57, 191 Holland, 1954, The chemical control of cancer, Public Health Rep, 69, 1151, 10.2307/4588981 Baserga, 1962, Uptake of tritiated thymidine by human tumors in vivo, Lab Invest, 11, 360 Johnson, 1960, A radioautographic study of a human brain and glioblastoma multiforme after the in vivo uptake of tritiated thymidine, Cancer, 13, 636, 10.1002/1097-0142(196005/06)13:3<636::AID-CNCR2820130328>3.0.CO;2-R Johnson, 1960, Labeling of human tumor cells in vivo by tritiated thymidine, Lab Invest, 9, 460 Killmann, 1962, Cell proliferation in multiple myeloma studied with tritiated thymidine in vivo, Lab Invest, 11, 845 Lala, 1965, Measurement of DNA-synthesis time in myeloid–erythroid precursors, Exp Cell Res, 38, 626, 10.1016/0014-4827(65)90386-1 Lipkin, 1963, Cell proliferation kinetics in the gastrointestinal tract of man. I. Cell renewal in colon and rectum, J Clin Invest, 42, 767, 10.1172/JCI104769 Clarkson, 1965, Kinetics of proliferation of cancer cells in neoplastic effusions in man, Cancer, 18, 1189, 10.1002/1097-0142(196510)18:10<1189::AID-CNCR2820181002>3.0.CO;2-8 McKinna, 1967, An experimental approach to adjuvant chemotherapy in carcinoma of the rectum and colon, Proc R Soc Med, 60, 212 Rubini, 1960, The metabolism and fate of tritiated thymidine in man, J Clin Invest, 39, 909, 10.1172/JCI104111 Hoffman, 1967, In vivo studies of DNA synthesis in human normal and tumor cells, Cancer Res, 27, 898 Skipper, 1965, The effects of chemotherapy on the kinetics of leukemic cell behavior, Cancer Res, 25, 1544 Skipper, 1954, Partial reversal of the antileukemic activity of A-methopterin by cortisone, Cancer Res, 14, 86 Skipper, 1964, Experimental evaluation of potential anticancer agents. XIII. On the criteria and kinetics associated with “curability” of experimental leukemia, Cancer Chemother Rep, 35, 1 Wilcox, 1966, Experimental evaluation of potential anticancer agents XV. On the relative rates of growth and host kill of “single” leukemia cells that survive in vivo cytoxan therapy, Cancer Res, 26, 1009 Skipper, 1957, Some biochemical problems of cancer chemotherapy, Nature, 179, 1159, 10.1038/1791159a0 Skipper, 1954, Attempts at dual blocking of biochemical events in cancer chemotherapy, Cancer Res, 14, 503 Leibman, 1955, The metabolism of P32-labeled ribonucleotides in tissue slices and cell suspensions, J Biol Chem, 216, 823, 10.1016/S0021-9258(19)81436-9 Rutman, 1954, Studies in 2-acetylaminofluorene carcinogenesis. III. The utilization of uracil-2-C14 by preneoplastic rat liver and rat hepatoma, Cancer Res, 14, 119 Mathe, 1966, Extensive histological and cytological survey of patients with acute leukaemia in “complete remission”, Br Med J, 1, 640, 10.1136/bmj.1.5488.640 Report to the British Medical Research Council by their Tuberculosis Chemotherapy Trials Committee: Various combinations of isoniazid with streptomycin or with P.A.S. in the treatment of pulmonary tuberculosis. Br Med J 1955;1:465-6. Li, 1960, Effects of combined drug therapy on metastatic cancer of the testis, JAMA, 174, 1291, 10.1001/jama.1960.03030100059013 De Lena, 1973, Therapy of metastatic mammary carcinoma with cyclophosphamide, methotrexate, vincristine and fluorouracil, Tumori, 59, 11, 10.1177/030089167305900102 Einhorn, 1977, Cis-diamminedichloroplatinum, vinblastine, and bleomycin combination chemotherapy in disseminated testicular cancer, Ann Intern Med, 87, 293, 10.7326/0003-4819-87-3-293 Einhorn, 1979, Combination chemotherapy in disseminated testicular cancer: the Indiana University experience, Semin Oncol, 6, 87 Frei, 1965, The effectiveness of combinations of antileukemic agents in inducing and maintaining remission in children with acute leukemia, Blood, 26, 642, 10.1182/blood.V26.5.642.642 Devita, 1970, Combination chemotherapy in the