Combined modality therapy of gemcitabine and radiation

Oncologist

Volumn 10, Issue 1, 2005, Pages 34-51

  Pauwels, Bea ^a   Korst, Annelies E C ^a   Lardon, Filip ^a   Vermorken, Jan B ^a  

^a UNIVERSITY OF ANTWERP   (Belgium)

Author keywords

Clinic; Gemcitabine; In vitro; In vivo; Radiosensitization; Radiotherapy

Indexed keywords

CISPLATIN; CYTARABINE; DEOXYCYTIDINE KINASE; FLUOROURACIL; GEMCITABINE; MITOMYCIN C; PACLITAXEL;

APOPTOSIS; BILIARY TRACT TUMOR; BLADDER TUMOR; BREAST TUMOR; CANCER RADIOTHERAPY; CELLULAR DISTRIBUTION; CLINICAL TRIAL; CYTOTOXICITY; DIGESTIVE SYSTEM FISTULA; DIGESTIVE SYSTEM ULCER; DNA SYNTHESIS; DRUG MEGADOSE; ENZYME ACTIVITY; GASTROINTESTINAL HEMORRHAGE; GERM CELL TUMOR; HEAD AND NECK CANCER; HUMAN; IN VITRO STUDY; LUNG NON SMALL CELL CANCER; MEMBRANE TRANSPORT; MULTIMODALITY CANCER THERAPY; OVARY TUMOR; PANCREAS CANCER; PANCREAS TUMOR; PRIORITY JOURNAL; RADIOSENSITIZATION; REVIEW; UTERINE CERVIX CANCER;

ANIMALS; ANTIMETABOLITES, ANTINEOPLASTIC; APOPTOSIS; CELL CYCLE; CLINICAL TRIALS; COMBINED MODALITY THERAPY; DEOXYCYTIDINE; DNA; DNA DAMAGE; DNA REPAIR; HUMANS; NEOPLASMS; RADIATION-SENSITIZING AGENTS; RODENTIA; TUMOR CELLS, CULTURED;

EID: 12844287650     PISSN: 10837159     EISSN: None     Source Type: Journal    
DOI: 10.1634/theoncologist.10-1-34     Document Type: Review

References (122)

