Clinical, pharmacokinetic and pharmacodynamic evaluations of metronomic UFT and cyclophosphamide plus celecoxib in patients with advanced refractory gastrointestinal cancers

Angiogenesis

Volumn 15, Issue 2, 2012, Pages 275-286

  Allegrini, Giacomo ^a   Di Desidero, Teresa ^b   Barletta, Maria Teresa ^b   Fioravanti, Anna ^b   Orlandi, Paola ^b   Canu, Bastianina ^b   Chericoni, Silvio ^b   Loupakis, Fotios ^b   Di Paolo, Antonello ^b   Masi, Gianluca ^b   Fontana, Andrea ^b   Lucchesi, Sara ^a,b   Arrighi, Giada ^a   Giusiani, Mario ^b   Ciarlo, Andrea ^c   Brandi, Giovanni ^d   Danesi, Romano ^b   Kerbel, Robert S ^e   Falcone, Alfredo ^b   Bocci, Guido ^b  

^a Division of Medical Oncology   (Italy)

^b UNIVERSITY OF PISA   (Italy)

^c UO Oncologia Medica Az USL4   (Italy)

^d UNIVERSITY OF BOLOGNA   (Italy)

^e UNIVERSITY OF TORONTO   (Canada)

Author keywords

Angiogenesis; Cyclophosphamide; Gastrointestinal cancer patients; GHB; Metronomic chemotherapy; Pharmacodynamic biomarkers; Pharmacokinetics; UFT

Indexed keywords

4 HYDROXYBUTYRIC ACID; CELECOXIB; CYCLOPHOSPHAMIDE; DIHYDROFLUOROURACIL; FLUOROURACIL; TEGAFUR; THROMBOSPONDIN 1; UFT; URACIL; VASCULAR ENDOTHELIAL CADHERIN; VASCULOTROPIN; ANTINEOPLASTIC AGENT; PYRAZOLE DERIVATIVE; SULFONAMIDE; VASCULOTROPIN A;

ADULT; AGED; AREA UNDER THE CURVE; ARTICLE; BLOOD TOXICITY; CD133 GENE; CLINICAL ARTICLE; CONTROLLED STUDY; CORRELATION ANALYSIS; DIARRHEA; DIGESTIVE SYSTEM CANCER; DISEASE DURATION; DRUG RESPONSE; DRUG TOLERABILITY; GENE; GENE EXPRESSION; HUMAN; MALE; MAXIMUM PLASMA CONCENTRATION; NAUSEA; OVERALL SURVIVAL; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEIN BLOOD LEVEL; UNSPECIFIED SIDE EFFECT; BLOOD; FEMALE; GASTROINTESTINAL TUMOR; MIDDLE AGED;

AGED; AGED, 80 AND OVER; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CYCLOPHOSPHAMIDE; FEMALE; GASTROINTESTINAL NEOPLASMS; HUMANS; MALE; MIDDLE AGED; PYRAZOLES; SULFONAMIDES; TEGAFUR; URACIL; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84865111710     PISSN: 09696970     EISSN: 15737209     Source Type: Journal    
DOI: 10.1007/s10456-012-9260-6     Document Type: Article

References (53)