treatment of advanced Hodgkin's disease, Ann Intern Med, 73, 881, 10.7326/0003-4819-73-6-881 Bonadonna, 1975, Combination chemotherapy of Hodgkin's disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP, Cancer, 36, 252, 10.1002/1097-0142(197507)36:1<252::AID-CNCR2820360128>3.0.CO;2-7 Frei, 1958, A comparative study of two regimens of combination chemotherapy in acute leukemia, Blood, 13, 1126, 10.1182/blood.V13.12.1126.1126 Goldie, 1979, A mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate, Cancer Treat Rep, 63, 1727 Li, 1960, Current status of cancer chemotherapy, J Natl Med Assoc, 52, 315 Mathe, 1968, Operational research in anticancer chemotherapy. Chemotherapy and strategy of treatment of cancer, Bull Mem Soc Med Hop Paris, 119, 133 Cole, 1952, Recurrence in carcinoma of the colon and proximal rectum following resection for carcinoma, AMA Arch Surg, 65, 264, 10.1001/archsurg.1952.01260020277008 Fisher, 1955, The cytologic demonstration and significance of tumor cells in the mesenteric venous blood in patients with colorectal carcinoma, Surg Gynecol Obstet, 100, 102 Roberts, 1962, Relationship of cancer cell in the circulating blood to operation, Cancer, 15, 232, 10.1002/1097-0142(196203/04)15:2<232::AID-CNCR2820150204>3.0.CO;2-O Rousselot, 1965, Intraluminal chemotherapy adjuvant (HN2 or 5-FU) to operation for cancer of the colon and rectum. Follow-up report of 83 cases, Ann Surg, 162, 407, 10.1097/00000658-196509000-00010 Dwight, 1973, FUDR as an adjuvant to surgery in cancer of the large bowel, J Surg Oncol, 5, 243, 10.1002/jso.2930050307 Holden, 1967, The use of triethylenethiophosphoramide as an adjuvant to the surgical treatment of colorectal carcinoma, Ann Surg, 165, 481, 10.1097/00000658-196704000-00001 Lawrence, 1975, Chemotherapy as an adjuvant to surgery for colorectal cancer, Ann Surg, 181, 616, 10.1097/00000658-197505000-00016 Goldie, 1987, Scientific basis for adjuvant and primary (neoadjuvant) chemotherapy, Semin Oncol, 14, 1 Heuser, 1979, Growth rates of primary breast cancers, Cancer, 43, 1888, 10.1002/1097-0142(197905)43:5<1888::AID-CNCR2820430545>3.0.CO;2-M Shackney, 1978, Growth rate patterns of solid tumors and their relation to responsiveness to therapy: an analytical review, Ann Intern Med, 89, 107, 10.7326/0003-4819-89-1-107 Speer, 1984, A stochastic numerical model of breast cancer growth that simulates clinical data, Cancer Res, 44, 4124 Fisher, 1968, Surgical adjuvant chemotherapy in cancer of the breast: results of a decade of cooperative investigation, Ann Surg, 168, 337, 10.1097/00000658-196809000-00004 Fisher, 1975, 1-Phenylalanine mustard (L-PAM) in the management of primary breast cancer. A report of early findings, N Engl J Med, 292, 117, 10.1056/NEJM197501162920301 Bonadonna, 1976, Combination chemotherapy as an adjuvant treatment in operable breast cancer, N Engl J Med, 294, 405, 10.1056/NEJM197602192940801 Jaffe, 1974, Adjuvant methotrexate and citrovorum-factor treatment of osteogenic sarcoma, N Engl J Med, 291, 994, 10.1056/NEJM197411072911902 Norton, 1976, Predicting the course of Gompertzian growth, Nature, 264, 542, 10.1038/264542a0 Kidwell, 1969, The inheritance of growth and form in the mouse. II. The Gompertz growth equation, Growth, 33, 339 Kopper, 1975, The therapeutic response of three human tumor lines maintained in immune-suppressed mice, Cancer Res, 35, 2704 Laird, 1969, Dynamics of growth in tumors and in normal organisms, Natl Cancer Inst Monogr, 30, 15 Steel, 1966, Analysis of the cell population kinetics of transplanted tumours of widely-differing growth rate, Br J Cancer, 20, 784, 10.1038/bjc.1966.90 Lala, 1972, Age-specific changes in the proliferation of Ehrlich ascites tumor cells grown as solid tumors, Cancer Res, 32, 628 Watson, 1976, The cell