1. Suit HD. Potential for improving survival rates for the cancer patient by increasing the efficacy of treatment of the primary lesion. Cancer 1982;50:1227-1234.
2. Intensity Modulated Radiation Therapy Collaborative Working Group. Intensity-modulated radiotherapy: current status and issues of interest. Int J Radiat Oncol Biol Phys 2001;51:880-914.
3. Beck Bornholdt HP, Dubben HH, Liertz Petersen C et al. Hyperfractionation: where do we stand? Radiother Oncol 1997;43:1-21.
4. Zelefsky MJ, Leibel SA, Kutcher GI et al. Three-dimensional conformal radiotherapy and dose escalation: where do we stand? Semin Radiat Oncol 1998;8:107-114.
5. Hennequin C, Favaudon V, Balosso J et al. Associations radio-chimiotherapies: de la biologie a la clinique. [Radiochemotherapy combinations: from biology to clinics]. Bull Cancer 1994;81:1005-1013.
6. Gordon AT, McMillan TJ. A role for molecular radiobiology in radiotherapy? Clin Oncol (R Coll Radiol) 1997;9:70-78.
7. Doyle TH, Mornex F, McKenna G. The clinical implications of gemcitabine radiosensitization. Clin Cancer Res 2001;7:226-228.
8. Anderson H, Hopwood P, Stephens RJ et al. Gemcitabine plus best supportive care (BSC) vs BSC in inoperable non-small cell lung cancer - a randomized trial with quality of life as the primary outcome. UK NSCLC Gemcitabine Group. Non-Small Cell Lung Cancer. Br J Cancer 2000;83:447-453.
9. Burris HA 3rd, Moore MJ, Andersen J et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 1997;15:2403-2413.
10. Lorusso V, Pollera CF, Antimi M et al. A phase II study of gemcitabine in patients with transitional cell carcinoma of the urinary tract previously treated with platinum. Italian Co-operative Group on Bladder Cancer. Eur J Cancer 1998;34:1208-1212.
11. Spielmann M, Llombart Cussac A, Kalla S et al. Single-agent gemcitabine is active in previously treated metastatic breast cancer. Oncology 2001;60:303-307.
12. Lund B, Hansen OP, Neij JP et al. Phase II study of gemcitabine (2′,2′-difluorodeoxycytidine) in previously treated ovarian cancer patients. J Natl Cancer Inst 1994;86:1530-1533.
13. Einhorn LH, Stender MJ, Williams SD. Phase II trial of gemcitabine in refractory germ cell tumors. J Clin Oncol 1999;17:509-511.
14. Cormier Y, Eisenhauer E, Muldal A et al. Gemcitabine is an active new agent in previously untreated extensive small cell lung cancer (SCLC). A study of the National Cancer Institute of Canada Clinical Trials Group. Ann Oncol 1994;5:283-285.
15. Kubicka S, Rudolph KL, Tietze MK et al. Phase II study of systemic gemcitabine chemotherapy for advanced unresectable hepatobiliary carcinomas. Hepatogastroenterology 2001;48:783-789.
16. Catimel G, Vermorken JB, Clavel M et al. A phase II study of Gemcitabine (LY 188011) in patients with advanced squamous cell carcinoma of the head and neck. EORTC Early Clinical Trials Group. Ann Oncol 1994;5:543-547.
17. Mutch DG, Bloss JD. Gemcitabine in cervical cancer. Gynecol Oncol 2003;90:S8-S15.
18. Dumontet C, Morschhauser F, Solal-Celigny P et al. Gemcitabine as a single agent in the treatment of relapsed or refractory low-grade non-Hodgkin's lymphoma. Br J Haematol 2001;113:772-778.
19. Sallah S, Wan JY, Nguyen NP. Treatment of refractory T-cell malignancies using gemcitabine. Br J Haematol 2001;113:185-187.
20. Hertel LW, Kroin JS, Misner JW et al. Synthesis of 2′-deoxy- 2′,2′-deoxy-2′,2′-difluoro-D-ribofuranosyl nucleosides. J Org Chem 1988;53:2406-2409.
21. Hertel LW, Boder GB, Kroin JS et al. Evaluation of the antitumor activity of gemcitabine (2′,2′-difluoro-2′-deoxycytidine). Cancer Res 1990;50:4417-4422.
22. Heinemann V, Hertel LW, Grindey GB et al. Comparison of the cellular pharmacokinetics and toxicity of 2′,2′-difluorodeoxycytidine and 1-β-D-arabinofuranosylcytosine. Cancer Res 1988;48:4024-4031.
