Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Drugs & Aging
Published in: Drugs & Aging 3/2000

01-09-2000 | Review Article

Progress in Colorectal Cancer Chemotherapy

How Far Have We Come, How Far to Go?

Authors: Melanie E. Royce, Dr Paulo M. Hoff, Richard Pazdur

Published in: Drugs & Aging | Issue 3/2000

Login to get access

Abstract

Fluorouracil has been the mainstay of treatment for colorectal cancer (CRC) for almost 40 years. Various schedules and biochemical modulators have been investigated in an attempt to improve the therapeutic efficacy of fluorouracil. To date, fluorouracil plus folinic acid represents the standard therapy in CRC for the adjuvant treatment of patients at high risk for relapse and for the first-line treatment of metastatic disease.
Combination chemotherapy regimens have not been developed due to the lack of other active agents. However, the availability of several novel agents now allows investigation of combination regimens in this disease. One group of such agents, the oral fluoropyrimidines (tegafur/uracil plus oral folinic acid, capecitabine, eniluracil plus oral fluorouracil, and tegafur/gimeracil/potassium oxonate), are convenient oral alternatives to intravenous fluorouracil. A particular advantage of these oral agents is the reduction in the incidence of febrile neutropenia and mucositis compared with fluorouracil given in an intravenous bolus schedule. To gain clinical acceptance, however, oral fluoropyrimidines must confer at least the same survival advantages associated with the optimal intravenous fluorouracil regimens.
Irinotecan and oxaliplatin are 2 other novel agents that have mechanisms of action that are uniquely different from those of fluorouracil, with demonstrated activity in patients with fluorouracil-refractory disease. Recent randomised trials comparing fluorouracil plus folinic acid with combinations of either irinotecan or oxaliplatin and fluorouracil plus folinic acid have shown that response rates are improved and time to progression is increased in patients receiving the combination regimens. These regimens are being rapidly introduced in the adjuvant setting, and the role and acceptance of these combination regimens as first-line therapy needs to be defined.
Other novel agents being evaluated in the treatment of patients with advanced CRC include oral edrecolomab (monoclonal antibody 17-1A) and tumour vaccines.
Future research is focused on enabling clinicians to individualise treatment strategies in patients with CRC, so as to improve clinical outcomes and reduce drug toxicity.
Literature
1.
Heidelberger C, Chandler NK, Douglas Jr H. Fluorouracil pyrimidine: a new class of tumor inhibiting compounds. Nature 1957; 179: 633–66CrossRef
2.
Ansfield F, Klotz J, Nealon T, et al. A phase II study comparing the clinical utility of four regimens of 5-fluorouracil: a preliminary report. Cancer 1977; 39: 34–40PubMedCrossRef
3.
Lokich JJ, Ahlgren JD, Guilo JJ, et al. 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(4): 425–32PubMed
4.
Meta-Analysis Group in Cancer. Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. J Clin Oncol 1998; 16(1): 301–8
5.
Hansen RM, Quebbeman E, Anderson T. 5-fluorouracil by protracted venous infusion: a review of current progress. Oncology 1989; 46(4): 245–50PubMedCrossRef