proliferation kinetics of the EMT6/M/AC mouse tumour at four volumes during unperturbed growth in vivo, Cell Tissue Kinet, 9, 147 Norton, 1985, Implications of kinetic heterogeneity in clinical oncology, Semin Oncol, 12, 231 Norton, 2005, Conceptual and practical implications of breast tissue geometry: toward a more effective, less toxic therapy, Oncologist, 10, 370, 10.1634/theoncologist.10-6-370 Lyman, 2011, Systematic review of efficacy of dose-dense versus non-dose-dense chemotherapy in breast cancer, non-Hodgkin lymphoma, and non-small cell lung cancer, Crit Rev Oncol Hematol Groffen, 1984, Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22, Cell, 36, 93, 10.1016/0092-8674(84)90077-1 Heisterkamp, 1983, Localization of the c-ab1 oncogene adjacent to a translocation break point in chronic myelocytic leukaemia, Nature, 306, 239, 10.1038/306239a0 Lugo, 1990, Tyrosine kinase activity and transformation potency of bcr-abl oncogene products, Science, 247, 1079, 10.1126/science.2408149 Nowell, 2007, Discovery of the Philadelphia chromosome: a personal perspective, J Clin Invest, 117, 2033, 10.1172/JCI31771 Druker, 2002, Perspectives on the development of a molecularly targeted agent, Cancer Cell, 1, 31, 10.1016/S1535-6108(02)00025-9 Druker, 2006, Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia, N Engl J Med, 355, 2408, 10.1056/NEJMoa062867 O’Brien, 2003, Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia, N Engl J Med, 348, 994, 10.1056/NEJMoa022457 Blanke, 2008, Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT, J Clin Oncol, 26, 620, 10.1200/JCO.2007.13.4403 Blanke, 2008, Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033, J Clin Oncol, 26, 626, 10.1200/JCO.2007.13.4452 Krause, 2005, Tyrosine kinases as targets for cancer therapy, N Engl J Med, 353, 172, 10.1056/NEJMra044389 Verweij, 2004, Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial, Lancet, 364, 1127, 10.1016/S0140-6736(04)17098-0 Johnson, 2003, Phase II study of imatinib in patients with small cell lung cancer, Clin Cancer Res, 9, 5880 Kindler, 2004, Efficacy and safety of imatinib in adult patients with c-kit-positive acute myeloid leukemia, Blood, 103, 3644, 10.1182/blood-2003-06-2071 Druker, 1996, Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells, Nat Med, 2, 561, 10.1038/nm0596-561 Escudier, 2007, Sorafenib in advanced clear-cell renal-cell carcinoma, N Engl J Med, 356, 125, 10.1056/NEJMoa060655 Kantarjian, 2006, Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL, N Engl J Med, 354, 2542, 10.1056/NEJMoa055104 Kantarjian, 2010, Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia, N Engl J Med, 362, 2260, 10.1056/NEJMoa1002315 Llovet, 2008, Sorafenib in advanced hepatocellular carcinoma, N Engl J Med, 359, 378, 10.1056/NEJMoa0708857 Talpaz, 2006, Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias, N Engl J Med, 354, 2531, 10.1056/NEJMoa055229 Saglio, 2010, Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia, N Engl J Med, 362, 2251, 10.1056/NEJMoa0912614 Kris, 2003, Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial, JAMA, 290, 2149, 10.1001/jama.290.16.2149 Mok, 2009, Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma, N Engl J Med, 361, 947, 10.1056/NEJMoa0810699 Shepherd, 2005, Erlotinib in previously treated non-small-cell lung cancer, N Engl J Med, 353, 123, 10.1056/NEJMoa050753 Chapman, 2011, Improved survival with vemurafenib in melanoma with BRAF V600E mutation, N Engl J Med, 364, 2507, 10.1056/NEJMoa1103782 Kwak, 2010, Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer, N Engl J Med, 363, 1693, 10.1056/NEJMoa1006448 Bracarda, 2011, Early detection, prevention and management of cutaneous adverse events due to sorafenib: Recommendations from the Sorafenib Working Group, Crit Rev Oncol Hematol Fojo, 