23. Mackey JR, Mani RS, Selner M et al. Functional nucleoside transporters are required for gemcitabine influx and manifestation of toxicity in cancer cell lines. Cancer Res 1998;58:4349-4357.
24. Lostao MP, Mata JF, Larrayoz IM et al. Electrogenic uptake of nucleosides and nucleoside-derived drugs by the human nucleoside transporter 1 (hCNT1) expressed in Xenopus laevis oocytes. FEBS Lett 2000;481:137-140.
25. Mackey JR, Yao SY, Smith KM et al. Gemcitabine transport in xenopus oocytes expressing recombinant plasma membrane mammalian nucleoside transporters. J Natl Cancer Inst 1999;91:1876-1881.
26. +-dependent nucleoside transporter (CNT) family: identification and characterization of novel human and mouse proteins (hCNT3 and mCNT3) broadly selective for purine and pyrimidine nucleosides (system cib). Mol Membr Biol 2001;18:65-72.
27. Huang P, Chubb S, Hertel LW et al. Action of 2′,2′- difluorodeoxycytidine on DNA synthesis. Cancer Res 1991;51:6110-6117.
28. Ruiz van Haperen VW, Veerman G, Vermorken JB et al. 2′,2′- Difluoro-deoxycytidine (gemcitabine) incorporation into RNA and DNA of tumour cell lines. Biochem Pharmacol 1993;46:762-766.
29. Ruiz van Haperen VW, Veerman G, Boven E et al. Schedule dependence of sensitivity to 2′,2′-difluorodeoxycytidine (Gemcitabine) in relation to accumulation and retention of its triphosphate in solid tumour cell lines and solid tumours. Biochem Pharmacol 1994;48:1327-1339.
30. van Moorsel CJA, Bergman AM, Veerman G et al. Differential effects of gemcitabine on ribonucleotide pools of twenty-one solid tumour and leukaemia cell lines. Biochim Biophys Acta 2000;1474:5-12.
31. Tolis C, Peters GJ, Ferreira CG et al. Cell cycle disturbances and apoptosis induced by topotecan and gemcitabine on human lung cancer cell lines. Eur J Cancer 1999;35:796-807.
32. Pauwels B, Korst AEC, Pattyn GGO et al. Cell cycle effect of gemcitabine and its role in the radiosensitizing mechanism in vitro. Int J Radiat Oncol Biol Phys 2003;57:1075-1083.
33. Bouffard DY, Momparler RL. Comparison of the induction of apoptosis in human leukemic cell lines by 2′,2′-difluorodeoxycytidine (gemcitabine) and cytosine arabinoside. Leuk Res 1995;19:849-856.
34. Huang P, Plunkett W. Fludarabine- and gemcitabine-induced apoptosis: incorporation of analogs into DNA is a critical event. Cancer Chemother Pharmacol 1995;36:181-188.
35. Ferreira CG, Tolis C, Span SW et al. Drug-induced apoptosis in lung cancer cells is not mediated by the Fas/FasL (CD95/APO1) signaling pathway. Clin Cancer Res 2000;6:203-212.
36. Pourquier P, Gioffre C, Kohlhagen G et al. Gemcitabine (2′,2′-difluoro-2′-deoxycytidine), an antimetabolite that poisons topoisomerase I. Clin Cancer Res 2002;8:2499-2504.
37. Gmeiner WH, Yu SY, Pon RT et al. Structural basis for topoisomerase I inhibition by nucleoside analogs. Nucleosides Nucleotides Nucleic Acids 2003;22:653-658.
38. Peters GJ, van der Wilt CL, van Moorsel CJA et al. Basis for effective combination cancer chemotherapy with antimetabolites. Pharmacol Ther 2000;87:227-253.
39. Heinemann V, Schulz L, Issels RD et al. Gemcitabine: a modulator of intracellular nucleotide and deoxynucleotide metabolism. Semin Oncol 1995;22(suppl 11):11-18.
40. Storniolo AM, Allerheiligen SR, Pearce H. Preclinical, pharmacologic, and phase I studies of gemcitabine. Semin Oncol 1997;24 (suppl 7):2-7.
41. Latz D, Fleckenstein K, Eble M et al. Radiosensitizing potential of gemcitabine (2′,2′-difluoro-2′-deoxycytidine) within the cell cycle in vitro. Int J Radiat Oncol Biol Phys 1998;41:875-882.
42. Bergman AM, Giaccone G, van Moorsel CJ et al. Cross-resistance in the 2′,2′-difluorodeoxycytidine (gemcitabine)-resistant human ovarian cancer cell line AG6000 to standard and investigational drugs. Eur J Cancer 2000;36:1974-1983.
43. Gregoire V, Hittelman WN, Rosier JF et al. Chemo-radiotherapy: Radiosensitizing nucleoside analogues (review). Oncol Rep 1999;6:949-957.
