Abstract
Continuous infusion of chemotherapy is one of the developments to try to improve the treatment of metastic cancer. There is a sound theoretical rationale to deliver cytotoxic drugs as a continuous infusion. Furthermore, the development of reliable venous access devices and portable infusion pumps enables patients to be treated in an ambulatory setting. This review focuses on the continuous infusion of the most frequently used drugs: 5‐fluorouracil (5‐FU) and fluorodeoxyuridine (FUDR). An overview is given of both preclinical studies and studies in humans. Continuous infusion of 5‐FU and FUDR has proven to be feasible in all studies. However, the results (response rate and especially survival) are rather disappointing. So far, continuous infusion of cytostatic drugs can stil be considered as an experimental procedure. Whether protracted, intermittent or circadian modulated continuous infusion is the optimal treatment schedule has still to be proven in future studies. Furthermore, studies are needed to demonstrate whether dose intensity for most tumours is important for treatment outcome. Also, studies are needed to investigate quality of life and economic issues.
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References
Steel GG. Growth kinetics of tumours. Oxford: Clarendon Press, 1977.
Wilson GD. Assessment of human tumour proliferation using bromodeoxyuridine-current status. Acta Oncol 1991;30: 903–10.
Rew DA, Campbell ID, Taylor I, Wilson GD. Proliferation indices of invasive breast carcinomas after in vivo 5-bromo-2'-deoxyuridine labelling: a flow cytometric study of 75 tumours. Br J Surg 1992;79: 335–9.
Riccardi A, Danova M, Wilson G, Ucci G, Dörmer P, Mazzini G, Brugnatelli S, Girino M, McNally NJ, Ascari E. Cell kinetics in human malignancies studied with in vivo administration of bromodeoxyuridine and flow cytometry. Cancer Res 1988;48: 6238–45.
Rew DA, Thomas DJ, Coptcoat M, Wilson GD. Measurement of in vivo urological tumour cell kinetics using multiparameter flow cytometry. Preliminary study. Br J Urol 1991;68: 44–8.
McNally NJ. Can cell kinetic parameters predict the response of tumours to radiotherapy? Int J Radiat Biol 1989;56: 777–86.
Watson JV. Tumour growth dynamics. Br Med Bull 1991;47: 47–63.
Matsushima Y, Kanzawa F, Hoshi A, Shimizu E, Nomori H, Sasaki Y, Saijo N. Time-schedule dependency of the inhibiting activity of various anticancer drugs in the clonogenic assay. Cancer Chemother Pharmacol 1985;14: 104–7.
Hryniuk WM, Figueredo A, Goodyear M. Application of dose intensity to problems in chemotherapy of breast and colorectal cancer. Sem Oncol 1978;14(Suppl 4): 3–11.
Anderson N, Lokich J. Controversial issues in 5-fluorouracil infusion use. Cancer 1992;70: 998–1002.
Bothe A, Piccione W, Ambrosino JJ, Benotti PN, Lokich JJ. Implantable central venous access system. Am J Surg 1984;147: 565–9.
Wenzel DA, Forsythe P. Quality of life assessment of protracted continuous ambulatory infusion of 5-fluorouracil. J Inf Chemother 1993;3: 22–4.
Poorter RL, Lauw FN, Bemelman WA, Bakker PJM, Taat CW, Veenhof CHN. Complications of an implantable venous access device (Port-a-Cath®) during intermittent continuous infusion of chemotherapy. Eur J Cancer 1996;32A: 2262–6.
Vogelzang NJ. Continuous infusion chemotherapy: a critical review. J Clin Oncol 1994;2: 1289–1304.
Pinedo HM, Peters GJ. Fluorouracil: biochemistry and pharmacology. J Clin Oncol 1988;6: 1653–64.
Diasio RB, Harris BE. Clinical pharmacology of 5-fluorouracil. Clin Pharmacokinet 1989;16: 215–37.