6.
Meta-Analysis Group In Cancer. Toxicity of fluorouracil in patients with advanced colorectal cancer: effect of administration schedule and prognostic factors. J Clin Oncol 1998; 16(11): 3537–41
7.
Pazdur R, Douillard JY, Skillings JR, et al. Multicenter phase III study of 5-fluorouracil (5-FU) or UFT in combination with leucovorin (LV) in patients with metastatic colorectal cancer [abstract no. 1009]. Proc Am Soc Clin Oncol 1999; 18: 263a
8.
Carmichael J, Popiela T, Radstone D, et al. Randomized comparative study of ORZEL [Oral Uracil/Tegafur (UFT) plus leucovorin (LV)] versus parenteral 5-fluorouracil (5-FU) plus LV in patients with metastatic colorectal cancer [abstract no. 1015]. Proc Am Soc Clin Oncol 1999; 18: 264a
9.
Twelves C, Harper P, Van Cutsem E, et al. A phase III trial (SO 14796) of Xeloda (capecitabine) in previously untreated advanced/metastatic colorectal cancer [abstract no. 1010]. Proc Am Soc Clin Oncol 1999; 18: 263a
10.
Cox JV, Pazdur R, Thibault A, et al. A phase III trial of XELODA (Capecitabine) in previously untreated advanced/metastatic colorectal cancer [abstract no. 1016]. Proc Am Soc Clin Oncol 1999; 18: 265a
11.
Saltz LB, Locker PK, Pirotta N, et al. Weekly irinotecan (CPT-11), leucovorin (LV), and fluorouracil (FU) is superior to daily x 5 LV/FU in patients (pts) with previously untreated metastatic colorectal cancer (CRC) [abstract no. 898]. Proc Am Soc Clin Oncol 1999; 18: 233a
12.
Douillard JY, Cunningham D, Roth AD, et al. A randomized phase III trial comparing irinotecan (IRI) + 5FU/folinic acid (FA) to the same schedule of 5FU/FA in patients with metastatic colorectal cancer as front line chemotherapy [abstract no. 899]. Proc Am Soc Clin Oncol 1999; 18: 233a
13.
Levi F, Dogliotti L, Perpoint B, et al. A multicenter phase II trial of intensified chronotherapy with oxaliplatin (L-OHP), 5-fluorouracil (5-FU) and folinic acid (FA) in patients (pts) with previously untreated metastatic colorectal cancer (MCC) [abstract no. 945]. Proc Am Soc Clin Oncol 1997; 18: 266a
14.
Giacchetti S, Zidani R, Perpoint B, et al. Phase III trial of 5-fluorouracil (5-FU), folinic acid (FA), with or without oxaliplatin (OXA) in previously untreated patients (pts) with metastatic colorectal cancer (MCC) [abstract no. 805]. Proc Am Soc Clin Oncol 1997; 16: 229a
15.
De Gramont A, Figer A, Seymour M, et al. A randomized trial of leucovorin (LV) and 5-fluorouracil (5-FU) with or without oxaliplatin in advanced colorectal cancer (CRC) [abstract no. 985]. Proc Am Soc Clin Oncol 1998; 17: 257a
16.
Allegra CJ, Grem JL. Antimetabolites in cancer. In: DeVita VT, Hellman S, Rosenberg SA, editors. Principles and practice of oncology. Philadelphia (PA): Lippincott-Rosen, 1997: 432–52
17.
Advanced Colorectal Cancer Meta-Analysis Project. Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: evidence in terms of response rate. J Clin Oncol 1992; 10(6): 896–903
18.
Poon MA, O’Connell MJ, Wieand HS, et al. Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer. J Clin Oncol 1991; 9(11): 1967–72PubMed
19.
Petrelli N, Douglass Jr HO, Herrera L, et al. The modulation of fluorouracil with leucovorin in metastatic colorectal carcinoma: a prospective randomized phase III trial. Gastrointestinal Tumor Study Group. J Clin Oncol 1989; 7(10): 1419–26PubMed