44. Shewach DS, Lawrence TS. Gemcitabine and radiosensitizationin human tumor cells. Invest New Drugs 1996;14:257-263.
45. Pauwels B, Korst AEC, de Pooter CMJ et al. The radiosensitising effect of gemcitabine and the influence of the rescue agent amifostine in vitro. Eur J Cancer 2003;39:838-846.
46. Shewach DS, Hahn TM, Chang E et al. Metabolism of 2′,2′- difluoro-2′-deoxycytidine and radiation sensitization of human colon carcinoma cells. Cancer Res 1994;54:3218-3223.
47. Lawrence TS, Chang EY, Hahn TM et al. Radiosensitization of pancreatic cancer cells by 2′,2′-difluoro-2′-deoxycytidine. Int J Radiat Oncol Biol Phys 1996;34:867-872.
48. Mose S, Karapetian M, Juling Pohlit L et al. The intensification of the radiotherapeutic effect on HeLa-cells by gemcitabine. Strahlen Und Onkol 1999;175:78-83.
49. Mose S, Karapetian M, Juling Pohlit L et al. Radiation enhancement of gemcitabine in two human squamous cell carcinoma cell lines. Anticancer Res 2000;20:401-405.
50. Pacini S, Milano F, Pinzani P et al. Effects of gemcitabine in normal and transformed human lung cell cultures: cytotoxicity and increase in radiation sensitivity. Tumori 1999;85:503-507.
51. Rosier JF, Beauduin M, Bruniaux M et al. The effect of 2′,2′ difluorodeoxycytidine (dFdC, gemcitabine) on radiation-induced cell lethality in two human head and neck squamous carcinoma cell lines differing in intrinsic radiosensitivity. Int J Radiat Biol 1999;75:245-251.
52. Robinson BW, Shewach DS. Radiosensitization by gemcitabine in p53 wild-type and mutant MCF-7 breast carcinoma cell lines. Clin Cancer Res 2001;7:2581-2589.
53. Chen M, Hough AM, Lawrence TS. The role of p53 in gemcitabine-mediated cytotoxicity and radiosensitization. Cancer Chemother Pharmacol 2000;45:369-374.
54. Ostruszka LJ, Shewach DS. The role of cell cycle progression in radiosensitization by 2′,2′-difluoro-2′-deoxycytidine. Cancer Res 2000;60:6080-6088.
55. Lawrence TS, Eisbruch A, Shewach DS. Gemcitabine-mediated radiosensitization. Semin Oncol 1997;24(suppl 7):24-28.
56. Shewach DS, Lawrence TS. Radiosensitization of human solid tumor cell lines with gemcitabine. Semin Oncol 1996;23(suppl 10):65-71.
57. van Bree C, Castro Kreder N, Loves WJ et al. Sensitivity to ionizing radiation and chemotherapeutic agents in gemcitabine-resistant human tumor cell lines. Int J Radiat Oncol Biol Phys 2002;54:237-244.
58. Sangar VK, Cowan R, Margison GP et al. An evaluation of gemcitabines differential radiosensitising effect in related bladder cancer cell lines. Br J Cancer 2004;90:542-548.
59. Mose S, Class R, Weber HW et al. Radiation enhancement by gemcitabine-mediated cell cycle modulations. Am J Clin Oncol 2003;26:60-69.
60. Ferreira CG, Span SW, Peters GJ et al. Chemotherapy triggers apoptosis in a caspase-8-dependent and mitochondria-controlled manner in the non-small cell lung cancer cell line NCI-H460. Cancer Res 2000;60:7133-7141.
61. Lawrence TS, Davis MA, Hough A et al. The role of apoptosis in 2′,2′-difluoro-2′-deoxycytidirne (gemcitabine)-mediated radiosensitization. Clin Cancer Res 2001;7:314-319.
62. Weiss C, Grabenbauer GG, Sauer R et al. Significant increase in residual DNA damage as a possible mechanism of radiosensitization by gemcitabine. Strahlenther Onkol 2003;179:93-98.
63. Gregoire V, Beauduin M, Bruniaux M et al. Radiosensitization of mouse sarcoma cells by fludarabine (F-ara-A) or gemcitabine (dFdC), two nucleoside analogues, is not mediated by an increased induction or a repair inhibition of DNA double-strand breaks as measured by pulsed-field gel electrophoresis. Int J Radiat Biol 1998;73:511-520.
64. Rosier JF, Michaux L, Ameye G et al. The radioenhancement of two human head and neck squamous cell carcinomas by 2′,2′ difluorodeoxycytidine (gemcitabine; dFdC) is mediated by an increase in radiation-induced residual chromosome aberrations but not residual DNA DSBs. Mutat Res 2003;527:15-26.