Drewinko B, Yang LY. Cellular basis for the inefficacy of 5-FU in human colon carcinoma. Cancer Treat Rep 1985;12: 1391–8.
Calabro-Jones PM, Byfield JE, Ward JF, Sharp TR. Time-dose relationships for 5-fluorouracil cytotoxicity against human epithelial cancer cells in vitro. Cancer Res 1982;42: 4413–20.
Laskin JD, Evans RM, Slocum HK, Burke D, Hakala MT. Basis for natural variation in sensitivity to 5-fluorouracil in mouse and human cells in culture. Cancer Res 1979;39: 282–90.
Drewinko B, Yang LY, Ho DHW, Benvenuto J, Loo TL, Freireich EJ. Treatment of cultured human colon carcinoma cells with fluorinated pyrimidines. Cancer 1980;45: 1144–58.
Santelli G, Valeriote F. Schedule-dependent cytotoxicity of 5-fluorouracil in mice. J Natl Cancer Inst 1986;76: 159–64.
Sakaguchi Y, Stephens LC, Makino M, Kaneko T, Strebel FR, Danhauser LL, Jenkins GN, Bull JMC. Apoptosis in normal tissues induced by 5-fluorouracil: comparison between bolus injection and prolonged infusion. Anticancer Res 1994;14: 1489–92.
Reinberg A, Smolensky M, Levi F. Clinical chronopharmacology. Biomedicine 1981;34: 171–8.
Hrushesky WJM. Chemotherapy: Circadian timing and toxicity. In: Perry MC, ed. Chemotherapy source book. Baltimore: Williams and Wilkins, 1992: 165–212.
Peters GJ, van Dijk J, Nadal JC, Van Groeningen CJ, Lankelma J, Pinedo HM. Diurnal variation in the therapeutic efficacy of 5-fluorouracil against murine colon cancer. In Vivo 1987;1: 113–18.
Burns ER, Beland SS. Effect of biological time on the determination of the LD50 of 5-fluorouracil in mice. Pharmacol 1984;28: 296–300.
Popovic P, Popovic V, Baughman J. Circadian rhythm and 5-fluorouracil toxicity in C3H mice. Biomed Therm 1982;25: 185–7.
Gonzales JL, Sothern RB, Thatcher G, Nguyen N, Hrushesky WJM. Substantial difference in timing of murine circadian susceptibility to 5-fluorouracil and FUDR. Proc Am Assos Cancer Res 1989;30: 616 (abstract).
Minshull M, Gardner MLG. The effect of time of administration of 5-fluorouracil on leucopenia in the rat. Eur J Cancer Clin Oncol 1984;20: 857–8.
Gardner MLG, Plumb JA. Diurnal variation in the intestinal toxicity of 5-fluorouracil in the rat. Clin Sci 1981;61: 717–22.
Sullivan RD, Young CW, Miller E, Glatstein N, Clarkson B, Burchenal JH. The clinical effects of the continuous administration of fluorinated pyrimidines (5-fluorouracil and 5-fluoro-2'-deoxyuridine). Cancer Chemother Rep 1960;8: 77–83.
Seifert P, Baker LH, Reed ML, Vatkevicius VK. Comparison of continuously infused 5-fluorouracil with bolus injection in treatment of patients with colorectal adenocarcinoma. Cancer 1975;36: 123–8.
Lokich JJ, Moore C. Chemotherapy-associated palmar-plantar erythrodysesthesia syndrome. Ann Intern Med 1984;101: 798–800.
Fraile RJ, Baker LH, Buroker TR, Horwitz J, Vaitkevicius VK. Pharmacokinetics of 5-fluorouracil administered orally, by rapid intravenous and by slow infusion. Cancer Res 1980;40: 2223–8.
Lokich J, Bothe A, Fine N, Perri J. Phase I study of protracted venous infusion of 5-fluorouracil. Cancer 1981;48: 2565–8.
