Abstract
In Europe and the US >300 000 cases of advanced colorectal cancer are diagnosed each year, and it is the third most common type of cancer after breast/prostate and lung cancers. The lifetime risk of developing colorectal cancer increases with genetic predisposition or a family history of colorectal cancer. The 5-year survival rate varies depending on the stage at which colorectal cancer is diagnosed. Advanced colorectal cancer (stage IV, Duke’s D) has a 5-year survival rate of <5%.
Screening and early detection can significantly increase the likelihood of survival. Treatment of early colorectal cancer relies on surgery and/or chemotherapy. Patients with stage I to II (Duke’s A to B) colorectal cancer have a good prognosis, with a >70% survival rate at 5 years. While the management of advanced colorectal cancer also encompasses these options, treatment is largely palliative. Fluorouracil is currently the gold standard for treatment of advanced colorectal cancer. However, despite its widespread use it is associated with a relatively low tumor response rate (<15%), drug regimens are complex and toxicities are significant.
Raltitrexed, a specific thymidylate synthase inhibitor, has been approved for the treatment of advanced colorectal cancer. As first-line therapy it has similar efficacy to fluorouracil in terms of tumor response rates (approximately 14 to 19%) and overall survival duration (approximately 10 to 11 months), although disease progression may be sooner with raltitrexed. However, in an effort to further increase survival duration, raltitrexed has been administered concomitantly with fluorouracil or oxaliplatin therapy as first- or second-line therapy, with promising preliminary results.
In comparative clinical trials, leukopenia and mucositis were more commonly associated with fluorouracil than with raltitrexed monotherapy. In contrast, elevated transaminase levels, which were not clinically significant, and anemia were more common with the raltitrexed regimen.
Higher drug acquisition costs for raltitrexed than for fluorouracil are partially offset by reduced pharmacy resource utilization, lower drug administration costs and reduced costs relating to the management of chemotherapy-induced adverse events. Overall treatment-related costs were slightly higher for raltitrexed than for fluorouracil administered according to the Mayo regimen, but lower than either the Lokich or De Gramont regimens.
Early comparative quality-of-life assessments favoured raltitrexed over fluorouracil; however, comparisons at 15 weeks failed to show any clear preference in favor of either treatment. Palliative improvements occurred in patients who responded to treatment or those who had disease stabilization in both treatment groups.
Conclusions
Raltitrexed is a first-line treatment option for the management of advanced colorectal cancer and offers a more convenient administration regimen than traditional fluorouracil infusion regimens. Available data suggest that it may have lower overall treatment costs than some but not all fluorouracil regimens; however, formal cost-effectiveness comparisons (in terms of cost per clinical outcome) are not available. Preliminary results from trials of combination therapy with raltitrexed and either fluorouracil or oxaliplatin are promising; however, further data on raltitrexed combination therapy are necessary to better determine its place in the management of advanced colorectal cancer.
Similar content being viewed by others
References
Adjei AA. A review of the pharmacology and clinical activity of new chemotherapy agents for the treatment of colorectal cancer. Br J Clin Pharmacol 1999 Sep; 48: 265–77