65. Wachters FM, van Putten JW, Maring JG et al. Selective targeting of homologous DNA recombination repair by gemcitabine. Int J Radiat Oncol Biol Phys 2003;57:553-562.
66. Gregoire V, Rosier JF, De Bast M et al. Role of deoxycytidine kinase (dCK) activity in gemcitabine's radioenhancement in mice and human cell lines in vitro. Radiother Oncol 2002;63:329-338.
67. Fechner G, Perabo FGE, Schmidt DH et al. Preclinical evaluation of a radiosensitizing effect of gemcitabine in p53 mutant and p53 wild type bladder cancer cells. Urology 2003;61:468-473.
68. Yang SJ, Zhang XL, Jiang ML et al. Unusual radiation response of gemcitabine-treated HeLa cells: reduced and enhanced survival. Cancer Lett 2002;187:179-183.
69. Classen J, Paulsen F, Hehr T et al. Effect of gemcitabine on acute and late radiation toxicity of skin and underlying soft tissues to single-dose irradiation in a nude mice model. Int J Radiat Oncol Biol Phys 2002;53:197-205.
70. Gregoire V, Cvilic S, Beauduin M et al. Effect of gemcitabine on the tolerance of the lung to single-dose irradiation in C3H mice. Radiat Res 1999;151:747-749.
71. Mason KA, Milas L, Hunter NR et al. Maximizing therapeutic gain with gemcitabine and fractionated radiation. Int J Radiat Oncol Biol Phys 1999;44:1125-1135.
72. Joschko MA, Webster LK, Groves J et al. Enhancement of radiation-induced regrowth delay by gemcitabine in a human tumor xenograft model. Radiat Oncol Investig 1997;5:62-71.
73. Cividalli A, Livdi E, Ceciarelli F et al. Combined use of gemcitabine and radiation in mice. Anticancer Res 2001;21:307-312.
74. Fields MT, Eisbruch A, Normolle D et al. Radiosensitization produced in vivo by once- versus twice-weekly 2′,2′-difluoro-2′- deoxycytidine (gemcitabine). Int J Radiat Oncol Biol Phys 2000;47:785-791.
75. Milas L, Fujii T, Hunter N et al. Enhancement of tumor radioresponse in vivo by gemcitabine. Cancer Res 1999;59:107-114.
76. Gregoire V, Beauduin M, Rosier JF et al. Kinetics of mouse jejunum radiosensitization by 2′,2′-difluorodeoxycytidine (gemcitabine) and its relationship with pharmacodynamics of DNA synthesis inhibition and cell cycle redistribution in crypt cells. Br J Cancer 1997;76:1315-1321.
77. Blackstock AW, Bernard SA, Richards F et al. Phase I trial of twice-weekly gemcitabine and concurrent radiation in patients with advanced pancreatic cancer. J Clin Oncol 1999;17:2208-2212.
78. Pipas JM, Mitchell SE, Barth RJ et al. Phase I study of twice-weekly gemcitabine and concomitant external-beam radiotherapy in patients with adenocarcinoma of the pancreas. Int J Radiat Oncol Biol Phys 2001;50:1317-1322.
79. Wolff RA, Evans DB, Gravel DM et al. Phase I trial of gemcitabine combined with radiation for the treatment of locally advanced pancreatic adenocarcinoma. Clin Cancer Res 2001;7:2246-2253.
80. Ikeda M, Okada S, Tokuuye K et al. A phase I trial of weekly gemcitabine and concurrent radiotherapy in patients with locally advanced pancreatic cancer. Br J Cancer 2002;86:1551-1554.
81. Cesario A, Margaritora S, Trodella L et al. Incidental surgical findings of a phase I trial of weekly gemcitabine and concurrent radiotherapy in patients with unresectable non-small cell lung cancer. Lung Cancer 2002;37:207-212.
82. van Putten JWG, Price A, van der Leest AH et al. A phase I study of gemcitabine with concurrent radiotherapy in stage III, locally advanced non-small cell lung cancer. Clin Cancer Res 2003;9:2472-2477.
83. McGinn CJ, Zalupski MM, Shureiqi I et al. Phase I trial of radiation dose escalation with concurrent weekly full-dose gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol 2001;19:4202-4208.