Lynch TJ, Kalish LA, Kass F, Strauss G, Elias A, Skarin A, Shulman L, Sugarbaker D, Frei E. Continuous-infusion cisplatin, 5-fluorouracil, and leucovorin for advanced non-small cell lung cancer. Cancer 1994;73: 1171–6.
Pazdur R, Ajani JA, Patt YZ, Gomez J, Bready B, Levin B. Phase II evaluation of recombinant alpha-2a-interferon and continuous infusion fluorouracil in previously untreated metastatic colorectal adenocarcinoma. Cancer 1993;71: 1214–18.
Ragnhammar P, Blomgren H, Edler D, Lundell G, Magnusson I, Sonnenweld T. Different dose regimens of 5-fluorouracil and interferon-α ?in patients with metastatic colorectal carcinoma. Eur J Cancer 1995;31A: 315–20.
Goodman HM, Dottino PR, Kredenster D, Mark M, Runowicz C, Cohen CJ. Continuous infusion fluoropyrimidines as salvage therapy for patients with advanced ovarian carcinoma. Gynecol Oncol 1988;29: 348–55.
Bitran JD, Kozloff MF, Desser RK. Platinol (CDDP) and continuous intravenous infusion 5-fluorouracil in refractory stage IV breast cancer: a phase II study. Cancer Invest 1990;8: 335–8.
Lacava AJ, Baron FJ, Anton LM, Estrata E, De Sande LM, Palacio I, Esteban E, Gracia JM, Buesa JM, Fernandez OA, Gonzalez Baron M. Combination chemotherapy with cisplatin and 5-fluorouracil 5-day infusion in the therapy of advanced gastric cancer: a phase II trial. Ann Oncol 1991;2: 751–4.
Tsavaris N, Karagiaouris P, Vonorta K, Bacogianis H, Milonakis N, Karvounis N, Kakoliris S, Zepou E, Karabelis A, Papazahariou M, Robotas M, Kosmidis P. Concomitant administration of 4-hydroxypyrazolopyrimidine (allopurinol) and high-dose continuous infusion 5-fluorouracil. Oncology 1990;47: 70–4.
Ardalan B, Jamin D, Jayaram HN, Presant CA. Phase I study of continuous-infusion PALA and 5-FU. Cancer Treat Rep 1984;68: 531–4.
Kemeny N, Israel K, Niedzwiecki D, Chapman D, Botet J, Minsky B, Vinciguerra V, Rosenbluth R, Bosselli B, Cochran C, Sheehan K. Randomized study of continuous infusion fluorouracil versus fluorouracil plus cisplatin in patients with metastatic colorectal cancer. J Clin Oncol 1990;8: 313–18.
Diaz-Rubio E, Jimeno J, Anton A, Aranda E, Sanchez J, Massuti B, Cruz-Hernandez J, Carrato A, Martin M, Belon J, Gonzalez R, Milla A, Sanchiz F, Balana C, Lizon J, Diaz-Faes J, Alonso A, Navarette A, Sanz Ortiz J, Camps C, del Moral F. A prospective randomized trial of continuous infusion 5-fluorouracil (5-FU) versus 5-FU plus cisplatin in patients with advanced colorectal cancer. A trial of the Spanish Cooperative Group for Digestive Tract Tumor Therapy (T.T.D.). Am J Clin Oncol 1992;15: 56–60.
Lokich J, Fine N, Peri J, Bothe A. Protracted ambulatory venous infusion of 5-fluorouracil. Am J Clin Oncol 1983;6: 103–7.
Huan S, Pazdur R, Singhakowinta A, Samal B, Vaitkevicius VK. Low-dose continuous infusion 5-fluorouracil. Evaluation in advanced breast carcinoma. Cancer 1989;63: 419–22.
Lokich J, Schulz J, Rosenthal CJ, Fryer J, Fryer D. Infusional single agent 5-fluorouracil for advanced breast cancer: thirdline therapy candidate for moving to first line. J Infus Chemother 1993;3: 77–9.