1. Kerbel RS, Kamen BA (2004) The anti-angiogenic basis of metronomic chemotherapy. Nat Rev Cancer 4(6):423-436 (Pubitemid 38745528)
2. Bocci G, Tuccori M, Emmenegger U, Liguori V, Falcone A, Kerbel RS, Del Tacca M (2005) Cyclophosphamide-methotrexate 'metronomic' chemotherapy for the palliative treatment of metastatic breast cancer. A comparative pharmacoeconomic evaluation. Ann Oncol 16(8):1243-1252 (Pubitemid 41166506)
3. Fioravanti A, Canu B, Ali G, Orlandi P, Allegrini G, Di Desidero T, Emmenegger U, Fontanini G, Danesi R, Del Tacca M, Falcone A, Bocci G (2009) Metronomic 5-fluorouracil, oxaliplatin and irinotecan in colorectal cancer. Eur J Pharmacol 619(1-3):8-14
4. Rapisarda A, Zalek J, Hollingshead M, Braunschweig T, Uranchimeg B, Bonomi CA, Borgel SD, Carter JP, Hewitt SM, Shoemaker RH, Melillo G (2004) Schedule-dependent inhibition of hypoxia-inducible factor-1 protein accumulation, angiogenesis, and tumor growth by topotecan in U251-HRE glioblastoma xenografts. Cancer Res 64(19):6845-6848 (Pubitemid 39330988)
5. Lee K, Qian DZ, Rey S, Wei H, Liu JO, Semenza GL (2009) Anthracycline chemotherapy inhibits HIF-1 transcriptional activity and tumor-induced mobilization of circulating angiogenic cells. Proc Natl Acad Sci 106(7):2353-2358
6. Penel N, Adenis A, Bocci G (2011) Cyclophosphamide-based metronomic chemotherapy: after 10 years of experience, where do we stand and where are we going? Crit Rev Oncol Hematol. Jun 2. doi:10.1016/j.critrevonc.2011.04.009
7. Allegrini G, Falcone A, Fioravanti A, Barletta MT, Orlandi P, Loupakis F, Cerri E, Masi G, Di Paolo A, Kerbel RS, Danesi R, Del Tacca M, Bocci G (2008) A pharmacokinetic and pharmacodynamic study on metronomic irinotecan in metastatic colorectal cancer patients. Br J Cancer 98(8):1312-1319 (Pubitemid 351543577)
8. Browder T, Butterfield CE, Kraling BM, Shi B, Marshall B, O'Reilly MS, Folkman J (2000) Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drugresistant cancer. Cancer Res 60(7):1878-1886 (Pubitemid 30207647)
9. Blansfield JA, Caragacianu D, Alexander HR III, Tangrea MA, Morita SY, Lorang D, Schafer P, Muller G, Stirling D, Royal RE, Libutti SK (2008) Combining agents that target the tumor microenvironment improves the efficacy of anticancer therapy. Clin Cancer Res 14(1):270-280 (Pubitemid 351384377)
10. Young SD, Whissell M, Noble JC, Cano PO, Lopez PG, Germond CJ (2006) Phase II clinical trial results involving treatment with low-dose daily oral cyclophosphamide, weekly vinblastine, and rofecoxib in patients with advanced solid tumors. Clin Cancer Res 12(10):3092-3098 (Pubitemid 43837356)
11. Leahy KM, Ornberg RL, Wang Y, Zweifel BS, Koki AT, Masferrer JL (2002) Cyclooxygenase-2 inhibition by celecoxib reduces proliferation and induces apoptosis in angiogenic endothelial cells in vivo. Cancer Res 62(3):625-631 (Pubitemid 34126930)
12. Wu YL, Fu SL, Zhang YP, Qiao MM, Chen Y (2005) Cyclooxygenase-2 inhibitors suppress angiogenesis and growth of gastric cancer xenografts. Biomed Pharmacother 59(Suppl 2):S289-S292
13. Tanaka F (2007) UFT (tegafur and uracil) as postoperative adjuvant chemotherapy for solid tumors (carcinoma of the lung, stomach, colon/rectum, and breast): clinical evidence, mechanism of action, and future direction. Surg Today 37(11):923-943 (Pubitemid 47622216)
14. Bennouna J, Saunders M, Douillard JY (2009) The role of UFT in metastatic colorectal cancer. Oncology 76(5):301-310