84. de Lange SM, van Groeningen CJ, Meijer OWM et al. Gemcitabine- radiotherapy in patients with locally advanced pancreatic cancer. Eur J Cancer 2002;38:1212-1217.
85. Eisbruch A, Shewach DS, Bradford CR et al. Radiation concurrent with gemcitabine for locally advanced head and neck cancer: a phase I trial and intracellular drug incorporation study. J Clin Oncol 2001;19:792-799.
86. Mohiuddin M, Kudrimoti M, Regine WF et al. Concurrent infusional gemcitabine and radiation in the treatment of advanced unresectable GI malignancy: a phase I study. Cancer J 2002;8:255-262.
87. Van Laethem JL, Demols A, Gay F et al. Postoperative adjuvant gemcitabine and concurrent radiation after curative resection of pancreatic head carcinoma: a phase II study. Int J Radiat Oncol Biol Phys 2003;56:974-980.
88. Epelbaum R, Rosenblatt E, Nasrallah S et al. Phase II study of gemcitabine combined with radiation therapy in patients with localized, unresectable pancreatic cancer. J Surg Oncol 2002;81:138-143.
89. Pattaranutaporn P, Thirapakawong C, Chansilpa Y et al. Phase II study of concurrent gemcitabine and radiotherapy in locally advanced stage IIIB cervical carcinoma. Gynecol Oncol 2001;81:404-407.
90. Aguilar-Ponce JL, Granados-Garcia M, Villavicencio V et al. Phase II trial of gemcitabine concurrent with radiation for locally advanced squamous cell carcinoma of the head and neck. Ann Oncol 2004;15:301-306.
91. Li CP, Chao Y, Chi KH et al. Concurrent chemoradiotherapy treatment of locally advanced pancreatic cancer: gemcitabine versus 5-fluorouracil, a randomized controlled study. Int J Radiat Oncol Biol Phys 2003;57:98-104.
92. Attar EC, Ervin T, Janicek M et al. Side effects of chemotherapy. Case 3. Acute interstitial pneumonitis related to gemcitabine. J Clin Oncol 2000;18:697-698.
93. Pavlakis N, Bell DR, Millward MJ et al. Fatal pulmonary toxicity resulting from treatment with gemcitabine. Cancer 1997;80:286-291.
94. Burstein HJ. Side effects of chemotherapy. Case 1. Radiation recall dermatitis from gemcitabine. J Clin Oncol 2000;18:693-694.
95. Castellano D, Hitt R, Cortes-Funes H et al. Side effects of chemotherapy. Case 2. Radiation recall reaction induced by gemcitabine. J Clin Oncol 2000;18:695-696.
96. Hoffman JP, McGinn CJ, Ross E et al. A phase I trial of preoperative gemcitabine and radiotherapy followed by postoperative gemcitabine for patients with localized, resectable, pancreatic adenocarcinoma. Cancer Invest 1999;17:30-32.
97. Wolff R, Janjan N, Lenzi R et al. Treatment related toxicities with rapid-fractionation external beam radiation and concomitant gemcitabine for locally advanced nonmetastatic adenocarcinoma of the pancreas. Int J Radiat Oncol Biol Phys 1998;42:201.
98. Abad A, Arellano A, Brunet J et al. Gemcitabine plus radiotherapy in stage II-III pancreatic cancer: a phase I trial. Ann Oncol 1998;9:53.
99. Crane CH, Wolff RA, Abbruzzese JL et al. Combining gemcitabine with radiation in pancreatic cancer: understanding important variables influencing the therapeutic index. Semin Oncol 2001;28:25-33.
100. Zarba JJ, Jaremtchuk AV, Gonzalez Jazey P et al. A phase I-II study of weekly cisplatin and gemcitabine with concurrent radiotherapy in locally advanced cervical carcinoma. Ann Oncol 2003;14:1285-1290.
101. Wilkowski R, Thoma M, Duhmke E et al. Concurrent chemoradiotherapy with gemcitabine and cisplatin after incomplete (R1) resection of locally advanced pancreatic carcinoma. Int J Radiat Oncol Biol Phys 2004;58:768-772.
102. Brunner TB, Grabenbauer GG, Klein P et al. Phase I trial of strictly time-scheduled gemcitabine and cisplatin with concurrent radiotherapy in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 2003;55:144-153.
103. Symon Z, Davis M, McGinn CJ et al. Concurrent chemoradiotherapy with gemcitabine and cisplatin for pancreatic cancer: From the laboratory to the clinic. Int J Radiat Oncol Biol Phys 2002;53:140-145.