Jackman AL, Boyle FT, Harrap KR. Tomudex (ZD1694): from concept to care, a programme in rational drug discovery. Invest New Drugs 1996; 14(3): 305–16
Taylor SC. Raltitrexed for advanced colorectal cancer: the story so far. Cancer Pract 2000 Jan–Feb; 8: 51–4
Gunasekara NS, Faulds D. Raltitrexed: a review of its pharmacological properties and clinical efficacy in the management of advanced colorectal cancer. Drugs 1998 Mar; 55: 423–35
Sobrero AF. The potential role of Tomudex in the treatment of advanced colorectal cancer. Tumori 1997 Mar–Apr; 83: 576–80
Rudy DR, Zdon MJ. Update on colorectal cancer. Am Fam Physician 2000; 61(6): 1759–70
Midgley R, Kerr D. Colorectal cancer [see comments]. Lancet 1999 Jan 30; 353: 391–9
Briskey EN, Pamies RJ. Colorectal cancer: update on recent advances and thier impact on screening protocols. J Natl Med Assoc 2000; 92(5): 222–30
Seifeldin R, Hantsch JJ. The economic burden associated with colon cancer in the United States. Clin Ther 1999 Aug; 21: 1370–9
Van-Cutsem E, Peeters M, Verslype C, et al. The medical treatment of colorectal cancer: actual status and new developments. Hepatogastroenterology 1999 Mar–Apr; 46: 709–16
Bleiburg H. Colorectal cancer-is there an alternative to 5-FU? Eur J Cancer 1997; 33(4): 536–41
Kuwada SK. Colorectal cancer 2000: education and screening are essential if outcomes are to improve. Postgrad Med 2000; 107(5): 96–107
Mushinski M. Variation in in-hospital charges for colorectal cancer treatment. Stat Bull Metrop Insur Co 1998 Jan–Mar; 79: 19–27
Peeters M, Haller DG. Therapy for early-stage colorectal cancer. Oncology Huntingt 1999 Mar; 13: 307–17
Bleiberg H. Role of chemotherapy for advanced colorectal cancer: new opportunities. Semin Oncol 1996 Feb; 23(1) Suppl. 3: 42–50
Jansman FGA, Sleijfer DT, Coenen JLLM, et al. Risk factors determining chemotherapeutic toxicity in patients with advanced colorectal cancer. Drug Saf 2000; 23(4): 255–78
Bodger K. Colorectal cancer. J R Coll Physicians Lond 2000; 34(2): 197–201
Shike M. Diet and lifestyle in the prevention of colorectal cancer: an overview. Am J Med 1999; 106 Suppl. 1A: 11S–5S
Troisi RJ, Freedman AN, Devesa SS. Incidence of colorectal carcinoma in the U.S.: an update of trends by gender, race, age, subsite, and stage, 1975–1994. Cancer 1999 Apr 15; 85: 1670–6
Schrag D, Weeks J. Costs and cost-effectiveness of colorectal cancer prevention and therapy. Semin Oncol 1999 Oct; 26: 561–8
Bond JH. Screening guidelines for colorectal cancer. Am J Med 1999 Jan 25; 106: 7S–10S
Ivanovich JL, Read TE, Ciske DJ, et al. A practical approach to familial and hereditary colorectal cancer. Am J Med 1999 Jul; 107: 68–77
Lee MI, Paffenbarger Jr RS, Hsieh C. Physical activity and risk of developing colorectal cancer among college alumni. J Natl Cancer Inst 1991; 83: 1324–9
Houlston RS, Murday V, Harocopos C, et al. Screening and genetic counselling for relatives of patients with colorectal cancer in a family cancer clinic. BMJ 2000; 301: 366–8
Dunlop MG. Colorectal cancer. BMJ 1997 Jun 28; 314: 1882–5
National Cancer Institute. Colon cancer. In: PDQ Information for healthcare professionals [online]. CancerNet; 2000 Nov. Available from: URL: http://www.cancernet.nci.nih.gov [Accessed 2000 Sep 21]
Labianca R, Pessi MA, Zamparelli G. Treatment of colorectal cancer: current guidelines and future prospects for drug therapy. Drugs 1997 Apr; 53: 593–607
Bleiberg H. Continuing the fight against advanced colorectal cancer: new and future treatment options. Anticancer Drugs 1998 Jan; 9: 18–28
Karapetis CS, Yip D, Harper PG. The treatment of metastatic colorectal cancer. Int J Clin Pract 1999; 53(4): 287–94
Koehne CH, Midgley R, Seymour M, et al. Advanced colorectal cancer: which regimens should we recommend? Ann Oncol 1999; 10: 877–82