15. Nakayama T, Noguchi S (2010) Therapeutic usefulness of postoperative adjuvant chemotherapy with Tegafur-Uracil (UFT) in patients with breast cancer: focus on the results of clinical studies in Japan. Oncologist 15(1):26-36
16. Kato H, Ichinose Y, Ohta M, Hata E, Tsubota N, Tada H, Watanabe Y, Wada H, Tsuboi M, Hamajima N (2004) A randomized trial of adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung. N Engl J Med 350(17):1713-1721 (Pubitemid 38501140)
17. Watanabe T, Sano M, Takashima S, Kitaya T, Tokuda Y, Yoshimoto M, Kohno N, Nakagami K, Iwata H, Shimozuma K, Sonoo H, Tsuda H, Sakamoto G, Ohashi Y (2009) Oral uracil and tegafur compared with classic cyclophosphamide, methotrexate, Fluorouracil as postoperative chemotherapy in patients with nodenegative, high-risk breast cancer: National Surgical Adjuvant Study for breast cancer 01 trial. J Clin Oncol 27(9):1368-1374
18. Basaki Y, Chikahisa L, Aoyagi K, Miyadera K, Yonekura K, Hashimoto A, Okabe S, Wierzba K, Yamada Y (2001) Gammahydroxybutyric acid and 5-fluorouracil, metabolites of UFT, inhibit the angiogenesis induced by vascular endothelial growth factor. Angiogenesis 4(3):163-173 (Pubitemid 34174305)
19. Munoz R, Man S, Shaked Y, Lee CR, Wong J, Francia G, Kerbel RS (2006) Highly efficacious nontoxic preclinical treatment for advanced metastatic breast cancer using combination oral UFTcyclophosphamide metronomic chemotherapy. Cancer Res 66(7):3386-3391
20. Nio Y, Iguchi C, Kodama H, Itakura M, Hashimoto K, Koike M, Toga T, Maruyama R, Fukushima M (2007) Cyclophosphamide augments the anti-tumor efficacy of uracil and tegafur by inhibiting dihydropyrimidine dehydrogenase. Oncol Rep 17(1):153-159
21. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3):205-216
22. Wu AT, Au JL, Sadee W (1978) Hydroxylated metabolies of R, S-1-(tetrahydro-2-furanyl)-5-fluorouracil (Ftorafur) in rats and rabbits. Cancer Res 38(1):210-214 (Pubitemid 8253539)
23. Bocci G, Barbara C, Vannozzi F, Di Paolo A, Melosi A, Barsanti G, Allegrini G, Falcone A, Del Tacca M, Danesi R (2006) A pharmacokinetic-based test to prevent severe 5-fluorouracil toxicity. Clin Pharmacol Ther 80(4):384-395 (Pubitemid 44479748)
24. Villain M, Cirimele V, Ludes B, Kintz P (2003) Ultra-rapid procedure to test for gamma-hydroxybutyric acid in blood and urine by gas chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 792(1):83-87 (Pubitemid 36773804)
25. Bocci G, Fioravanti A, Orlandi P, Bernardini N, Collecchi P, Del Tacca M, Danesi R (2005) Fluvastatin synergistically enhances the antiproliferative effect of gemcitabine in human pancreatic cancer MIAPaCa-2 cells. Br J Cancer 93(3):319-330 (Pubitemid 43080034)
26. ScartozziM, Falcone A, Pucci F, Braconi C, Pierantoni C, Cavanna L, Franciosi V, Berardi R, Beretta G,Masi G, Allegrini G, Zaniboni A, Labianca R, Cascinu S (2006) Capecitabine and mitomycin C may be an effective treatment option for third-line chemotherapy in advanced colorectal cancer. Tumori 92(5):384-388 (Pubitemid 44861772)
27. Chen HX, Mooney M, Boron M, Vena D, Mosby K, Grochow L, Jaffe C, Rubinstein L, Zwiebel J, Kaplan RS (2006) Phase II multicenter trial of bevacizumab plus fluorouracil and leucovorin in patients with advanced refractory colorectal cancer: an NCI Treatment Referral Center Trial TRC-0301. J Clin Oncol 24(21):3354-3360 (Pubitemid 46638889)