Hansen R, Quebbeman E, Ausman R, Frick J, Ritch P, Schulte W, Haas C, Beatty P, Anderson T. Continuous systemic 5-fluorouracil infusion in advanced colorectal cancer: results in 91 patients. J Surg Oncol 1989; 40: 177–81.
Rougier P, Ammarguellat H, Ghosn M, Piot G, Benhamed M, Tigaud JM, Laplaige P, Theodore C, Kac J, Goldberg J, Carde P, Droz JP. Phase II trial of 7-day continuous 5-fluorouracil infusion in the treatment of advanced colorectal carcinoma. Oncology 1992;49: 35–9.
Poorter RL, Bakker PJM, Taat CW, Veenhof CHN. Intermittent continuous infusion of 5-fluorouracil; a useful approach in disseminated colorectal cancer? Eur J Cancer 1993;29A:775.
Findlay M, Hill A, Cunningham D, Normal A, Nicolson M, Ford H, Husband J, Evans C, Carter R. Protracted venous infusion 5-fluorouracil and interferon-α? in advanced and refractory colorectal cancer. Ann Oncol 1994;5: 239–43.
Lokich JJ, Ahlgren JD, Gullo JJ, Philips JA, Fryer JG. A prospective randomized comparison of continuous infusion fluorouracil with a conventional bolus schedule in metastatic colorectal carcinoma: a Mid-Atlantic Oncology Program Study. J Clin Oncol 1989;7: 425–32.
Weinerman B, Shah A, Fields A, Cripps IC, Wilson K, McCormick R, Temple W, Maroun J, Bogues W, Pater J, Zee B. Systemic infusion versus bolus chemotherapy with 5-fluorouracil in measurable metastatic colorectal cancer. Am J Clin Oncol 1992;15: 518–23.
Caudry M, Bonnel C, Floquet A, Marsault C, Quetin P, Pujol J, Matson O, Dujols J-P, Caudry Y, Skawinski P, Carenco J, Makhtari F, Celerier D, Quinton A, Demeaux H, Maire J-P. A randomized study of bolus fluorouracil plus folinic acid versus 21-day fluorouracil infusion alone or in association with cyclophosphamide and mitomycin C in advanced colorectal carcinoma. Am J Clin Oncol 1995;18: 118–25.
Harris BE, Song R, Soong S, Diasio RB. 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 1990;50: 197–201.
Tuchman M, von Roemeling R, Lanning R, et al. Source of variability of dihydropyrimidine dehydrogenase (DPD) activity in human blood mononuclear cells. In: Reinberg A, Smolensky M, Labrecque G, eds. Annual review of chronopharmacology. Vol 5. New York: Pergamon Press, 1988: 399–402.
Petit E, Milano G, Levi F, Thyss A, Bailleul F, Schneider M. Circadian rhythm-varying plasma concentration of 5-fluorouracil during a five-day continuous venous infusion at a constant rate in cancer patients. Cancer Res 1988;48: 1676–9.
Levi F, Soussan A, Adam R, Caussanel JP, Metzger G, Misset JL, Descorps-Declères, Kustlinger F, Lorphelin D, Jasmin C, Bismuth H, Reinberg A, Mathé G. Programmable-in-time pumps for chronotherapy of patients (pts) with colorectal cancer with 5-day circadian-modulated venous infusion of 5-fluorouracil (CVI-5FUra). Proc Am Soc Clin Oncol 1989;8: 111 (abstract).
Levi F, Misset J-L, Brienza S, Adam R, Metzger G, Itzhaki M, Caussanel J-P, Kunstlinger F, Lecouturier S, Descorps-Declere A, Jasmin C, Bismuth H, Reinberg A. A chronopharmacologic phase II clinical trial with 5-fluorouracil, folinic acid, and oxiliplatin using an ambulatory multichannel programmable pump. High antitumor effectiveness against metastatic colorectal cancer. Cancer 1992;69: 893–900.