20.
Buroker TR, O’Connell MJ, Wieand HS, et al. Randomized comparison of two schedules of fluorouracil and leucovorin in the treatment of advanced colorectal cancer. J Clin Oncol 1994; 12(1): 14–20PubMed
21.
Leichman CG, Fleming TR, Muggia FM, et al. Phase II study of fluorouracil and its modulation in advanced colorectal cancer: a Southwest Oncology Group Study. J Clin Oncol 1995; 13(6): 1303–11PubMed
22.
De Gramont A, Bosset JF, Milan C, et al. Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with bimonthly high-dose leucovorin and fluorouracil bolus plus continuous infusion for advanced colorectal cancer: a French intergroup study. J Clin Oncol 1997; 15(2): 808–15PubMed
23.
Wadler S, Schwartz EL, Goldman M, et al. Fluorouracil and recombinant alfa-2a-interferon: an active regimen against advanced colorectal carcinoma. J Clin Oncol 1989; 7(12): 1769–75PubMed
24.
Pazdur R, Ajani JA, Patt YZ, et al. Phase II study of fluorouracil and recombinant interferon alfa-2a in previously untreated advanced colorectal carcinoma. J Clin Oncol 1990; 8(12): 2027–31PubMed
25.
Kemeny N, Younes A, Seiter K, et al. Interferon alpha-2a and 5-fluorouracil for advanced colorectal carcinoma: assessment of activity and toxicity. Cancer 1990; 66(12): 2470–5PubMedCrossRef
26.
Hill M, Norman A, Cunningham D, et al. Royal Marsden phase III trial of fluorouracil with or without interferon alfa-2b in advanced colorectal cancer. J Clin Oncol 1995; 13(6): 1297–302PubMed
27.
Corfu-A Study Group. Phase III randomized study of two fluorouracil combinations with either interferon alfa-2a or leucovorin for advanced colorectal cancer. J Clin Oncol 1995; 13(4): 921–8
28.
Kohne CH, Wilke H, Hecker H, et al. Interferon-alpha does not improve the antineoplastic efficacy of high-dose infusional 5-fluorouracil plus folinic acid in advanced colorectal cancer: first results of a randomized multicenter study by the Association of Medical Oncology of the German Cancer Society (AIO). Ann Oncol 1995; 6(5): 461–6PubMed
29.
Kosmidis PA, Tsavaris N, Skarlos D, et al. Fluorouracil and leucovorin with or without interferon alfa-2b in advanced colorectal cancer: analysis of a prospective randomized phase III trial: Hellenic Cooperative Oncology Group. J Clin Oncol 1996; 14(10): 2682–7PubMed
30.
Seymour MT, Slevin ML, Kerr DJ, et al. Randomized trial assessing the addition of interferon alpha-2a to fluorouracil and leucovorin in advanced colorectal cancer. Colorectal Cancer Working Party of the United Kingdom Medical Research Council. J Clin Oncol 1996; 14(8): 2280–8PubMed
31.
Recchia F, Nuzzo A, Lalli A, et al. Randomized trial of 5-fluorouracil and high-dose folinic acid with or without alpha-2B interferon in advanced colorectal cancer. Am J Clin Oncol 1996; 19(3): 301–4PubMedCrossRef
32.
Wolmark N, Bryant J, Hams DM, et al. The relative efficacy of 5-FU + leucovorin (FU-LV) and 5-FU-LV + interferon alfa-2a (IFN) in patients with Dukes’ B and C carcinoma of the colon: first report of NSABP C-05 [abstract no. 985]. Proc Am Soc Clin Oncol 1998; 17: 255a
33.
Romanini A, Li WW, Colofiore JR, et al. Leucovorin enhances cytotoxicity of trimetrexate/fluorouracil but not methotrexate/fluorouracil in CCRF-CEM cells. J Natl Cancer Inst 1992; 84(13): 1033–8PubMedCrossRef
34.