28. McCollum AD, Wu B, Clark JW, Kulke MH, Enzinger PC, Ryan DP, Earle CC, Michelini A, Fuchs CS (2006) The combination of capecitabine and thalidomide in previously treated, refractory metastatic colorectal cancer. Am J Clin Oncol 29(1):40-44 (Pubitemid 44356713)
29. Glode LM, Barqawi A, Crighton F, Crawford ED, Kerbel R (2003) Metronomic therapy with cyclophosphamide and dexamethasone for prostate carcinoma. Cancer 98(8):1643-1648 (Pubitemid 37238620)
30. Fontana A, Galli L, Fioravanti A, Orlandi P, Galli C, Landi L, Bursi S, Allegrini G, Fontana E, Di Marsico R, Antonuzzo A, D'Arcangelo M, Danesi R, Del Tacca M, Falcone A, Bocci G (2009) Clinical and pharmacodynamic evaluation of metronomic cyclophosphamide, celecoxib, and dexamethasone in advanced hormone-refractory prostate cancer. Clin Cancer Res 15(15): 4954-4962
31. Colleoni M, Orlando L, Sanna G, Rocca A, Maisonneuve P, Peruzzotti G, Ghisini R, Sandri MT, Zorzino L, Nole F, Viale G, Goldhirsch A (2006) Metronomic low-dose oral cyclophosphamide and methotrexate plus or minus thalidomide in metastatic breast cancer: antitumor activity and biological effects. Ann Oncol 17(2):232-238 (Pubitemid 43160111)
32. Dellapasqua S, Bertolini F, Bagnardi V, Campagnoli E, Scarano E, Torrisi R, Shaked Y, Mancuso P, Goldhirsch A, Rocca A, Pietri E, Colleoni M (2008) Metronomic cyclophosphamide and capecitabine combined with bevacizumab in advanced breast cancer. J Clin Oncol 26(30):4899-4905
33. Garcia-Saenz JA, Martin M, Calles A, Bueno C, Rodriguez L, Bobokova J, Custodio A, Casado A, Diaz-Rubio E (2008) Bevacizumab in combination with metronomic chemotherapy in patients with anthracycline-and taxane-refractory breast cancer.J Chemother 20(5):632-639
34. Lin EH, Curley SA, Crane CC, Feig B, Skibber J, Delcos M, Vadhan SR, Morris J, Ayers GD, Ross A, Brown T, Rodriguez-Bigas MA, Janjan N (2006) Retrospective study of capecitabine and celecoxib in metastatic colorectal cancer: potential benefits and COX-2 as the common mediator in pain, toxicities and survival? Am J Clin Oncol 29(3):232-239 (Pubitemid 44270930)
35. Penel N, Clisant S, Dansin E, Desauw C, Degardin M, Mortier L, Vanhuyse M, Bonodeau F, Fournier C, Cazin JL, Adenis A (2010) Megestrol acetate versus metronomic cyclophosphamide in patients having exhausted all effective therapies under standard care. Br J Cancer 102(8):1207-1212
36. Hoff PM (2000) The tegafur-based dihydropyrimidine dehydrogenase inhibitory fluoropyrimidines, UFT/leucovorin (ORZEL) and S-1: a review of their clinical development and therapeutic potential. Invest New Drugs 18(4):331-342
37. Shirao K, Hoff PM, Ohtsu A, Loehrer PJ, Hyodo I, Wadler S, Wadleigh RG, O'Dwyer PJ, Muro K, Yamada Y, Boku N, Nagashima F, Abbruzzese JL (2004) Comparison of the efficacy, toxicity, and pharmacokinetics of a uracil/tegafur (UFT) plus oral leucovorin (LV) regimen between Japanese and American patients with advanced colorectal cancer: joint United States and Japan study of UFT/LV. J Clin Oncol 22(17):3466-3474 (Pubitemid 41103652)
38. Tang TC, Man S, Lee CR, Xu P, Kerbel RS (2010) Impact of metronomic UFT/cyclophosphamide chemotherapy and antiangiogenic drug assessed in a new preclinical model of locally advanced orthotopic hepatocellular carcinoma. Neoplasia 12(3):264-274
39. Ogawa Y, Ishikawa T, Chung SH, Ikeda K, Takashima T, Onoda N, Nakata B, Nishiguchi Y, Hirakawa K (2003) Oral UFT and cyclophosphamide combination chemotherapy for metastatic breast cancer. Anticancer Res 23(4):3453-3457 (Pubitemid 36975448)