Levi FA, Zidani R, Vannetzel J-M, Perpoint B, Focan C, Faggiuolo R, Chollet P, Garufi C, Itzhaki M, Dogliotti L, Iacobelli S, Adam R, Kunstlinger F, Gastiaburu J, Bismuth H, Jasmin C, Misset J-L. Chronomodulated versus fixed-infusion-rate delivery of ambulatory chemotherapy with oxaliplatin, fluorouracil, and folinic acid (leucovorin) in patients with colorectal cancer metastases: a randomized multi-institutional trial. J Natl Cancer Inst 1994;86: 1608–17.
Bjarnason GA, Kerr IG, Doyle N, Macdonald M, Sone M. Phase I study of 5-fluorouracil and leucovorin by a 14-day circadian infusion in metastatic adenocarcinoma patients. Cancer Chemother Pharmacol 1993;33: 221–8.
Anderson N, Lokich J, Bern M, Wallach S, Moore C, Williams D. A phase I clinical trial of combined fluoropyrimidines with leucovorin in a 14-day infusion. Demonstration of biochemical modulation. Cancer 1989;63: 233–7.
Leichman CG, Leichman L, Spears CP, Rosen PJ, Jeffers S, Groshen S. Prolonged continuous infusion of fluorouracil with weekly bolus leucovorin: a phase II study in patients with disseminated colorectal cancer. J Natl Cancer Inst 1993;85: 41–4.
Grem JL, McAtee N, Balis F, Murphy R, Venzon D, Kramer B, Goldspiel B, Begley M, Allegra CJ. A phase II study of continuous infusion 5-fluorouracil and leucovorin with weekly cisplatin in metastatic colorectal carcinoma. Cancer 1993;72: 663–8.
Poorter RL, Peters GJ, Bakker PJM, Taat CW, Biermans-van Leeuwe DMJ, Codacci-Pisanelli G, Noordhuis P, Oosting J, Veenhof CHN. Intermittent continuous infusion of 5-fluorouracil and low dose oral leucovorin in patients with gastrointestinal cancer: relationship between plasma concentrations and clinical parameters. Eur J Cancer 1995;31A: 1465–70.
Ahlgren JD, Trocki O, Gullo JJ, Goldberg R, Muir WA, Sisk R, Schacter L. Protracted infusion of 5-FU with weekly low-dose cisplatin as second-line therapy in patients with metastatic colorectal cancer who have failed 5-FU monotherapy. Cancer Inv 1992;9: 27–33.
Lokich JJ, Ahlgren JD, Cantrell J, Heim WJ, Wampler GL, Gullo JJ, Fryer JG, Alt DE. A prospective randomized comparison of protracted infusional 5-fluorouracil with or without weekly bolus cisplatin in metastatic colorectal carcinoma. A Mid-Atlantic Oncology Program Study. Cancer 1991;67: 14–19.
Iveson TJ, Ramage FR, Walsh G, Jones AL, Smith IE. Preliminary report on continuous infusional 5-fluorouracil with epirubicin and cisplatin in the treatment of locally advanced metastatic breast cancer. J Infus Chemother 1993;3: 19–21.
Jones AL, Smith IE, O'Brien ME, Talbot D, Walsh G, Ramage F, Robertshaw H, Ashley S. Phase II study of continuous infusion fluorouracil with epirubicin and cisplatin in patients with metastatic and locally advanced breast cancer: an active new regimen. J Clin Oncol 1994;12: 1259–65.
Findlay M, Cunningham D, Norman A, Mansi J, Nicolson M, Hickish T, Nicolson V, Nash A, Sacks N, Ford H, Carter R, Hill A. A phase II study in advanced gastro-esophageal cancer using epirubicin and cisplatin in combination with continuous infusion 5-fluorouracil (ECF). Ann Oncol 1994;5: 609–16.
Highley MS, Parnis FX, Trotter GA, Houston SJ, Penson RT, Harper PG, Mason RC. Combination chemotherapy with epirubicin, cisplatin and 5-fluorouracil for the palliation of advanced gastric and oesophageal adenocarcinoma. Br J Surg 1994;81: 1763–5.