104. Benasso A, Corvo R, Ponzanelli A et al. Alternating gemcitabine and cisplatin with gemcitabine and radiation in stage IV squamous cell carcinoma of the head and neck. Ann Oncol 2004;15:646-652.
105. Muler JH, McGinn CJ, Normolle D et al. Phase I trial using a time-to-event continual reassessment strategy for dose escalation of cisplatin combined with gemcitabine and radiation therapy in pancreatic cancer. J Clin Oncol 2004;22:238-243.
106. Caffo O, Fellin G, Graffer U et al. Phase I study of gemcitabine and radiotherapy plus cisplatin after transurethral resection as conservative treatment for infiltrating bladder cancer. Int J Radiat Oncol Biol Phys 2003;57:1310-1316.
107. Martenson JA, Vigliotti AP, Pitot HC et al. A phase I study of radiation therapy and twice-weekly gemcitabine and cisplatin in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 2003;55:1305-1310.
108. Vokes E E, Herndon JE 2nd, Crawford J et al. Randomized phase II study of cisplatin with gemcitabine or paclitaxel or vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy for stage IIIB non-small-cell lung cancer: cancer and leukemia group B study 9431. J Clin Oncol 2002;20:4191-4198.
109. Safran H, Dipetrillo T, Iannitti D et al. Gemcitabine, paclitaxel, and radiation for locally advanced pancreatic cancer: a phase I trial. Int J Radiat Oncol Biol Phys 2002;54:137-141.
110. Kornek GV, Potter R, Selzer E et al. Combined radiochemotherapy of locally advanced unresectable pancreatic adenocarcinoma with mitomycin C plus 24-hour continuous infusional gemcitabine. Int J Radiat Oncol Biol Phys 2001;49:665-671.
111. Duenas Gonzales A, Vasquez Govea E, Lopez Graniel CM et al. Phase II randomized study of cisplatin vs cisplatin/gemcitabine concurrent to radiation in cervical cancer stages IB2-IIB. Proc Am Soc Clin Oncol 2003;22:1858a.
112. Kachnic LA, Shaw JE, Manning M A et al. Gemcitabine following radiotherapy with concurrent 5-fluorouracil for nonmetastatic adenocarcinoma of the pancreas. Int J Cancer 2001;96:132-139.
113. Al-Sarraf M, LeBlanc M, Giri PG et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol 1998;16:1310-1317.
114. Hughes TL, Hahn TM, Reynolds KK et al. Kinetic analysis of human deoxycytidine kinase with the true phosphate donor uridine triphosphate. Biochemistry 1997;36:7540-7547.
115. Abbruzzese JL, Grunewald R, Weeks EA et al. A phase I clinical, plasma, and cellular pharmacology study of gemcitabine. J Clin Oncol 1991;9:491-498.
116. Grunewald R, Kantarjian H, Keating MJ et al. Pharmacologically directed design of the dose rate and schedule of 2′,2′-difluorodeoxycytidine (gemcitabine) administration in leukemia. Cancer Res 1990;50:6823-6826.
117. Tempero M, Plunkett W, van Haperen VR et al. Randomized phase II comparison of dose-intense gemcitabine: thirty-minute infusion and fixed dose rate infusion in patients with pancreatic adenocarcinoma. J Clin Oncol 2003;21:3402-3408.
118. Rockwell S, Grindey GB. Effect of 2′,2′-difluorodeoxycytidine on the viability and radiosensitivity of EMT6 cells in vitro. Oncol Res 1992;4:151-155.
119. Crane CH, Janjan NA, Evans DB et al. Toxicity and efficacy of concurrent gemcitabine and radiotherapy for locally advanced pancreatic cancer. Int J Gastrointest Cancer 2001;29:9-18.
120. Weller M, Streffer J, Wick W et al. Preirradiation gemcitabine chemotherapy for newly diagnosed glioblastomas. A phase II study. Cancer 2001;91:423-427.
121. Trodella L, Granone P, Valente S et al. Phase I trial of weekly gemcitabine and concurrent radiotherapy in patients with inoperable non-small-cell lung cancer. J Clin Oncol 2002;20:804-810.
122. Poggi MM, Kroog GS, Russo A et al. Phase I study of weekly gemcitabine as a radiation sensitizer for unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys 2002;54:670-676.