2008, Commentary: novel therapies for cancer: why dirty might be better, Oncologist, 13, 277, 10.1634/theoncologist.2007-0090 Cline, 1971, Cancer chemotherapy, 1 Bonadonna, 1983, Principi di chemioterapia antitumorale, 201 Hait, 2010, Principles of medical oncology Galmarini, 2001, Nucleoside analogues: mechanisms of drug resistance and reversal strategies, Leukemia, 15, 875, 10.1038/sj.leu.2402114 Goldie, 1985, Genetic instability in the development of drug resistance, Semin Oncol, 12, 222 Leonard, 2003, The role of ABC transporters in clinical practice, Oncologist, 8, 411, 10.1634/theoncologist.8-5-411 Lowe, 1994, p53 status and the efficacy of cancer therapy in vivo, Science, 266, 807, 10.1126/science.7973635 Jain, 1998, The next frontier of molecular medicine: delivery of therapeutics, Nat Med, 4, 655, 10.1038/nm0698-655 Galmarini, 2003, Multidrug resistance in cancer therapy: role of the microenvironment, Curr Opin Investig Drugs, 4, 1416 Tredan, 2007, Drug resistance and the solid tumor microenvironment, J Natl Cancer Inst, 99, 1441, 10.1093/jnci/djm135 Galmarini, 2000, Heterogeneous distribution of tumor blood supply affects the response to chemotherapy in patients with head and neck cancer, Microcirculation, 7, 405, 10.1038/sj.mn.7300126 Jain, 1988, Determinants of tumor blood flow: a review, Cancer Res, 48, 2641 Jain, 1994, Barriers to drug delivery in solid tumors, Sci Am, 271, 58, 10.1038/scientificamerican0794-58 Brown, 1998, The unique physiology of solid tumors: opportunities (and problems) for cancer therapy, Cancer Res, 58, 1408 Less, 1997, Geometric resistance and microvascular network architecture of human colorectal carcinoma, Microcirculation, 4, 25, 10.3109/10739689709148315 Sevick, 1989, Viscous resistance to blood flow in solid tumors: effect of hematocrit on intratumor blood viscosity, Cancer Res, 49, 3513 Sevick, 1991, Effect of red blood cell rigidity on tumor blood flow: increase in viscous resistance during hyperglycemia, Cancer Res, 51, 2727 Eskey, 1992, 2H-nuclear magnetic resonance imaging of tumor blood flow: spatial and temporal heterogeneity in a tissue-isolated mammary adenocarcinoma, Cancer Res, 52, 6010 Hamberg, 1994, Spatial heterogeneity in tumor perfusion measured with functional computed tomography at 0.05 microliter resolution, Cancer Res, 54, 6032 Baxter, 1989, Transport of fluid and macromolecules in tumors. I. Role of interstitial pressure and convection, Microvasc Res, 37, 77, 10.1016/0026-2862(89)90074-5 Jain, 1987, Transport of molecules across tumor vasculature, Cancer Metastasis Rev, 6, 559, 10.1007/BF00047468 Boucher, 1990, Interstitial pressure gradients in tissue-isolated and subcutaneous tumors: implications for therapy, Cancer Res, 50, 4478 Jain, 1987, Transport of molecules in the tumor interstitium: a review, Cancer Res, 47, 3039 Tannock, 2002, Limited penetration of anticancer drugs through tumor tissue: a potential cause of resistance of solid tumors to chemotherapy, Clin Cancer Res, 8, 878 Vaupel, 1989, Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review, Cancer Res, 49, 6449 Kim, 2005, Repopulation of cancer cells during therapy: an important cause of treatment failure, Nat Rev Cancer, 5, 516, 10.1038/nrc1650 Zhang, 2011, Tumor-initiating cells and tumor vascularization, Pediatr Blood Cancer, 56, 335, 10.1002/pbc.22886 Demicheli, 1997, Proposal for a new model of breast cancer metastatic development, Ann Oncol, 8, 1075, 10.1023/A:1008263116022 Demicheli, 1994, Local recurrences following mastectomy: support for the concept of tumor dormancy, J Natl Cancer Inst, 86, 45, 10.1093/jnci/86.1.45 Folkman, 1990, What is the evidence that tumors are angiogenesis dependent?, J Natl Cancer Inst, 82, 4, 10.1093/jnci/82.1.4 O’Reilly, 1996, Angiostatin induces and sustains