Poorter RL, Bakker PJM, Fockens P, Taat CW, Bartelsman JFW, Veenhof CHN. Intermittent continuous infusion of 5-fluorouracil in combination with epirubicin and cisplatin in advanced gastric cancer: the importance of dose intensity. J Infus Chemother 1996;6: 87–91.
Villar-Grimalt A, Candel MT, Delgado F, Garcia-Reinoso J, Sanchis C, Viciano V, Asencio F, Martinez-Abad M, Aguilo J, Sanchez JJ. 120-hour 5-fluorouracil (5-FU) continuous infusion infusion (CI) plus BCNU in advanced colorectal cancer. Am J Clin Oncol 1991;14: 387–92.
Lokich JJ, Phillips D, Green R, Paul S, Sonneborn H, Zipoli TE, Curt G. 5-Fluorouracil and methotrexate administered simultaneously as a continuous infusion. A phase I study. Cancer 1985;56: 2395–8.
Lokich J, Bern M, Anderson N, Wallach S, Moore C, Beauchamp K, Williams D. Cyclophosphamide, methotrexate, and 5-fluorouracil in a three-drug admixture. Phase I trial of 14-day continuous ambulatory infusion. Cancer 1989;63: 822–4.
Anderson N, Lokich J, Bern M, Wallach S, Moore C, Williams D, Umprayn V. Combined 5-fluorouracil and floxuridine administered as a 14-day infusion. A phase I study. Cancer 1989;63: 825–7.
Poorter RL, Bakker PJM, Huizing MT, Taat CW, Rietbroek RC, Gouma DJ, Rauws EAJ, Veenhof CHN. Intermittent continuous infusion of ifosfamide and 5-fluorouracil in patients with advanced adenocarcinoma of the pancreas. Ann Oncol 1995;6: 1048–9.
Shah A, MacDonald W, Goldie J, Gudauskas G, Brisebois B. 5-FU infusion in advanced colorectal cancer: a comparison between three dose schedules. Cancer Treat Rep 1985;69: 739–42.
Chabner BA, Collins JM. Cancer chemotherapy: principles and practice. Philadelphia: J.B. Lippincott Company, 1990.
Von Roemeling R, Mormont MC, Walker K, Olshefski R, Langevin T, Rabatin J, Wick M, Hrushesky W. Cancer control depends upon the circadian shape of continuous FUDR infusion. Proc Am Assoc Cancer Res 1987;28: 326.
Von Roemeling R, Hrushesky WJM. Determination of the therapeutic index of floxuridine by its circadian infusion pattern. J Natl Cancer Inst 1990;82: 386–93.
Sullivan RD, Miller E. The clinical effects of prolonged intravenous infusion of 5-fluoro-2'-deoxyuridine. Cancer Res 1965;25: 1025–30.
Lokich JJ, Sonneborn H, Paul S, Zipoli T. Phase I study of continuous venous infusion of floxuridine (5-FUDR) chemotherapy. Cancer Treat Rep 1983;67: 791–3.
moertel CG, Reitemeier RJ, Hahn RG. Controlled comparison of 5-fluoro-2'-deoxyuridine therapy administered by rapid intravenous injection and by continuous intravenous infusion. Cancer Res 1967;27: 549–52.
Lokich J, Anderson N, Bern M, Wallach S, Moore C, Williams D, Umprain V. Combined floxuridine® and cisplatin in a fourteen day infusion. Phase I study. Cancer 1988;62: 2309–12.
Lokich J, Moore C, Anderson N, Bern M. Infusion of floxuridine plus etoposide plus cisplatin in human malignancies. Eur J Cancer 1991;27;1593–6.
Wilkinson MJ, Frye JW, Small EJ, Venook AP, Carroll PR, Ernest ML, Stagg RJ. A phase II study of constant-infusion floxuridine for the treatment of metastatic renal cell carcinoma. Cancer 1993;71: 3601–4.
