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Rectal Cancer Treatment (PDQ®)

Stages II and III Rectal Cancer

Standard Treatment Options for Stages II and III Rectal Cancer

Standard treatment options for stages II and III rectal cancer include the following:

Surgery

Total mesorectal excision with either low anterior resection or abdominoperineal resection is usually performed for stages II and III rectal cancer before or after chemoradiation therapy.

Retrospective studies have demonstrated that some patients with pathological T3, N0 disease treated with surgery and no additional therapy have a very low risk of local and systemic recurrence.[1]

Preoperative chemoradiation therapy

Preoperative chemoradiation therapy has become the standard of care for patients with clinically staged T3 or T4 or node-positive disease, based on the results of several studies.

Evidence (preoperative chemoradiation therapy):

  1. The German Rectal Cancer Study Group (CAO/ARO/AIO-94 [Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society]) randomly assigned 823 patients with ultrasound-staged T3 or T4 or node-positive rectal cancer to either preoperative chemoradiation therapy or postoperative chemoradiation therapy (50.4 Gy in 28 daily fractions to the tumor and pelvic lymph nodes concurrent with infusional fluorouracil [5-FU] 1,000 mg/m2 daily for 5 days during the first and fifth weeks of radiation therapy).[2][Level of evidence: 1iA] All patients underwent total mesorectal excision and received four additional cycles of 5-FU-based chemotherapy.
    • The 5-year overall survival (OS) rates were 76% for preoperative chemoradiation therapy and 74% for postoperative chemoradiation therapy (P = .80). The 5-year cumulative incidence of local relapse was 6% for patients assigned to the preoperative chemoradiation therapy group and 13% for patients in the postoperative chemoradiation therapy group (P = .006).
    • Grade 3 or 4 acute toxic effects occurred in 27% of patients in the preoperative-treatment group and in 40% of patients in the postoperative-treatment group (P = .001); the corresponding rates of long-term toxic effects were 14% and 24%, respectively (P = .01).
    • The same number of patients underwent abdominoperineal resection in each arm. However, among the 194 patients with tumors that were determined by the surgeon before randomization to require an abdominoperineal excision, a statistically significant increase in sphincter preservation was achieved among patients who received preoperative chemoradiation therapy (P = .004). These results have now been updated with a median follow-up of 11 years.[3]
    • The 10-year OS was equivalent in both arms, (59.6% in the preoperative group vs. 59.9% in the postoperative group; P = .85). However, a local control benefit persists among patients treated with preoperative chemoradiation therapy compared with patients treated with postoperative chemoradiation therapy (10-year cumulative incidence of local relapse: 7.1% in the preoperative group vs. 10.1% in the postoperative group; P = .048). There were no significant differences detected for 10-year cumulative incidence of distant metastases or disease-free survival (DFS).[3]
    • Among the patients assigned to the postoperative chemoradiation therapy treatment arm, 18% actually had pathologically determined stage I disease and were overestimated by endorectal ultrasound to have T3 or T4 or N1 disease. A similar number of patients were possibly overtreated in the preoperative treatment group.
  2. The NSABP R-03 trial similarly compared preoperative versus postoperative chemoradiation therapy for patients with clinically staged T3 or T4 or node-positive rectal cancer. Chemotherapy consisted of 5-FU/leucovorin (LV) with 45 Gy in 25 fractions with a 5.4 Gy boost. Although the intended sample size was 900 patients, the study closed early because of poor accrual, with 267 patients.[4][Level of evidence: 1iiA]
    • With a median follow-up of 8.4 years, preoperative chemoradiation therapy was found to confer a significant improvement in 5-year DFS (64.7% vs. 53.4% for postoperative patients; P = .011).
    • Similar to the German Rectal Cancer Study, there was no significant difference in OS between treatment arms (74.5% for preoperative chemoradiation therapy vs. 65.6% for postoperative chemoradiation therapy; P =. 065).
Short-course preoperative radiation therapy

The use of short-course radiation therapy before surgery has been a standard approach in parts of Europe and Australia.

Evidence (short-course preoperative radiation therapy):

  1. The use of short-course radiation therapy was evaluated in a randomized study in the Swedish Rectal Cancer Trial (NCT00337545).[5][Level of evidence: 1iiA] In the trial, 1,168 patients younger than 80 years with stage I to stage III resectable rectal adenocarcinoma were randomly assigned to receive preoperative radiation therapy (25 Gy in five fractions) or to undergo immediate surgery. Patients did not receive adjuvant chemotherapy.
    • The 5-year OS rate was 58% in the radiation therapy group and 48% in the surgery group (P = .005).
    • The rate of local control was 11% in the radiation therapy group and 27% in the surgery group (P < .001).