Gordon NLM, Dawson AA, Bennett B, et al. Outcome in colorectal adenocarcinoma: two seven-year studies of a population. BMJ 1993; 307: 707–10
Papamichael D. The use of thymidylate synthase inhibitors in the treatment of advanced colorectal cancer: current status. Oncologist 1999; 4: 478–87
Nordic Gastrointestinal Tumor Adjuvant Therapy Group. Expectancy or primary chemotherapy in patients with advanced asymptomatic colorectal cancer: a randomized trial. J Clin Oncol 1992; 10: 904–11
Caponigro F, Avallone A, McLeod H, et al. Phase I and pharmacokinetic study of Tomudex combined with 5-fluorouracil plus levofolinic acid in advanced head and neck cancer and colorectal cancer. Clin Cancer Res 1999; 5: 3948–55
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
Summerhayes M, Wanklyn SJ, Shakespeare RA, et al. Reduced pharmacy resource utilization associated with raltitrexed treatment of advanced colorectal cancer. J Oncol Pharm Practice 1997; 3(1): 24–30
Ledermann JA, Maughan TS, James RD, et al. Preliminary results of a multicentre randomised trial comparing 3 chemotherapy regimens (de Gramont, Lokich and raltitrexed) in metastatic colorectal cancer [abstract]. Br J Cancer 1999 Jul; 80 Suppl. 2: 20
AstraZeneca. Raltitrexed combination therapy in advanced colorectal cancer. Clinical Investigators Monograph. Cheshire: Astra Zeneca, 2000 Oct
Sato A, Kurihara M, Horikoshi N, et al. Phase II study of raltitrexed (Tomudex®) in chemotherapy-pretreated patients with advanced colorectal cancer. Anticancer Drugs 1999 Sep; 10: 741–8
Raltitrexed: a convenient alternative for advanced colorectal cancer. Drug Ther Perspect 1998 Aug 17; 12 Suppl. 4: 1-5
Culy C, Clemett D, Wiseman L. Oxaliplatin: a review of its pharmacological properties and clinical efficacy in metastatic colorectal cancer and its potential in other malignancies. Drugs 2000; 60(4): 895–924
Oxaliplatin.. In: BNF 40 Sep 2000. British Medical Association and Royal Pharmaceutical Society of Great Britian. London: Bemrose Security Printing, 2000: 400
Douillard JY, Cunningham D, Roth AD, et al. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet 2000 Mar 25; 355: 1041–7
Saltz LB, Cox JV, Blanke C, et al. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. N Engl J Med 2000; 343(13): 905–14
Van Cutsem E, Cunningham D, Ten Bokkel Huinink WW, et al. Clinical activity and benefit of irinotecan (CPT-11) in patients with colorectal cancer truly resistant to 5-fluorouracil (5-FU). Eur J Cancer 1999; 35(1): 54–9
Giacchetti S, Perpoint B, Ziadani R, et al. Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. J Clin Oncol 2000; 18(1): 136–47
de Gramont A, Figer A, Seymour M, et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 2000; 18(16): 2938–47
Blackledge G. New developments in cancer treatment with the novel thymidylate synthase inhibitor raltitrexed (’Tomudex’). Br J Cancer 1998; 77 Suppl. 2: 29–37
Jackman AL, Kimbell R, Ford HER. Combination of raltitrexed with other cytotoxic agents: rationale and preclinical observations. Eur J Cancer 1999 Mar; 35 (Part A) Suppl. 1: S3–8
Schwartz GK, Harstrick A, Baron MG. Raltitrexed (Tomudex™) in combination with 5-fluorouracil for the treatment of patients with advanced colorectal cancer: preliminary results from phase I clinical trials. Eur J Cancer 1999; 35 Suppl. 1: S9–13
Cunningham D, Zalcberg JR, Rath U, et al. Final results of a randomised trial comparing ‘Tomudex’ (raltitrexed) with 5-fluorouracil plus leucovorin in advanced colorectal cancer. Ann Oncol 1996 Nov; 7: 961–5
Pazdur R, Vincent M. Raltitrexed (Tomudex) versus 5-fluorouracil and 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 May 17–20; 16: 228a