Conti JA, Kemeny N, Seiter K, et al. Trial of sequential trimetrexate, fluorouracil, and high-dose leucovorin in previously treated patients with gastrointestinal carcinoma. J Clin Oncol 1994; 12(4): 695–700PubMed
35.
Diasio RB. The role of dihydropyrimidine dehydrogenase (DPD) modulation in 5-FU pharmacology. Oncology 1998; 12 (10 Suppl. 7): 23–7PubMed
36.
Hoff PM, Pazdur R, Benner SE, et al. UFT and leucovorin:a review of its clinical development and therapeutic potential in the oral treatment of cancer. Anticancer Drugs 1998; 9: 479–90PubMed
37.
Miwa M, Ura M, Nishida M, et al. Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. Eur J Cancer 1998; 34(8): 1274–81PubMedCrossRef
38.
Findlay M, Van Cutsem E, Kocha W, et al. A randomized phase II study of Xeloda (capecitabine) in patients with advanced colorectal cancer [abstract no. 798]. Proc Am Soc Clin Oncol 1997; 16: 227a
39.
Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993; 85(5): 365–76PubMedCrossRef
40.
Porter DJT, Chestnut WG, Merril BM. Mechanism-based inactivation of dihydropyrimidine dehydrogenase by 5-ethynyluracil. J Biol Chem 1992; 267: 5236–42PubMed
41.
Baker SD, Khor SP, Adjei AA, et al. Pharmacokinetic, oral bioavailability, and safety study of fluorouracil in patients treated with 776C85, an inactivator of dihydropyrimidine dehydrogenase. J Clin Oncol 1996; 14(12): 3085–96PubMed
42.
Schilsky RL, Hohneker J, Ratain MJ, et al. Phase I clinical and pharmacologic study of eniluracil plus fluorouracil in patients with advanced cancer. J Clin Oncol 1998; 16(4): 1450–7PubMed
43.
Mani S, Beck T, Chevlen E, et al. A phase II open-label study to evaluate a 28-day regimen of oral 5-fluorouracil (5-FU) plus 776C85 for the treatment of patients with previously untreated metastatic colorectal cancer (CRC) [abstract no. 1083]. Proc Am Soc Clin Oncol 1998; 17: 281a
44.
Shirasaka T, Shimamato Y, Ohshimo H, et al. Development of a novel form of an oral 5-fluorouracil derivative (S-1) directed to the potentiation of the tumor selective cytotoxicity of 5-fluorouracil by two biochemical modulators. Anticancer Drugs 1996; 7(5): 548–57PubMedCrossRef
45.
Takechi T, Nakano K, Uchida J, et al. Antitumor activity and low intestinal toxicity of S-l, a new formulation of oral tegafur, in experimental tumor models in rats. Cancer Chemother Pharmacol 1997; 39(3): 205–11PubMedCrossRef
46.
Fukushima M, Shimamoto Y, Kato T, et al. Anticancer activity and toxicity of S-1, an oral combination of tegafur and two biochemical modulators, compared with continuous i.v. infusion of 5-fluorouracil. Anticancer Drugs 1998; 9(9): 817–23PubMedCrossRef
47.
Baba H, Ohtsu A, Sakata Y, et al. Late phase II study of S-1 in patients with advanced colorectal cancer in Japan [abstract no. 1065]. Proc Am Soc Clin Oncol 1998; 17: 277a
48.
Kunimoto T, Nitta K, Tanaka T, et al. Antitumor activity of 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy-camptothecin, a novel water-soluble derivative of camptothecin, against murine tumors. Cancer Res 1987; 47(22): 5944–7PubMed
49.
Rougier P, Bugat R, Douillard JY, et al. Phase II study of irinotecan in the treatment of advanced colorectal cancer in chemotherapy-naive patients and patients pretreated with fluorouracil-based chemotherapy. J Clin Oncol 1997; 15(1): 251–60PubMed
50.