dormancy of human primary tumors in mice, Nat Med, 2, 689, 10.1038/nm0696-689 O’Reilly, 1994, Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma, Cell, 79, 315, 10.1016/0092-8674(94)90200-3 Baum, 2005, Does surgery unfavourably perturb the “natural history” of early breast cancer by accelerating the appearance of distant metastases?, Eur J Cancer, 41, 508, 10.1016/j.ejca.2004.09.031 Demicheli, 2005, Breast cancer recurrence dynamics following adjuvant CMF is consistent with tumor dormancy and mastectomy-driven acceleration of the metastatic process, Ann Oncol, 16, 1449, 10.1093/annonc/mdi280 1996, Duration and reintroduction of adjuvant chemotherapy for node-positive premenopausal breast cancer patients, J Clin Oncol, 14, 1885, 10.1200/JCO.1996.14.6.1885 Castiglione-Gertsch, 1997, Retreating recurrent breast cancer with the same CMF-containing regimen used as adjuvant therapy. The International Breast Cancer Study Group, Eur J Cancer, 33, 2321, 10.1016/S0959-8049(97)10011-9 Valagussa, 1989, Salvage treatments in relapsing resectable breast cancer, Recent Results Cancer Res, 115, 69, 10.1007/978-3-642-83337-3_10 Bardwell, 1994, Recent insights on DNA repair. The mechanism of damaged nucleotide excision in eukaryotes and its relationship to other cellular processes, Ann N Y Acad Sci, 726, 281, 10.1111/j.1749-6632.1994.tb52829.x Cornwell, 1987, ATP-binding properties of P glycoprotein from multidrug-resistant KB cells, FASEB J, 1, 51, 10.1096/fasebj.1.1.2886389 Scheffer, 1995, The drug resistance-related protein LRP is the human major vault protein, Nat Med, 1, 578, 10.1038/nm0695-578 Komlodi-Pasztor, 2011, Mitosis is not a key target of microtubule agents in patient tumors, Nat Rev Clin Oncol, 10.1038/nrclinonc.2010.228 Gleeson, 2011, Probing the links between in vitro potency, ADMET and physicochemical parameters, Nat Rev Drug Discov, 10, 197, 10.1038/nrd3367 Shoemaker, 2006, The NCI60 human tumour cell line anticancer drug screen, Nat Rev Cancer, 6, 813, 10.1038/nrc1951 De Graaf, 1993, Changes in glycosylation of L1210 cells after exposure to various antimetabolites, Eur J Cancer, 29A, 1760, 10.1016/0959-8049(93)90120-5 Pels Rijcken, 1989, Incorporation of 5-fluorouracil into nucleotide sugars and the effect on glycoconjugates in rat hepatoma cells and hepatocytes, Adv Exp Med Biol, 253B, 313, 10.1007/978-1-4684-5676-9_46 Lowe, 2010, Network biology as a new approach to drug discovery, Curr Opin Drug Discov Devel, 13, 524 Borg, 2004, Novel mode of action of c-kit tyrosine kinase inhibitors leading to NK cell-dependent antitumor effects, J Clin Invest, 114, 379, 10.1172/JCI21102 Menard, 2009, Natural killer cell IFN-gamma levels predict long-term survival with imatinib mesylate therapy in gastrointestinal stromal tumor-bearing patients, Cancer Res, 69, 3563, 10.1158/0008-5472.CAN-08-3807 Lee, 2009, Exploiting the promiscuity of imatinib, J Biol, 8, 30, 10.1186/jbiol134 Jimeno, 2006, Multitargeted therapy: can promiscuity be praised in an era of political correctness?, Crit Rev Oncol Hematol, 59, 150, 10.1016/j.critrevonc.2006.01.005 Larkin, 2006, Kinase inhibitors in the treatment of renal cell carcinoma, Crit Rev Oncol Hematol, 60, 216, 10.1016/j.critrevonc.2006.06.008 Diasio, 1988, Familial deficiency of dihydropyrimidine dehydrogenase. Biochemical basis for familial pyrimidinemia and severe 5-fluorouracil-induced toxicity, J Clin Invest, 81, 47, 10.1172/JCI113308 Egorin, 1984, Pharmacokinetics and dosage reduction of cis-diammine(1,1-cyclobutanedicarboxylato)platinum in patients with impaired renal function, Cancer Res, 44, 5432 Mathijssen, 2001, Clinical pharmacokinetics and metabolism of irinotecan (CPT-11), Clin Cancer Res, 7, 2182 Zhou, 2006, Clinical pharmacogenomics of thiopurine S-methyltransferase, Curr Clin