    Subsequently, the Polish Rectal Trial and the Trans-Tasman Radiation Oncology Group (TROG) compared short-course preoperative radiation therapy with the standard long-course preoperative chemoradiation therapy administered with 5-FU.

  2. In the Polish Rectal Trial, 312 patients with clinical stage T3 or T4 rectal cancer were randomly assigned to receive preoperative radiation therapy (25 Gy in five fractions) followed by total mesorectal excision within 7 days, 6 months of adjuvant 5-FU/LV or preoperative chemoradiation therapy (50.4 Gy in 28 fractions with concurrent bolus 5-FU/LV), total mesorectal excision in 4 to 6 weeks after completion of radiation therapy, and 4 months of adjuvant 5-FU/LV.[6] The primary endpoint of the study was to detect a difference of at least 15% in sphincter preservation with a power of 80%.
    • The rates of sphincter preservation were 61.2% in the short-course group and 58% in the chemoradiation therapy group (P = .570).
    • The actuarial 4-year survival rate was 67.2% in the short-course group and 66.2% in the chemoradiation therapy group (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.69–1.48; P = .960).
    • The HR for local recurrence in the short-course group compared with the chemoradiation therapy group was 0.65 (95% CI, 0.32–1.28; P = .210).
    • There was no difference in late toxicity between the short-course group and the chemoradiation therapy group.
  3. In the TROG trial (TROG 01.04), 326 patients with ultrasound- or magnetic resonance imaging (MRI)–staged T3, N0 to N2, M0 rectal adenocarcinoma within 12 cm from the anal verge were randomly assigned to receive short-course radiation therapy (25 Gy in five fractions) followed by surgery 3 to 7 days later or long-course chemoradiation therapy (50.4 Gy in 28 fractions with concurrent continuous infusional 5-FU) followed by surgery in 4 to 6 weeks. All patients received adjuvant chemotherapy (5-FU/LV) after surgery. The trial was designed to have 80% power to detect a 10% difference in local recurrence at 3 years with a two-sided test at the 5% level of significance.[7]
    • Cumulative incidence of local recurrence at 3 years was 7.5% for the short-course group and 4.4% for the long-course group (P = .24).
    • OS at 5 years was 74% for the short-course group and 70% for the long-course group (HR, 1.12; 95% CI, 0.76–1.67; P = .62).
  4. The Medical Research Council of the United Kingdom and the National Cancer Institute of Canada built on the short-course experience and conducted a randomized study (MRC CR07 and NCIC-CTG C016) that compared short-course preoperative radiation therapy with selective postoperative chemoradiation therapy.[8] In the trial, 1,350 patients from 80 centers who had resectable rectal adenocarcinomas that were less than 15 cm from the anal verge were randomly assigned. Of note, pelvic MRI or ultrasound was not mandated. Patients randomly assigned to short-course radiation therapy received 25 Gy in five fractions followed by total mesorectal excision and then adjuvant chemotherapy according to the local center policy about nodal and margin status. Patients randomly assigned to selective postoperative chemoradiation therapy received immediate surgery followed by postoperative chemoradiation (45 Gy in 25 fractions with concurrent 5-FU) if their circumferential resection margin was 1 mm or smaller. Adjuvant chemotherapy for the group that received selective chemoradiation therapy was again given on the basis of local standards regarding nodal and margin status. [8]
    • The risk of local recurrence at 3 years was 4.4% in the preoperative short-course group and 10.6% in the selective chemoradiation therapy group (HR, 0.39; 95% CI, 0.27–0.58; P < .0001).
    • OS did not differ between the groups.

Taken together, these studies demonstrate that short-course preoperative radiation therapy and long-course preoperative chemoradiation therapy are both reasonable treatment strategies for patients with stage II or III rectal adenocarcinoma.

Postoperative chemoradiation therapy

Progress in the development of postoperative treatment regimens relates to the integration of systemic chemotherapy and radiation therapy, as well as redefining the techniques for both modalities. The efficacy of postoperative radiation therapy and 5-FU-based chemotherapy for stages II and III rectal cancer was established by a series of prospective, randomized clinical trials, including the following:[9-11][Level of evidence: 1iiA]

  • Gastrointestinal Tumor Study Group (GITSG-7175).
  • Mayo/North Central Cancer Treatment Group (NCCTG-794751).
  • National Surgical Adjuvant Breast and Bowel Project (NSABP-R-01).

These studies demonstrated an increase in DFS interval and OS when radiation therapy was combined with chemotherapy after surgical resection. After the publication in 1990 of the results of these trials, experts at a National Cancer Institute-sponsored Consensus Development Conference recommended postoperative combined-modality treatment for patients with stages II and III rectal carcinoma.[12] Since that time, preoperative chemoradiation therapy has become the standard of care, although postoperative chemoradiation therapy is still an acceptable alternative. (Refer to the Preoperative chemoradiation therapy section of this summary for more information.)

Additional evidence (postoperative chemoradiation therapy):

  1. Intergroup protocol 86-47-51 (MAYO-864751) compared continuous-infusion 5-FU (225 mg/m2/day throughout the entire course of radiation therapy) with bolus 5-FU (500 mg/m2/day for 3 consecutive days during the first and fifth weeks of radiation therapy).[13][Level of evidence: 1iiA]
    • A 10% improvement in OS was demonstrated with the use of continuous-infusion 5-FU.
  2. SWOG-9304 (NCT00002551), a three-arm randomized trial, determined whether continuous-infusion 5-FU given throughout the entire standard six-cycle course of adjuvant chemotherapy was more effective than continuous 5-FU given only during pelvic radiation therapy. Median follow-up was 5.7 years.[14]
    1. Arm 1 received bolus 5-FU in two 5-day cycles before (500 mg/m2/day) and after (450 mg/m2/day) radiation therapy, with protracted venous infusion 5-FU (225 mg/m2/day) during radiation therapy.
    2. Arm 2 received continuous infusion 5-FU before (300 mg/m2/day for 42 days), after (300 mg/m2/day for 56 days), and during (225 mg/m2/day) radiation therapy.
    3. Arm 3 received bolus 5-FU/LV in two 5-day cycles before (5-FU 425 mg/m2/day; LV 20 mg/m2/day) and after (5-FU 380 mg/m2/day; LV 20 mg/m2/day) radiation therapy, and bolus 5-FU/LV (5-FU 400 mg/m2/day; LV 20 mg/m2/day; days 1 to 4, every 28 days) during radiation therapy. Levamisole (150 mg/day) was administered in 3-day cycles every 14 days before and after radiation therapy.
      • No DFS, OS, or locoregional failure difference was detected (across all arms: 3-year DFS, 67% to 69%; 3-year OS, 81% to 83%; locoregional failure, 4.6% to 8%).
      • Lethal toxicity was less than 1%, with grades 3 to 4 hematologic toxicity in 55% of patients in arm 1 and in 49% of the patients in arm 3, versus in 4% of patients in the continuous-infusion arm.[14][Level of evidence: 1iiA]
  3. The final study results of Intergroup trial 0114 (INT-0114) showed no survival or local-control benefit with the addition of LV, levamisole, or both to 5-FU administered postoperatively for patients with stages II and III rectal cancers at a median follow-up of 7.4 years.[15][Level of evidence: 1iiA]
  4. A pooled analysis of 3,791 patients enrolled in clinical trials demonstrated that, for patients with T3, N0 disease, the 5-year OS rate with surgery plus chemotherapy (OS, 84%) compared favorably with the survival rates of patients treated with surgery plus radiation therapy and bolus chemotherapy (OS, 76%) or surgery plus radiation therapy and protracted-infusion chemotherapy (OS, 80%).[16]

Chemotherapy Regimens

Many academic oncologists suggest that LV/5-FU/oxaliplatin (FOLFOX) be considered the standard for adjuvant chemotherapy in rectal cancer. However, there are no data about rectal cancer to support this consideration. FOLFOX has become the standard arm in the latest Intergroup study evaluating adjuvant chemotherapy in rectal cancer. An Eastern Cooperative Oncology Group trial (ECOG-E5202 [NCT00217737]) randomly assigned patients with stage II or III rectal cancer who received preoperative or postoperative chemoradiation therapy to 6 months of FOLFOX with or without bevacizumab, but this trial closed because of poor accrual; no efficacy data are available.

Preoperative oxaliplatin with chemoradiation therapy

Oxaliplatin has also been shown to have radiosensitizing properties in preclinical models.[17] Phase II studies that combined oxaliplatin with fluoropyrimidine-based chemoradiation therapy have reported pathologic complete response rates ranging from 14% to 30%.[18-22] Data from multiple studies have demonstrated a correlation between rates of pathologic complete response and endpoints including distant metastasis-free survival, DFS, and OS.[23-25]

There is no current role for off-trial use of concurrent oxaliplatin and radiation therapy in the treatment of patients with rectal cancer.