Conti JA, Kemeny NE, Saltz LB, et al. Irinotecan is an active agent in untreated patients with metastatic colorectal cancer. J Clin Oncol 1996; 14(3): 709–15PubMed
51.
Pitot HC, Wender DB, O’Connell MJ, et al. Phase II trial of irinotecan in patients with metastatic colorectal carcinoma. J Clin Oncol 1997; 15(8): 2910–9PubMed
52.
Rothenberg ML, Eckardt JR, Kuhn JG, et al. Phase II trial of irinotecan in patients with progressive or rapidly recurrent colorectal cancer. J Clin Oncol 1996; 14(4): 1128–35PubMed
53.
Pitot HC. US pivotal studies of irinotecan in colorectal carcinoma. Oncology (Hunting!) 1998; 12 (8 Suppl. 6): 48–53
54.
Cunningham D, Pyrhonen S, James RD, et al. Randomized trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. Lancet 1998; 352(9138): 1413–8PubMedCrossRef
55.
Rougier P, Van Cutsem E, Bajetta E, et al. Randomised trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer. Lancet 1998; 352(9138): 1407–12PubMedCrossRef
56.
Pazdur R. Irinotecan: toward clinical end points in drug development. Oncology (Hunting!) 1998; 12 (8 Suppl. 6): 13–21
57.
Streit M, Jaehde U, Stremetzne S, et al. Five-day continuous infusion of 5-fluorouracil and pulsed folinic acid in patients with metastatic colorectal carcinoma: an effective secondline regimen. Ann Oncol 1997; 8(11): 163–5PubMedCrossRef
58.
Durrani A, Benhammouda MA, Delgado G, et al. Combination of irinotecan with leucovorin and 5-FU in advanced colorectal carcinoma: a phase II study [abstract no. 1083]. Proc Am Soc Clin Oncol 1999; 18: 282a
59.
Sallz LB, Kanowilz J, Kemeny NE, et al. Phase I clinical and pharmacokinetic study of irinotecan, fluorouracil, and leucovorin in patients with advanced solid tumors. J Clin Oncol 1996; 14(11): 2959–67
60.
Butour JL, Mazard AM, Macquet JP. Kinetics of the reaction of cis-platinum compounds with DNA in vitro. Biochem Biophys Res Commun 1985; 133(1): 347–53PubMedCrossRef
61.
Raymond E, Chaney SG, Taamma A, et al. Oxaliplatin: a review of preclinical and clinical studies. Ann Oncol 1998; 9(10): 1053–71PubMedCrossRef
62.
Giacchetti S, Brienza S, Focan C, et al. Contribution of second line oxaliplatin-chronomodulated 5-fluorouracil-folinic acid and surgery to survival in metastatic colorectal cancer patients [abstract no. 1050]. Proc Am Soc Clin Oncol 1998; 17: 273a
63.
Figer A, Louvet C, Homerin M, et al. Analysis of prognostic factors of overall survival in the randomized trial of bimonthly leucovorin and 5-fluorouracil regimen (LV5FU2) with or without oxaliplatin in advanced colorectal cancer [abstract no. 918]. Proc Am Soc Clin Oncol 1999; 18: 239a
64.
De Gramont A, Vignoud J, Tournigand C, et al. Oxaliplatin with high-dose leucovorin and 5-fluorouracil 48-hour continuous infusion in pretreated metastatic colorectal cancer. Eur J Cancer 1997; 33(2): 214–9PubMedCrossRef
65.
Andre T, Louvet C, Raymond E, et al. Bimonthly high-dose leucovorin, 5-fluorouracil infusion and oxaliplatin (FOLFOX3) for metastatic colorectal cancer resistant to the same leucovorin and 5-fluorouracil regimen. Ann Oncol 1998; 9(11): 1251–3PubMedCrossRef
66.
De Gramont A, Maindrault-Goebel F, Louvet C, et al. Evaluation of oxaliplatin dose-intensity with the bimonthly 48h leucovorin and 5-fluorouracil regimens (FOLFOX) in pretreated metastatic colorectal cancer [abstract no. 1018]. Proc Am Soc Clin Oncol 1999; 18: 265a