Pharmacol, 1, 119, 10.2174/157488406784111627 Ng, 2012, Dosing modifications of targeted cancer therapies in patients with special needs: evidence and controversies, Crit Rev Oncol Hematol, 81, 58 Delbaldo, 2006, Pharmacokinetic–pharmacodynamic relationships of imatinib and its main metabolite in patients with advanced gastrointestinal stromal tumors, Clin Cancer Res, 12, 6073, 10.1158/1078-0432.CCR-05-2596 Gambacorti-Passerini, 2003, Alpha1 acid glycoprotein binds to imatinib (STI571) and substantially alters its pharmacokinetics in chronic myeloid leukemia patients, Clin Cancer Res, 9, 625 Widmer, 2006, Population pharmacokinetics of imatinib and the role of alpha-acid glycoprotein, Br J Clin Pharmacol, 62, 97, 10.1111/j.1365-2125.2006.02719.x Lynch, 2004, Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib, N Engl J Med, 350, 2129, 10.1056/NEJMoa040938 Fukuoka, 2003, Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial) [corrected], J Clin Oncol, 21, 2237, 10.1200/JCO.2003.10.038 Giaccone, 2004, Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial—INTACT 1, J Clin Oncol, 22, 777, 10.1200/JCO.2004.08.001 Herbst, 2004, Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial—INTACT 2, J Clin Oncol, 22, 785, 10.1200/JCO.2004.07.215 Albanell, 2002, Pharmacodynamic studies of the epidermal growth factor receptor inhibitor ZD1839 in skin from cancer patients: histopathologic and molecular consequences of receptor inhibition, J Clin Oncol, 20, 110, 10.1200/JCO.20.1.110 Kimmelman, 2011, Predicting harms and benefits in translational trials: ethics, evidence, and uncertainty, PLoS Med, 8, e1001010, 10.1371/journal.pmed.1001010 Muggia, 2009, XIII International Charles Heidelberger Symposium and 50 years of fluoropyrimidines in cancer therapy held on September 6 to 8, 2007 at New York University Cancer Institute, Smilow Conference Center, Mol Cancer Ther, 8, 992, 10.1158/1535-7163.MCT-08-0731 Field, 1963, 5-Fluorouracil (Nsc-19893) treatment of advanced cancer in ambulatory patients, Cancer Chemother Rep, 33, 45 Sharp, 1962, 5-Fluorouracil in the treatment of inoperable carcinoma of the colon and rectum, Cancer Chemother Rep, 20, 97 Diasio, 1989, Clinical pharmacology of 5-fluorouracil, Clin Pharmacokinet, 16, 215, 10.2165/00003088-198916040-00002 Chirstophidis, 1978, Fluorouracil therapy in patients with carcinoma of the large bowel: a pharmacokinetic comparison of various rates and routes of administration, Clin Pharmacokinet, 3, 330, 10.2165/00003088-197803040-00006 Ramirez, 1969, Comparative study of monthly courses versus weekly doses of 5-fluorouracil (NSC-19893), Cancer Chemother Rep, 53, 243 1998, Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer, J Clin Oncol, 16, 301, 10.1200/JCO.1998.16.1.301 Harris, 1990, Relationship between dihydropyrimidine dehydrogenase activity and plasma 5-fluorouracil levels with evidence for circadian variation of enzyme activity and plasma drug levels in cancer patients receiving 5-fluorouracil by protracted continuous infusion, Cancer Res, 50, 197 Seifert, 1975, Comparison of continuously infused 5-fluorouracil with bolus injection in treatment of patients with colorectal adenocarcinoma, Cancer, 36, 123, 10.1002/1097-0142(197507)36:1<123::AID-CNCR2820360108>3.0.CO;2-C Shah, 1985, 5-FU infusion in advanced colorectal cancer: a comparison of three dose schedules, Cancer Treat Rep, 69, 739 Park, 1988, Enhancement of fluorinated pyrimidine-induced cytotoxicity by leucovorin in human colorectal carcinoma cell lines, J Natl Cancer Inst, 80, 1560, 10.1093/jnci/80.19.1560 1992, Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: evidence in terms of response rate, J Clin Oncol, 10, 896, 10.1200/JCO.1992.10.6.896 Andre, 2004, Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer, N