Stadler WM, Vogelzang NJ, Vokes EE, Charette J, Whitman G. Continuous-infusion fluorodeoxyuridine with leucovorin and high-dose interferon: a phase II study in metastatic renal-cell cancer. Cancer Chemother Pharmacol 1992;31: 213–16.
Falcone A, Cianci C, Ricci S, Brunetti I, Bertucelli M, Conte PF. Alpha-2b-interferon plus floxuridine in metastatic renal cell carcinoma. Cancer 1993;72: 564–8.
Small EJ, Frye JW, Wilkinson MJ, Carroll PR, Ernest ML, Stagg RJ. A phase I/II study of alternating constant rate infusion floxuridine with constant rate infusion vinblastine for the treatment of metastatic renal cell carcinoma. Cancer 1994;73: 2803–7.
Von Roemeling R, Hrushesky WJM. Circadian patterning of continuous floxuridine infusion reduces toxicity and allows higher dose intensity in patients with widespread cancer. J Clin Oncol 1989;7: 1710–19.
Hrushesky WJM, von Roemeling R, Lanning RM, Rabatin JT. Circadian-shaped infusions of floxuridine for progressive metastatic renal cell carcinoma. J Clin Oncol 1990;8: 1504–13.
Damascelli B, Marchianò A, Spreafico C, Lutman R, Salvetti M, Bonalumi MG, Mauri M, Garbagnati F, Del Nero A, Comeri G, Conti G, Coppoli S, Benetti G, Tralongo P, Belussi D. Circadian continuous chemotherapy of renal cell carcinoma with an implantable, programmable infusion pump. Cancer 1990;66: 237–41.
Dexeus FH, Logothetis CJ, Sella A, Amato R, Kilbourn R, Ogden S, Striegel A, Kwan J, Newman RA. Circadian infusion of floxuridine in patients with metastatic renal cell carcinoma. J Urol 1991;146: 709–13.
Natoli C, Irtelli L, Martino MT, Gallo-Stampino C, Criscuolo D, Santobuono F, Iacobelli S. A phase II evaluation of 5-fluoro-2-deoxyuridine (FUDR) administered as a 14-day continuous venous infusion at circadian-rhythm modulated rated in gastrointestinal cancer and renal cell carcinoma. J Infus Chemother 1994;4: 97–9.
Sampaio C, Olencki T, Murthy S, Budd GT, McLain D, Lorenzi V, Tuason L, Bukowski RM. Phase II trial of circadian infusion of the antimetabolite floxuridine in patients with metastatic renal cell carcinoma. J Infus Chemother 1994;4: 100–3.
Conroy T, Geoffrois L, Guillemin F, Luporsi E, Krakowski I, Spaëth D, Frasie V, Volff D. Simplified chronomodulated continuous infusion of floxuridine in patients with metastatic renal cell carcinoma. Cancer 1993;72: 2190–7.
Bjarnason GA, Hrushesky WJM, Diasio R, Harris J, Marsh R, Huben R, Lokich JJ, Anderson J. The international chronotherapy study group. Flat versus circadian modified 14 day infusion of FUDR for advanced renal cell cancer (RCC): a phase-III study. Proc Am Soc Clin Oncol 1994;13: 233 (abstract).
Lokich JJ, Moore CL, Anderson NR. Comparison of costs for infusion versus bolus chemotherapy administration: analysis of five standard chemotherapy regimens in three common tumors. Part one. Model projections for cost based on charges. Cancer 1996;78: 294–9.
Lokich JJ, Moore CL, Anderson NR. Comparison of costs for infusion versus bolus chemotherapy administration. Part two. Use of charges versus reimbursement for cost basis. Cancer 1996;78: 300–3.
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Poorter, R., Bakker, P. & Veenhof, C. Continuous infusion of chemotherapy: focus on 5‐fluorouracil and fluorodeoxyuridine.. Pharm World Sci 20, 45–59 (1998). https://doi.org/10.1023/A:1008605600414
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DOI: https://doi.org/10.1023/A:1008605600414