67.
Maindrault-Goebel F, De Gramont A, Louvet C, et al. Highdose oxaliplatin with the simplified 48h bimonthly leucovorin and 5-fluorouracil (5FU) regimen in pretreated metastatic colorectal cancer (FOLFOX) [abstract no. 1017]. Proc Am Soc Clin Oncol 1999; 18: 265a
68.
Van Cutsem E, Szanto J, Roth A, et al. Evaluation of the addition of oxaliplatin to the same Mayo or German 5FU regimen in advanced refractory colorectal cancer [abstract no. 900]. Proc Am Soc Clin Oncol 1999: 234a
69.
Bleiberg H, Brienza S, Gerard B, et al. Oxaliplatin combined with a high dose, 24-hour continuous 5-FU infusion and folinic acid based regimen in patients with advanced colorectal cancer [abstract no. 925]. Proc Am Soc Clin Oncol 1999; 18: 241a
70.
Becouarn Y, Ychou M, Ducreux M, et al., Digestive Group of French Federation of Cancer Centers. Phase II trial of oxaliplatin as first-line chemotherapy in metastatic colorectal cancer patients. J Clin Oncol 1998; 16(8): 2739–44PubMed
71.
Diaz-Rubio E, Sastre J, Zaniboni A, et al. Oxaliplatin as single agent in previously untreated colorectal carcinoma patients: a phase II multicentric study. Ann Oncol 1998; 9(1): 105–8PubMedCrossRef
72.
Machover D, Diaz-Rubio E, de Gramont A, et al. Two consecutive phase II studies of oxaliplatin (L-OHP) for treatment of patients with advanced colorectal carcinoma who were resistant to previous treatment with fluoropyrimidines. Ann Oncol 1996; 7(1): 95–8PubMedCrossRef
73.
Wasserman E, Kalla S, Misset JL, et al. Oxaliplatin (L-OHP) and irinotecan (CPT-11) phase I/II studies: results in 5FU refractory (FR) colorectal cancer (CRC) patients (pts) [abstract no. 913]. Proc Am Soc Clin Oncol 1999; 18: 238a
74.
Aherne GW, Ward E, Lawrence N, et al. Comparison of plasma and tissue levels of ZD1694 (Tomudex), a highly polyglutamable quinazoline thymidylate synthase inhibitor, in preclinical models. Br J Cancer 1998; 77: 221–6PubMedCrossRef
75.
Cunningham D, Zalcberg JR, Rath U, et al., Tomudex Colorectal Cancer Study Group. Final results of a randomized trial comparing ‘Tomudex’ (raltitrexed) with 5-fluorouracil plus leucovorin in advanced colorectal cancer. Ann Oncol 1996; 7: 961–5PubMedCrossRef
76.
Cocconi G, Cunningham D, Van Cutsem E, et al., Tomudex Colorectal Cancer Study Group. Open, randomized, multicenter trial of raltitrexed versus fluorouracil plus high-dose leucovorin in patients with advanced colorectal cancer. J Clin Oncol 1998; 16: 2943–52PubMed
77.
Pazdur R, Vincent M. Raltitrexed (Tomudex) vs 5-fluorouracil + leucovorin (5-FU + LV) in patients with advanced colorectal cancer (ACC): results of a randomized multicenter North American trial [abstract no. 801]. Proc Am Soc Clin Oncol 1997; 16:228a
78.
Cunningham D, Zalcberg JR, Rath U, et al. ‘Tomudex’ (ZD-1694): results of a randomized trial in advanced colorectal cancer demonstrate efficacy and reduced mucositis and leukopenia. Eur J Cancer 1995; 31A: 1945–54PubMedCrossRef
79.
Horikoshi N, Aiba K, Kurihara M, et al. Phase II study of ‘Tomudex’ in chemotherapy pretreated patients with advanced colorectal cancer [abstract no. 988]. Proc Am Soc Clin Oncol 1999; 18: 257a
80.
Brunet R, Fonck M, Smith D, et al. Management of metastatic colorectal cancer (MCRC): results of a strategy with first line tomudex chemotherapy (CT) [abstract no. 1069]. Proc Am Soc Clin Oncol 1999; 18: 278a