Engl J Med, 350, 2343, 10.1056/NEJMoa032709 Douillard, 2000, Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial, Lancet, 355, 1041, 10.1016/S0140-6736(00)02034-1 Kohne, 2005, Phase III study of weekly high-dose infusional fluorouracil plus folinic acid with or without irinotecan in patients with metastatic colorectal cancer: European Organisation for Research and Treatment of Cancer Gastrointestinal Group Study 40986, J Clin Oncol, 23, 4856, 10.1200/JCO.2005.05.546 Kuebler, 2007, Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07, J Clin Oncol, 25, 2198, 10.1200/JCO.2006.08.2974 Demicheli, 2010, Recurrence and mortality dynamics for breast cancer patients undergoing mastectomy according to estrogen receptor status: different mortality but similar recurrence, Cancer Sci, 101, 826, 10.1111/j.1349-7006.2009.01472.x Demicheli, 2007, Tumor dormancy and surgery-driven interruption of dormancy in breast cancer: learning from failures, Nat Clin Pract Oncol, 4, 699, 10.1038/ncponc0999 Stein, 2008, Tumor growth rates derived from data for patients in a clinical trial correlate strongly with patient survival: a novel strategy for evaluation of clinical trial data, Oncologist, 13, 1046, 10.1634/theoncologist.2008-0075 Stein, 2011, Tumor regression and growth rates determined in five intramural NCI prostate cancer trials: the growth rate constant as an indicator of therapeutic efficacy, Clin Cancer Res, 17, 907, 10.1158/1078-0432.CCR-10-1762 Stein, 2008, Bevacizumab reduces the growth rate constants of renal carcinomas: a novel algorithm suggests early discontinuation of bevacizumab resulted in a lack of survival advantage, Oncologist, 13, 1055, 10.1634/theoncologist.2008-0016 Frei, 1980, Dose: a critical factor in cancer chemotherapy, Am J Med, 69, 585, 10.1016/0002-9343(80)90472-6 Hryniuk, 1988, More is better, J Clin Oncol, 6, 1365, 10.1200/JCO.1988.6.9.1365 Pasquier, 2010, Metronomic chemotherapy: new rationale for new directions, Nat Rev Clin Oncol, 7, 455, 10.1038/nrclinonc.2010.82 Gatenby, 2009, Adaptive therapy, Cancer Res, 69, 4894, 10.1158/0008-5472.CAN-08-3658 Penel, 2011, Cyclophosphamide-based metronomic chemotherapy: after 10 years of experience, where do we stand and where are we going?, Crit Rev Oncol Hematol Ocana, 2011, When are “positive” clinical trials in oncology truly positive?, J Natl Cancer Inst, 103, 16, 10.1093/jnci/djq463 Feinstein, 1995, Meta-analysis: statistical alchemy for the 21st century, J Clin Epidemiol, 48, 71, 10.1016/0895-4356(94)00110-C Fojo, 2010, Biologically targeted cancer therapy and marginal benefits: are we making too much of too little or are we achieving too little by giving too much?, Clin Cancer Res, 16, 5972, 10.1158/1078-0432.CCR-10-1277 Booth, 2010, Evaluating patient-centered outcomes in the randomized controlled trial and beyond: informing the future with lessons from the past, Clin Cancer Res, 16, 5963, 10.1158/1078-0432.CCR-10-1962 Seruga, 2010, Absolute benefits of medical therapies in phase III clinical trials for breast and colorectal cancer, Ann Oncol, 21, 1411, 10.1093/annonc/mdp552 Demicheli, 2010, Gene regulatory networks: a new conceptual framework to analyse breast cancer behaviour, Ann Oncol Goss, 2010, Does tumour dormancy offer a therapeutic target?, Nat Rev Cancer, 10, 871, 10.1038/nrc2933 Schipper, 1995, Shifting the cancer paradigm: must we kill to cure?, J Clin Oncol, 13, 801, 10.1200/JCO.1995.13.4.801 Ruggiero, 2006, The biological sense of cancer: a hypothesis, Theor Biol Med Model, 3, 43, 10.1186/1742-4682-3-43 Diop-Frimpong, 2011, Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors, Proc Natl Acad Sci U S A, 108, 2909, 10.1073/pnas.1018892108 Jain, 2010, Delivering nanomedicine to solid tumors, Nat Rev Clin Oncol, 7, 653, 10.1038/nrclinonc.2010.139