Cocconi G, Cunningham D, Van Cutsem E, et al. Open, randomized, multicenter trial of raltitrexed versus fluorouracil plus high-dose leucovorin in patients with advanced colorectal cancer. J Clin Oncol 1998 Sep; 16: 2943–52
Maughan T, James R, Kerr D, et al. Excess treatment related deaths and impaired quality of life show raltitrexed is inferior to infusional 5FU regimens in the palliative chemotherapy of advanced colorectal cancer (CRC): final results of MRC CR06 [[abstract]]. Ann Oncol 2000; 11 Suppl. 4: 43
Van Cutsem E. Future developments with ‘Tomudex’ (raltitrexed). Anticancer Drugs 1997; 8 Suppl. 2: S33–8
Van-Cutsem E. Raltitrexed (Tomudex) in combination treatment for colorectal cancer: new perspectives. Eur J Cancer 1999 Mar; 35 Suppl. 1: S1–2
Cascinu S, Silva RR, Labianca R, et al. A phase II study of tomudex alternated with methotrexate, 5-fluorouracil, leucovorin in first-line chemotherapy of metastatic colorectal cancer. Ann Oncol 1999 Aug; 10: 985–7
Kornek GV, Ulrich Pur H, Raderer M, et al. Oxaliplatin + Tomudex in patients with advanced colorectal cancer (cc): a disease-oriented phase I/II trial [abstract]. Onkologie 1999 Aug; 22 Suppl. 1: 80
Cambridge Laboratories. Fluorouracil. In: ABPI compendium of data sheets and summaries of product characteristics. London: Datapharm Publications Limited, 1996-1997: 185–6
AstraZeneca. Full prescribing information for ‘Tomudex’ (raltitrexed). Cheshire: AstraZeneca, 2000 Aug
Maughan TS, James RD, Kerr D, et al. Preliminary results of a multicentre randomised trial comparing 3 chemotherapy regimens (de Gramont, Lokich and raltitrexed) in metastatic colorectal cancer, [abstract no. 1007] Atlanta (GA): American Society of Clinical Oncology, 1999
Mel J, Feliu J, Camps C. ’Tomudex’ (raltitrexed) in elderly patients with advanced colorectal cancer (ACC): an effective palliative treatment [abstact no. 1000]. American Society of Clinical Oncology; 36th Annual Meeting, 2000, May 20–23, New Orleans
Douillard JY, Michel P, Gamelin E, et al. Raltitrexed (Tomudex) plus oxaliplatin: an active combination for first-line chemotherapy in patients with metastatic colorectal cancer [abstract]. 36th Annual Meeting of the American Society of Clinical Oncology; 2000: New Orleans LA, 250
Harstrick A, Mayer S, Hilger R, et al. Combination therapy with infusional 5-FU and ‘Tomudex’ for patients (pts) with advanced colorectal cancer- a phase I study. Ann Oncol 1998; 9 Suppl. 4: 35
Scheithaur W, Kornek G, Ulrich-Pur H. Promising therapeutic potential of oxaliplatin + raltitrexed in patients with advanced colorectal cancer (ACC): results of a phase I/II trial [abstract no. 997]. American Society of Clinical Oncology; 6th Annual Meeting, 2000 May 20–23, New Orleans
Fizazi K, Ducreux M, Ruffié P, et al. Phase I, dose-finding, and pharmacokinetic study of raltitrexed combined with oxaliplatin in patients with advanced cancer. J Clin Oncol 2000; 18(11): 2293–300
Mayer S, Vanhoefer U, Hilger R, et al. Extended phase I study of raltitrexed and infusional 5-FU in patients with metastatic colorectal cancer [abstract no. 1169]. Proceedings of the 36th Annual Meeting of the American Society of Clinical Oncology, 2000, May 20–23, New Orleans
Schwartz GK, Bertino J, Kemeny N, et al. Phase I trial of sequential raltitrexed (’Tomudex’) followed by 5-FU in patients with advanced colorectal cancer [abstract no.977]. Proceedings of the 36th Annual Meeting of the American Society of Clinical Oncology, 2000, May 20–23, New Orleans
Osterlund P, Elomaa I, Virkkunen P, et al. A phase II study of raltitrexed (’Tomudex’) combined with carmofur in metastatic CRC [abstract no. 1104]. Proceedings of the 36th Annual Meeting of the American Society of Clinical Oncology, 2000, May 20–23, New Orleans
Carnaghi C, Zucali P, Rimassa L. Promising activity of irinotecan (CPT11) and raltitrexed (ZD1694) as first line chemotherapy in metastatic cancer (MCC) [abstract no. 1211]. American Society of Clinical Oncology; 6th Annual Meeting, 2000 May 20–23, New Orleans
Nobile M, Gozza A, Heouaine A, et al. Irinotecan (CPT11) and raltitrexed (Tomudex) in advanced colorectal cancer: a phase II study [abstract no. 1220]. American Society of Clinical Oncology; 6th Annual Meeting, 2000 May 20–23, New Orleans
Ford HER, Cunningham D, Ross PJ, et al. Phase I study of irinotecan and raltitrexed in patients with advanced gastrointestinal tract adenocarcinoma. BrJ Cancer 2000; 18(2): 146–52
Michels JE, Harvey M, Darby A, et al. The combination of raltitrxed (Tomudex) and mitomycin-C in the treatment of advanced colorectal cancer: a phase II study. Br J Cancer 2000 Jul; 83 Suppl. 1: 46
James R, Price P, Valentini V. Raltitrexed (Tomudex™) concomitant with radiotherapy as adjuvant treatment for patients with rectal cancer: preliminary results of phase I studies. Eur J Cancer 1998; 35 Suppl. 1: S19–22
Valentini V, Smaniotto D, Fiorentino G, et al. Dose finding study of Tomudex concomitantly administered with perioperative radiotherapy in stage II-III resectable rectal cancer. Ann Oncol 1998; 9 Suppl. 4: 44
James R, Price P, Valentini V. Raltitrexed (Tomudex™) concomitant with radiotherapy as adjuvant treatment for patients with rectal cancer: preliminary results of phase I studies. Eur J Cancer A 1999 Mar; 35 Suppl. 1: 19–22
Botwood N, James R, Vernon C, et al. Raltitrexed (’Tomudex’) and radiotherapy can be combined as postoperative treatment for rectal cancer. Ann Oncol 2000; 11(8): 1023–8
James RD, Vernon C, Price P, et al. A pilot study of ‘Tomudex’ plus radiotherapy in patients with inoperable/recurrent rectal cancer. Ann Oncol 1998; 9 Suppl. 4: 41–2
Price P, James R, Smith M. ’Tomudex’ (raltitrexed) plus radiotherapy as post-operative treatment or palliative treatment for patients with rectal cancer: phase I studies [abstract no. 223]. Eur J Cancer 1999; 35 Suppl. 4: S72
Candido P, Piazza E, Cattaneo MT, et al. Raltitrexed in the treatment of advanced colorectal cancer [abstract]. Tumori 1998 Sep–Oct; 84 Suppl. 1: 124
Zalcberg J. Overview of the tolerability of ‘Tomudex’ (raltitrexed): collective clinical experience in advanced colorectal cancer. Anticancer Drugs 1997; 8 Suppl. 2: S17–22
Cunningham D, Zalcberg JR, Rath U, et al. ’Tomudex’ (ZD1694): results of a randomised trial in advanced colorectal cancer demonstrate efficacy and reduced mucositis and leucopenia. Eur J Cancer 1995; 31A(12): 1945–54
AstraZeneca. Tomudex technical monograph: International edition. Cheshire: AstraZeneca, 2000 Aug
Drug-company decision to end cancer trial [editorial]. Lancet 1999 Sept 25; 354 (9184): 1045
Wils J. The establishment of a large collaborative trial programme in the adjuvant treatment of colon cancer. Br J Cancer 1998; 77 Suppl. 2: 23–8
Ford HER, Cunningham D. Safety of raltitrexed [letter]. Lancet 1999 Nov 20; 354: 1824–5
Kerr D. Safety of raltitrexed [letter]. Lancet 1999 Nov 20; 354: 1825
Young A, Topham C, Moore J, et al. A patient preference study comparing raltitrexed (’Tomudex’) and bolus or infusional 5-fluorouracil regimens in advanced colorectal cancer: influence of side-effects and administration attributes. Eur J Cancer Care 1999 Sep; 8: 154–61
Ross P, Heron J, Cunningham D. Cost of treating advanced colorectal cancer: a retrospective comparison of treatment regimens. Eur J Cancer A 1996; 32A Suppl. 5: S13–7
Groener MGH, van Ineveld BM, Byttebier G, et al. An economic evaluation of Tomudex (raltitrexed) and 5-fluorouracil plus leucovorin in advanced colorectal cancer. Anticancer Drugs 1999 Mar; 10: 283–8
Kerr D, O’Connor KM. An economic comparison of the net clinical benefit and treatment costs of raltitrexed and 5-fluorouracil + leucovorin (Mayo regimen) in advanced colorectal cancer. Journal of Drug Assessment 1999; 2: 295–304
Groener MGH, van Ineveld BM, Byttebier G, et al. Evaluation of relative costs of the cytostatic agents Tomudex® and 5-fluorouracil plus leucovorin as treatments for advanced colorectal cancer [abstract]. Eur J Cancer 1997 Nov; 33 (Part A) Suppl. 9: S4–5
Elliott R. An analysis of drug costs for the management of chemotherapy-related side effects in advanced colorectal cancer. A comparison between raltitrexed (’Tomudex’) and 5-fluorouracil plus folinic acid. J Oncol Pharm Pract 1996; 2(3): 186–90
Sculpher M, Palmer MK, Heyes A. Costs incurred by patients undergoing advanced colorectal cancer therapy: a comparison of raltitrexed and fluorouracil plus leucovorin. Pharmacoeconomics 2000 Apr; 17: 361–70
Cunningham D. Mature results from three large controlled studies with raltitrexed (’Tomudex’). Br J Cancer 1998; 77 Suppl. 2: 15–21
Anderson H, Palmer MK. Measuring quality of life: impact of chemotherapy for advanced colorectal cancer. Experience from two recent large phase III trials. Br J Cancer 1998; 77 Suppl. 2: 9–14
Author information
Authors and Affiliations
Corresponding author
Additional information
Various sections of the manuscript reviewed by: J. Bertino, Molecular Pharmacology and Therapeutics, Sloan-Kettering Institute for Cancer Research, New York, New York, USA; A. Jackman, CRC Centre for Cancer Therapeutics, The Institute of Cancer Research, Sutton, England; D.J. Kerr, CRC Institute for Cancer Studies, Clinical Research Block, University of Birmingham, Birmingham, England; R. Labianca, Division of Medical Oncology, S. Carlo Borromeo Hospital, Milan, Italy; D. Papamichael, Cyprus Oncology Centre, Nicosia, Cyprus; A. Sato, Department of Gastroenterology, Toyosu Hospital, Showa University School of Medicine, Tokyo, Japan; E. Van Cutsem, Department of Internal Medicine, University Hospital Gasthuisberg, Leuven, Belgium.
Data Selection
Sources: Medical literature published in any language since 1966 on Raltitrexed identified using Medline supplemented by AdisBase (a proprietary database of Adis International, Auckland, New Zealand). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.
Search strategy: AdisBase search terms were ‘Colorectal-cancer’ and (‘guideline’ or ‘guideline-utilisation’ or ‘practice-guideline’ or ‘disease-management-programmes’ or ‘treatment-algorithms’ or ‘reviews-on-treatment’ or ‘drug-evaluations’ or ‘epidemiology’ or ‘cost-of-illness’ or ‘pathogenesis’), or ‘Raltitrexed’ and (‘review’ or ‘clinical-study’). Medline search terms were ‘Colorectal-neoplasms and (‘guidelines’ or ‘decision-making’ or ‘health-policy’ or ‘managed-care-programs’ or ‘epidemiology’ or ‘outcome-assessment-health-care’ or ‘clinical-protocols’ or ‘guideline in pt’ or ‘practice-guideline in pt’), or ‘Raltitrexed’ and ‘review in pt’. Searches were last updated 26 March 2001.
Selection: Studies in patients with advanced colorectal cancer who received raltitrexed. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic, pharmacokinetic, pharmacoeconomic and epidemiological data are also included.
Index terms: colorectal cancer, ralitrexed, fluorouracil, disease management, review on treatment.
Rights and permissions
About this article
Cite this article
Matheson, A.J., Noble, S. Management of Colorectal Cancer. Dis-Manage-Health-Outcomes 9, 269–287 (2001). https://doi.org/10.2165/00115677-200109050-00004
Published:
Issue Date:
DOI: https://doi.org/10.2165/00115677-200109050-00004