40. Zweig MH, Campbell G (1993) Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem 39(4):561-577 (Pubitemid 23118304)
41. Bocci G, Danesi R, Di Paolo AD, Innocenti F, Allegrini G, Falcone A, Melosi A, Battistoni M, Barsanti G, Conte PF, Del Tacca M (2000) Comparative pharmacokinetic analysis of 5-fluorouracil and its major metabolite 5-fluoro-5,6-dihydrouracil after conventional and reduced test dose in cancer patients. Clin Cancer Res 6(8):3032-3037 (Pubitemid 30637725)
42. Yonekura K, Basaki Y, Chikahisa L, Okabe S, Hashimoto A, Miyadera K, Wierzba K, Yamada Y (1999) UFT and its metabolites inhibit the angiogenesis induced by murine renal cell carcinoma, as determined by a dorsal air sac assay in mice. Clin Cancer Res 5(8):2185-2191 (Pubitemid 29399276)
43. Basaki Y, Yonekura K, Chikahisa L, Okabe S, Hashimoto A, Miyadera K, Aoyagi K, Yamada Y (2000) Anti-angiogenic activities of UFT and its metabolites, GHB and GBL, in the dorsal air sac (DAS) model in mice. Gan To Kagaku Ryoho 27(1):93-98
44. Emi Y, Sumiyoshi Y, Oki E, Kakeji Y, Fukui Y, Maehara Y (2007) Pharmacokinetics of gamma-hydroxybutylic acid (GHB) and gamma-butyrolactone (GBL), the anti-angiogenic metabolites of oral fluoropyrimidine UFT, in patients with gastric cancer. Fukuoka Igaku Zasshi 98(12):418-424
45. Kania G, Corbeil D, Fuchs J, Tarasov KV, Blyszczuk P, Huttner WB, Boheler KR, Wobus AM (2005) Somatic stem cell marker prominin-1/CD133 is expressed in embryonic stem cell-derived progenitors. Stem Cells 23(6):791-804 (Pubitemid 40791794)
46. Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De Maria R (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445(7123):111-115 (Pubitemid 46067311)
47. O'Brien CA, Pollett A, Gallinger S, Dick JE (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445(7123):106-110 (Pubitemid 46067310)
48. Bertolini F, Paul S, Mancuso P, Monestiroli S, Gobbi A, Shaked Y, Kerbel RS (2003) Maximum tolerable dose and low-dose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells. Cancer Res 63(15):4342-4346 (Pubitemid 36951001)
49. Shaked Y, Emmenegger U, Man S, Cervi D, Bertolini F, Ben-David Y, Kerbel RS (2005) Optimal biologic dose of metronomic chemotherapy regimens is associated with maximum antiangiogenic activity. Blood 106(9):3058-3061 (Pubitemid 41565900)
50. Dallas NA, Xia L, Fan F, Gray MJ, Gaur P, van Buren G, Samuel S II, Kim MP, Lim SJ, Ellis LM (2009) Chemoresistant colorectal cancer cells, the cancer stem cell phenotype, and increased sensitivity to insulin-like growth factor-I receptor inhibition. Cancer Res 69(5):1951-1957
51. Dejana E, Orsenigo F, Lampugnani MG (2008) The role of adherens junctions and VE-cadherin in the control of vascular permeability. J Cell Sci 121(Pt 13):2115-2122
52. Rabascio C, Muratori E, Mancuso P, Calleri A, Raia V, Foutz T, Cinieri S, Veronesi G, Pruneri G, Lampertico P, Iavarone M, Martinelli G, Goldhirsch A, Bertolini F (2004) Assessing tumor angiogenesis: increased circulating VE-cadherin RNA in patients with cancer indicates viability of circulating endothelial cells. Cancer Res 64(12):4373-4377 (Pubitemid 38802446)
53. Bocci G, Francia G, Man S, Lawler J, Kerbel RS (2003) Thrombospondin 1, a mediator of the antiangiogenic effects of low-dose metronomic chemotherapy. Proc Natl Acad Sci USA 100(22):12917-12922 (Pubitemid 37340000)