81.
Maughan TS, James RD, Kerr D, et al. Preliminary results of a multicentre randomized trial comparing 3 chemotherapy regimens (de Gramont, Lokich and Raltitrexed) in metastatic colorectal cancer [abstract no. 1007]. Proc Am Soc Clin Oncol 1999; 18:262a
82.
Blackledge G. New developments in cancer treatment with the novel thymidylate synthase inhibitor raltitrexed (‘Tomudex’). Br J Cancer 1998; 77Suppl. 2: 29–37PubMedCrossRef
83.
Bertino J, Schwartz GK, Kemeny N, et al. Raltitrexed (‘Tomudex’) plus 5-fluorouracil: improved palliation as second line therapy in patients with metastatic colorectal cancer [abstract no. 949]. Proc Am Soc Clin Oncol 1999; 18: 247a
84.
Seitz JF, Douillard JY, Paillot B, et al. ‘Tomudex’ (Raltitrexed) plus oxaliplatin as first-line chemotherapy in metastatic colorectal cancer (MCRC) [abstract no. 986]. Proc Am Soc Clin Oncol 1999; 18: 257a
85.
Gottlinger HG, Funke I, Johnson JP, et al. The epithelial cell surface antigen 17-1A, a target for antibody-mediated tumor therapy: its biochemical nature, tissue distribution and recognition by different monoclonal antibodies. Int J Cancer 1986; 38(1): 47–53PubMedCrossRef
86.
Riethmuller G, Schneider-Gadicke E, Schlimok G, et al. Randomized trial of monoclonal antibody for adjuvant therapy of resected Dukes’ C colorectal carcinoma. Lancet 1994; 343(8907): 1177–83PubMedCrossRef
87.
Riethmuller G, Holz E, Schlimok G. Monoclonal antibody therapy for resected Dukes’ C colorectal cancer: seven-year outcome of a multicenter randomized trial. J Clin Oncol 1998; 16: 1788–94PubMed
88.
Hoover Jr HC, Brandhorst JS, Peters LC, et al. Adjuvant active specific immunotherapy for human colorectal cancer: 6.5-year median follow-up of a phase III prospectively randomized trial. J Clin Oncol 1993; 11(3): 390–9PubMed
89.
Harris J, Ryan L, Adams G, et al. Survival and relapse in adjuvant autologous tumour vaccine therapy for Dukes B and C colon cancer: EST 5283 [abstract no. 955]. Proc Am Soc Clin Oncol 1994; 13: 294
90.
Vermorken JB, Claessen AM, van Tinteren H, et al. Active specific immunotherapy for stage II and stage III human colon cancer: a randomized trial. Lancet 1999; 353(9150): 345–50PubMedCrossRef
91.
Woodlock T, Sahasrabudhe DM, Marquis DM, et al. Active specific immunotherapy for metastatic colorectal carcinoma: phase I study of an allogeneic cell vaccine plus low-dose interleukin-1 alpha. J Immunother 1999; 3: 251–9CrossRef
Metadata
Title
Progress in Colorectal Cancer Chemotherapy
How Far Have We Come, How Far to Go?
Authors
Melanie E. Royce
Dr Paulo M. Hoff
Richard Pazdur
Publication date
01-09-2000
Publisher
Springer International Publishing
Published in
Drugs & Aging / Issue 3/2000
Print ISSN: 1170-229X
Electronic ISSN: 1179-1969
DOI
https://doi.org/10.2165/00002512-200017030-00004

Other articles of this Issue 3/2000

Drugs & Aging 3/2000 Go to the issue

Review Article

Pharmacoeconomics of Influenza Vaccination in the Elderly

Review Article

Subarachnoid Haemorrhage

Review Article

Treatment and Outcomes for Elderly Patients with Small Cell Lung Cancer

Leading Article

Androgen Receptor-Blocking Agents

Disease Management

Early Parkinson’s Disease
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits