Current Clinical Trials

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Stage IV (old staging: Modified Astler-Coller D)

Stage IV rectal cancer denotes distant metastatic disease. Local regional approaches to treating liver metastases include hepatic resection and/or intraarterial administration of chemotherapy with implantable infusion ports or pumps. For patients with limited (3 or less) hepatic metastases, resection may be considered with 5-year survival rates of 20% to 40%.[1-7]Other local ablative techniques that have been used to manage liver metastases include cryosurgery, embolization, and interstitial radiation therapy.[8,9] For those patients with hepatic metastases deemed unresectable (due to such factors as location, distribution, and excess number), cryosurgical ablation has been associated with long term tumor control.[10] Prognostic variables that predict a favorable outcome for cryotherapy are similar to those for hepatic resection, and include low preoperative carcinoembryonic antigen level, absence of extrahepatic disease, negative margins, and lymph node negative primary.[11][Level of evidence: 3iiiA] Patients with limited pulmonary metastases, and patients with both pulmonary and hepatic metastases, may also be considered for surgical resection, with 5-year survival possible in highly selected patients.[7,12,13] The role of additional systemic therapy after potentially curative resection of liver metastases is uncertain. A trial of hepatic arterial floxuridine plus systemic fluorouracil (5-FU) plus leucovorin was shown to result in improved 2-year disease-free and overall survival (86% versus 72%, P=.03), but did not show a significant statistical difference in medial survival, compared to systemic 5-FU therapy alone.[14][Level of evidence: 1iiA] Further follow-up is required to confirm these findings and to determine whether more effective combination chemotherapy alone may provide similar results compared to hepatic intra-arterial therapy plus systemic treatment.

Hepatic intraarterial chemotherapy with floxuridine for liver metastases has produced higher overall response rates but no improvement in survival when compared to systemic chemotherapy.[15-20] Controversy regarding the efficacy of regional chemotherapy has led to initiation of a large multicenter phase III trial (CALGB-9481) of hepatic arterial infusion versus systemic chemotherapy. Several studies show increased local toxic effects with hepatic infusional therapy, including liver function abnormalities and fatal biliary sclerosis.

In stage IV and recurrent rectal cancer, chemotherapy has been used for palliation with 5-FU-based treatment and is considered to be standard therapy.[21-23] 5-FU has been shown to be more cytotoxic, with increased response rates but with variable effects on survival, when modulated by leucovorin [24-30] or methotrexate.[31,32] Randomized clinical trials show that interferon alfa appears to add toxic effects but no clinical benefit to 5-FU therapy.[33,34] Continuous-infusion 5-FU regimens have also resulted in increased response rates in some studies, with a modest benefit in median survival.[35] The benefits of continuous-infusion 5-FU compared to bolus regimens have been summarized in a meta-analysis.[36] Oral regimens using prodrugs of 5-FU or inhibitors of dihydropyrimidine dehydrogenase (DPD) pharmacologically simulate continuous infusion and are under clinical evaluation.[37] The choice of a 5-FU-based chemotherapy regimen for an individual patient should be based on known response rates and toxic effects profile of the chosen regimen, as well as cost and quality-of-life issues.[38,39] In a meta-analysis of 1,219 patients in randomized trials where patients were assigned to receive 5-FU with or without leucovorin via either continuous infusion or bolus, neutropenia was noted in 4% of patients who received continuous infusion versus 31% of patients who received bolus and hand-foot syndrome was found in 34% of patients who received continuous infusion versus 13% of patients who received bolus. All other toxic effects were noted with similar frequency and severity, regardless of continuous infusion or bolus administration.[40]

DPD is the rate-limiting enzyme in the degradation pathway for 5-FU. While genetic polymorphism commonly results in considerable individual variability in levels of this enzyme, between 0.5% and 3% of the population are severely DPD deficient. Severe mucositis, neutropenia, diarrhea, and cerebellar dysfunction can result in toxic deaths among patients who are DPD deficient. Standard testing for DPD deficiency is not widely available, but one study found that patients with a pretreatment ratio of dihydrouracil to uracil of 1.8 or less were at risk of increased 5-FU toxic effects.[41-43]

Irinotecan (CPT-11) is a topoisomerase-I inhibitor with a 10% to 20% partial response rate in patients with metastatic rectal cancer, in patients who have received no prior chemotherapy, and in patients progressing on 5-FU therapy.[44,45] It is now considered standard therapy for patients with stage IV disease who do not respond to or progress on 5-FU.[46]

CPT-11 has been compared to either retreatment with 5-FU or best supportive care in a pair of randomized European trials of patients with colorectal cancer refractory to 5-FU.[47,48][Level of evidence: 1iiA,1iiC]

Two phase III prospective randomized, controlled trials were designed to evaluate the combination of 5-FU, leucovorin, and CPT-11 to 5-FU and leucovorin alone. The first of these trials compared the bolus 5-FU, leucovorin, and CPT-11 to bolus 5-FU and leucovorin alone and to CPT-11; the primary endpoint was progression-free survival.[49] The trial demonstrated significant benefit in terms of confirmed response rates, time-to-tumor progression, and overall survival.[49][Level of evidence: 1iiA] The combination treatment showed confirmed responses in 39% of patients, compared with 21% in patients treated with 5-FU and leucovorin alone and 18% in patients treated with CPT-11. This benefit was highly significant in favor of the combination. In addition, time-to-tumor progression was significantly prolonged with the combination (7.0 vs. 4.3 months, P = .004). Median survival was also improved with the combination; median survival was 14.8 months for patients on the combination arm and 12.6 months for patients on the 5-FU and leucovorin arm (P = .042).

The second pivotal trial of combination chemotherapy with CPT-11 compared 2 different regimens of infusional 5-FU and folinic acid (either the AIO [Arbeitsgemeinschaft Internische Onkologie] or the deGramont regimen).[50] Either weekly or biweekly CPT-11 was administered according to the schedule of the infusional 5-FU. This trial also demonstrated improvements in response rate, time-to-tumor progression, and median survival. For the most important endpoint, median survival, the combination arm was associated with a median survival of 17.4 months, compared with 14.1 months for the 5-FU and folinic acid arm (P = .032).[50][Level of evidence: 1iiA] A combined analysis of the survival advantages seen in these two trials was presented at the 2000 American Society of Clinical Oncology meeting.[51] The combined survival for the combination of CPT-11, 5-FU, and leucovorin was 15.9 months, compared to 13.3 months for the non-CPT-11 regimen (P = .003). This represents a survival hazard ratio of 0.79.

Another drug, raltitrexed (Tomudex), is a specific thymidylate synthase inhibitor that has demonstrated activity similar to that of bolus 5-FU and leucovorin.[52][Level of evidence: 1iiA];[53] A number of other drugs are undergoing evaluation for the treatment of rectal cancer.[54]

Oxaliplatin, alone or combined with 5-FU and leucovorin, has shown promising activity in previously treated and untreated patients with metastatic colorectal cancer and in patients with 5-FU refractory disease.[55-57] One multicenter trial reported a response rate of 21%, a median progression-free survival of 5 months, and a median survival of 11 months.[58] Overall survival from the start of first-line chemotherapy was 19 months. In this trial, oxaliplatin was given first, followed by 48-hour infusion of 5-FU, with short leucovorin infusion.

The data and safety monitoring committees of the cooperative groups conducting studies comparing the value of 5-FU/leucovorin/CPT-11 to 5-FU/leucovorin in the adjuvant setting, and comparing the value to 5-FU/leucovorin/oxaliplatin or oxaliplatin/CPT-11 in the advanced disease setting, have suspended accrual to these trials because of an unexpectedly high death rate on the 5-FU/leucovorin/CPT-11 arms.[59] This 3-drug regimen appears to be more toxic than initially reported. The majority of deaths in both studies were observed in the first 60 days, usually during the first chemotherapy cycle. This may imply increased sensitivity in a minority of patients, possibly based on genetic differences in key steps in the metabolic activation/deactivation of irinotecan, 5-FU, or both agents. Additional analyses may provide guidance in dose adjustment for the initial cycle and/or in patient selection. For the present, the use of this regimen should be accompanied by careful attention to early signs of diarrhea, dehydration, neutropenia, or other toxic effects, especially during the first chemotherapy cycle.

Standard treatment options:

1. Surgical resection/anastomosis or bypass of obstructing lesions in selected cases or resection for palliation.[60]
2. Surgical resection of isolated metastases (liver, lung, ovaries).[1,3,15,61-64]
3. Chemoradiation for local palliation.[65,66]
4. Chemotherapy alone for distant disease after resection of local disease.
5. Clinical trials evaluating new drugs and biologic therapy.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage IV rectal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References

1. Scheele J, Stangl R, Altendorf-Hofmann A: Hepatic metastases from colorectal carcinoma: impact of surgical resection on the natural history. Br J Surg 77 (11): 1241-6, 1990.  [PUBMED Abstract]
   
   
2. Steele G Jr, Bleday R, Mayer RJ, et al.: A prospective evaluation of hepatic resection for colorectal carcinoma metastases to the liver: Gastrointestinal Tumor Study Group Protocol 6584. J Clin Oncol 9 (7): 1105-12, 1991.  [PUBMED Abstract]
   
   
3. Scheele J, Stangl R, Altendorf-Hofmann A, et al.: Indicators of prognosis after hepatic resection for colorectal secondaries. Surgery 110 (1): 13-29, 1991.  [PUBMED Abstract]
   
   
4. Pedersen IK, Burcharth F, Roikjaer O, et al.: Resection of liver metastases from colorectal cancer. Indications and results. Dis Colon Rectum 37 (11): 1078-82, 1994.  [PUBMED Abstract]
   
   
5. Harmon KE, Ryan JA Jr, Biehl TR, et al.: Benefits and safety of hepatic resection for colorectal metastases. Am J Surg 177 (5): 402-4, 1999.  [PUBMED Abstract]
   
   
6. Fong Y, Cohen AM, Fortner JG, et al.: Liver resection for colorectal metastases. J Clin Oncol 15 (3): 938-46, 1997.  [PUBMED Abstract]
   
   
7. Headrick JR, Miller DL, Nagorney DM, et al.: Surgical treatment of hepatic and pulmonary metastases from colon cancer. Ann Thorac Surg 71 (3): 975-9; discussion 979-80, 2001.  [PUBMED Abstract]
   
   
8. Thomas DS, Nauta RJ, Rodgers JE, et al.: Intraoperative high-dose rate interstitial irradiation of hepatic metastases from colorectal carcinoma. Results of a phase I-II trial. Cancer 71 (6): 1977-81, 1993.  [PUBMED Abstract]
   
   
9. Ravikumar TS: Interstitial therapies for liver tumors. Surg Oncol Clin N Am 5 (2): 365-77, 1996.  [PUBMED Abstract]
   
   
10. Ravikumar TS, Kaleya R, Kishinevsky A: Surgical ablative therapy of liver tumors. Cancer: Principles and Practice of Oncology Updates 14 (3): 1-12, 2000. 
    
    
11. Seifert JK, Morris DL: Prognostic factors after cryotherapy for hepatic metastases from colorectal cancer. Ann Surg 228 (2): 201-8, 1998.  [PUBMED Abstract]
    
    
12. McAfee MK, Allen MS, Trastek VF, et al.: Colorectal lung metastases: results of surgical excision. Ann Thorac Surg 53 (5): 780-5; discussion 785-6, 1992.  [PUBMED Abstract]
    
    
13. Girard P, Ducreux M, Baldeyrou P, et al.: Surgery for lung metastases from colorectal cancer: analysis of prognostic factors. J Clin Oncol 14 (7): 2047-53, 1996.  [PUBMED Abstract]
    
    
14. Kemeny N, Huang Y, Cohen AM, et al.: Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer. N Engl J Med 341 (27): 2039-48, 1999.  [PUBMED Abstract]
    
    
15. Wagman LD, Kemeny MM, Leong L, et al.: A prospective, randomized evaluation of the treatment of colorectal cancer metastatic to the liver. J Clin Oncol 8 (11): 1885-93, 1990.  [PUBMED Abstract]
    
    
16. Kemeny N, Daly J, Reichman B, et al.: Intrahepatic or systemic infusion of fluorodeoxyuridine in patients with liver metastases from colorectal carcinoma. A randomized trial. Ann Intern Med 107 (4): 459-65, 1987.  [PUBMED Abstract]
    
    
17. Chang AE, Schneider PD, Sugarbaker PH, et al.: A prospective randomized trial of regional versus systemic continuous 5-fluorodeoxyuridine chemotherapy in the treatment of colorectal liver metastases. Ann Surg 206 (6): 685-93, 1987.  [PUBMED Abstract]
    
    
18. Rougier P, Laplanche A, Huguier M, et al.: Hepatic arterial infusion of floxuridine in patients with liver metastases from colorectal carcinoma: long-term results of a prospective randomized trial. J Clin Oncol 10 (7): 1112-8, 1992.  [PUBMED Abstract]
    
    
19. Reappraisal of hepatic arterial infusion in the treatment of nonresectable liver metastases from colorectal cancer. Meta-Analysis Group in Cancer. J Natl Cancer Inst 88 (5): 252-8, 1996.  [PUBMED Abstract]
    
    
20. Kemeny N, Cohen A, Seiter K, et al.: Randomized trial of hepatic arterial floxuridine, mitomycin, and carmustine versus floxuridine alone in previously treated patients with liver metastases from colorectal cancer. J Clin Oncol 11 (2): 330-5, 1993.  [PUBMED Abstract]
    
    
21. Moertel CG: Chemotherapy for colorectal cancer. N Engl J Med 330 (16): 1136-42, 1994.  [PUBMED Abstract]
    
    
22. Schmoll HJ, Büchele T, Grothey A, et al.: Where do we stand with 5-fluorouracil? Semin Oncol 26 (6): 589-605, 1999.  [PUBMED Abstract]
    
    
23. Grothey A, Schmoll HJ: New chemotherapy approaches in colorectal cancer. Curr Opin Oncol 13 (4): 275-86, 2001.  [PUBMED Abstract]
    
    
24. 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 9 (11): 1967-72, 1991.  [PUBMED Abstract]
    
    
25. Valone FH, Friedman MA, Wittlinger PS, et al.: Treatment of patients with advanced colorectal carcinomas with fluorouracil alone, high-dose leucovorin plus fluorouracil, or sequential methotrexate, fluorouracil, and leucovorin: a randomized trial of the Northern California Oncology Group. J Clin Oncol 7 (10): 1427-36, 1989.  [PUBMED Abstract]
    
    
26. Petrelli N, Douglass HO Jr, 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 7 (10): 1419-26, 1989.  [PUBMED Abstract]
    
    
27. Erlichman C, Fine S, Wong A, et al.: A randomized trial of fluorouracil and folinic acid in patients with metastatic colorectal carcinoma. J Clin Oncol 6 (3): 469-75, 1988.  [PUBMED Abstract]
    
    
28. Doroshow JH, Multhauf P, Leong L, et al.: Prospective randomized comparison of fluorouracil versus fluorouracil and high-dose continuous infusion leucovorin calcium for the treatment of advanced measurable colorectal cancer in patients previously unexposed to chemotherapy. J Clin Oncol 8 (3): 491-501, 1990.  [PUBMED Abstract]
    
    
29. 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 12 (1): 14-20, 1994.  [PUBMED Abstract]
    
    
30. Jäger E, Heike M, Bernhard H, et al.: Weekly high-dose leucovorin versus low-dose leucovorin combined with fluorouracil in advanced colorectal cancer: results of a randomized multicenter trial.Study Group for Palliative Treatment of Metastatic Colorectal Cancer Study Protocol 1. J Clin Oncol 14 (8): 2274-9, 1996.  [PUBMED Abstract]
    
    
31. Meta-analysis of randomized trials testing the biochemical modulation of fluorouracil by methotrexate in metastatic colorectal cancer. Advanced Colorectal Cancer Meta-Analysis Project. J Clin Oncol 12 (5): 960-9, 1994.  [PUBMED Abstract]
    
    
32. Blijham G, Wagener T, Wils J, et al.: Modulation of high-dose infusional fluorouracil by low-dose methotrexate in patients with advanced or metastatic colorectal cancer: final results of a randomized European Organization for Research and Treatment of Cancer Study. J Clin Oncol 14 (8): 2266-73, 1996.  [PUBMED Abstract]
    
    
33. 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 14 (10): 2682-7, 1996.  [PUBMED Abstract]
    
    
34. Greco FA, Figlin R, York M, et al.: Phase III randomized study to compare interferon alfa-2a in combination with fluorouracil versus fluorouracil alone in patients with advanced colorectal cancer. J Clin Oncol 14 (10): 2674-81, 1996.  [PUBMED Abstract]
    
    
35. Hansen RM, Ryan L, Anderson T, et al.: Phase III study of bolus versus infusion fluorouracil with or without cisplatin in advanced colorectal cancer. J Natl Cancer Inst 88 (10): 668-74, 1996.  [PUBMED Abstract]
    
    
36. Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. Meta-analysis Group In Cancer. J Clin Oncol 16 (1): 301-8, 1998.  [PUBMED Abstract]
    
    
37. Hoff PM, Royce M, Medgyesy D, et al.: Oral fluoropoyrimidines. Semin Oncol 26 (6): 640-6, 1999.  [PUBMED Abstract]
    
    
38. 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 13 (6): 1303-11, 1995.  [PUBMED Abstract]
    
    
39. Twelves C, Boyer M, Findlay M, et al.: Capecitabine (Xeloda) improves medical resource use compared with 5-fluorouracil plus leucovorin in a phase III trial conducted in patients with advanced colorectal carcinoma. Eur J Cancer 37 (5): 597-604, 2001.  [PUBMED Abstract]
    
    
40. Toxicity of fluorouracil in patients with advanced colorectal cancer: effect of administration schedule and prognostic factors. Meta-Analysis Group In Cancer. J Clin Oncol 16 (11): 3537-41, 1998.  [PUBMED Abstract]
    
    
41. Gamelin E, Boisdron-Celle M, Guérin-Meyer V, et al.: Correlation between uracil and dihydrouracil plasma ratio, fluorouracil (5-FU) pharmacokinetic parameters, and tolerance in patients with advanced colorectal cancer: A potential interest for predicting 5-FU toxicity and determining optimal 5-FU dosage. J Clin Oncol 17 (4): 1105, 1999.  [PUBMED Abstract]
    
    
42. Morrison GB, Bastian A, Dela Rosa T, et al.: Dihydropyrimidine dehydrogenase deficiency: a pharmacogenetic defect causing severe adverse reactions to 5-fluorouracil-based chemotherapy. Oncol Nurs Forum 24 (1): 83-8, 1997 Jan-Feb.  [PUBMED Abstract]
    
    
43. Diasio RB: Clinical implications of dihydropyrimidine dehydrogenase inhibition. Oncology (Huntingt) 13 (7 Suppl 3): 17-21, 1999.  [PUBMED Abstract]
    
    
44. 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 14 (4): 1128-35, 1996.  [PUBMED Abstract]
    
    
45. Conti JA, Kemeny NE, Saltz LB, et al.: Irinotecan is an active agent in untreated patients with metastatic colorectal cancer. J Clin Oncol 14 (3): 709-15, 1996.  [PUBMED Abstract]
    
    
46. Cunningham D, Pyrhonen S, James RD, et al.: A phase III multicenter randomized study of CPT-11 versus supportive care (SC) alone in patients (Pts) with 5FU-resistant metastatic colorectal cancer (MCRC). [Abstract] Proceedings of the American Society of Clinical Oncology 17: A-1, 1a, 1998. 
    
    
47. 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 352 (9138): 1407-12, 1998.  [PUBMED Abstract]
    
    
48. Cunningham D, Pyrhönen S, James RD, et al.: Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. Lancet 352 (9138): 1413-8, 1998.  [PUBMED Abstract]
    
    
49. Saltz LB, Cox JV, Blanke C, et al.: Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med 343 (13): 905-14, 2000.  [PUBMED Abstract]
    
    
50. 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 355 (9209): 1041-7, 2000.  [PUBMED Abstract]
    
    
51. Saltz LB, Douillard J, Pirotta N, et al.: Combined analysis of two phase III randomized trials comparing irinotecan (C), fluorouracil (F), leucovorin (L) vs F alone as first-line therapy of previously untreated metastatic colorectal cancer (MCRC). [Abstract] Proceedings of the American Society of Clinical Oncology 19: A-938, 242a, 2000. 
    
    
52. Cunningham D: Mature results from three large controlled studies with raltitrexed ('Tomudex'). Br J Cancer 77 (Suppl 2): 15-21, 1998.  [PUBMED Abstract]
    
    
53. 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. Tomudex Colorectal Cancer Study Group. J Clin Oncol 16 (9): 2943-52, 1998.  [PUBMED Abstract]
    
    
54. Von Hoff DD: Promising new agents for treatment of patients with colorectal cancer. Semin Oncol 25 (5 Suppl 11): 47-52, 1998.  [PUBMED Abstract]
    
    
55. 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 33 (2): 214-9, 1997.  [PUBMED Abstract]
    
    
56. Bleiberg H, de Gramont A: Oxaliplatin plus 5-fluorouracil: clinical experience in patients with advanced colorectal cancer. Semin Oncol 25 (2 Suppl 5): 32-9, 1998.  [PUBMED Abstract]
    
    
57. Cvitkovic E, Bekradda M: Oxaliplatin: a new therapeutic option in colorectal cancer. Semin Oncol 26 (6): 647-62, 1999.  [PUBMED Abstract]
    
    
58. André T, Bensmaine MA, Louvet C, et al.: Multicenter phase II study of bimonthly high-dose leucovorin, fluorouracil infusion, and oxaliplatin for metastatic colorectal cancer resistant to the same leucovorin and fluorouracil regimen. J Clin Oncol 17 (11): 3560-8, 1999.  [PUBMED Abstract]
    
    
59. Sargent DJ, Niedzwiecki D, O'Connell MJ, et al.: Recommendation for caution with irinotecan, fluorouracil, and leucovorin for colorectal cancer. N Engl J Med 345 (2): 144-5; discussion 146, 2001.  [PUBMED Abstract]
    
    
60. Wanebo HJ, Koness RJ, Vezeridis MP, et al.: Pelvic resection of recurrent rectal cancer. Ann Surg 220 (4): 586-95; discussion 595-7, 1994.  [PUBMED Abstract]
    
    
61. Adson MA, van Heerden JA, Adson MH, et al.: Resection of hepatic metastases from colorectal cancer. Arch Surg 119 (6): 647-51, 1984.  [PUBMED Abstract]
    
    
62. Coppa GF, Eng K, Ranson JH, et al.: Hepatic resection for metastatic colon and rectal cancer. An evaluation of preoperative and postoperative factors. Ann Surg 202 (2): 203-8, 1985.  [PUBMED Abstract]
    
    
63. Taylor M, Forster J, Langer B, et al.: A study of prognostic factors for hepatic resection for colorectal metastases. Am J Surg 173 (6): 467-71, 1997.  [PUBMED Abstract]
    
    
64. Jaeck D, Bachellier P, Guiguet M, et al.: Long-term survival following resection of colorectal hepatic metastases. Association Française de Chirurgie. Br J Surg 84 (7): 977-80, 1997.  [PUBMED Abstract]
    
    
65. Wong CS, Cummings BJ, Brierley JD, et al.: Treatment of locally recurrent rectal carcinoma--results and prognostic factors. Int J Radiat Oncol Biol Phys 40 (2): 427-35, 1998.  [PUBMED Abstract]
    
    
66. Crane CH, Janjan NA, Abbruzzese JL, et al.: Effective pelvic symptom control using initial chemoradiation without colostomy in metastatic rectal cancer. Int J Radiat Oncol Biol Phys 49 (1): 107-16, 2001.  [PUBMED Abstract]
    
    

Back to Top

< Previous Section  |  Next Section >