Evidence (preoperative oxaliplatin with chemoradiation therapy):

  1. The ACCORD 12/0405-Prodige 2 trial, which randomly assigned 598 patients with clinically staged T2 or T3 or resectable T4 rectal cancer accessible by digital rectal examination to either preoperative radiation therapy (45 Gy in 25 fractions over 5 weeks) with capecitabine (800 mg/m2 twice daily 5 of every 7 days) or to a higher dose of radiation (50 Gy in 25 fractions over 5 weeks) with the same dose of capecitabine and oxaliplatin (50 mg/m2 weekly). Total mesorectal excision was performed in 98% of both groups at a median interval of 6 weeks after chemoradiation therapy was completed.[26]
    • Pathologic complete response was the primary endpoint (albeit never validated as a true surrogate of OS). A higher percentage of patients achieved a pathologic complete response in the oxaliplatin-treated group (19.2% vs. 13.9%); however, the difference did not reach statistical significance (P = .09).
    • The rate of grade 3 or 4 toxicity was significantly higher in the oxaliplatin-treated group (25% vs. 11%; P < .001), and there was no difference in the rate of sphincter-sparing surgery (75% vs. 78%).
  2. Similarly, the STAR-01 trial investigated the role of oxaliplatin combined with 5-FU chemoradiation for locally advanced rectal cancer.[27][Level of evidence: 1iiA] This Italian study randomly assigned 747 patients with resectable, locally advanced, clinically staged T3 or T4 and/or clinical N1 to N2 adenocarcinoma of the mid- to low-rectum to receive either continuous-infusion 5-FU with radiation therapy or to receive the same regimen in combination with oxaliplatin (60 mg/m2). Although the primary endpoint was OS, a protocol-planned analysis of response to preoperative therapy has been preliminarily reported.
    • The rate of pathologic complete response was equivalent at 16% in both arms (odds ratio, 0.98; 95% CI, 0.66–1.44; P = .904).
    • There was no difference noted in the rate of pathologically positive lymph nodes, tumor infiltration beyond the muscularis propria, or the rate of circumferential margin positivity.
    • An increase in grades 3 to 4 treatment-related acute toxicity was noted with the addition of oxaliplatin (24% vs. 8%; P <.001). Longer-term outcomes including OS have not yet been reported.
  3. The NSABP-R-04 trial randomly assigned 1,608 patients with clinically staged T3 or T4 or clinical node-positive adenocarcinoma within 12 cm of the anal verge in a 2 × 2 factorial design to one of the following four treatment groups:
    1. Intravenous continuous infusion 5-FU with radiation therapy.
    2. Capecitabine with radiation therapy.
    3. Intravenous continuous infusion 5-FU plus weekly oxaliplatin with radiation therapy.
    4. Capecitabine plus weekly oxaliplatin with radiation therapy.

    The primary objective of this study is locoregional disease control.[28][Level of evidence: 1iiD] Preliminary results, reported in abstract form at the 2011 American Society of Clinical Oncology annual meeting, demonstrated the following:

    • There was no significant difference in the rates of pathologic complete response, sphincter-sparing surgery, or surgical downstaging between the 5-FU and capecitabine regimens or between the regimens with and without oxaliplatin.
    • Patients treated with oxaliplatin had significantly higher rates of grade 3 and grade 4 acute toxicity (15.4% vs. 6.6%; P < .001).
  4. The German CAO/ARO/AIO-04 trial randomly assigned 1,236 patients with clinically staged T3 to T4 or clinical node-positive adenocarcinoma within 12 cm from the anal verge to receive either concurrent chemoradiation therapy with 5-FU (week 1 and week 5) or concurrent chemoradiation therapy with 5-FU daily (250 mg/m2) and oxaliplatin (50 mg/m2).[29][Level of evidence: 1iiD]
    • In contrast to the previous studies, a significantly higher rate of pathologic complete response was achieved in patients who received oxaliplatin (17% vs. 13%; P = .038).
    • There was no significant difference in rates of overall grades 3 and 4 toxicity; however, diarrhea and nausea and vomiting were more common among those treated with oxaliplatin.
    • The 5-FU schedules in this study differed between the two arms, which may have contributed to the difference in outcomes noted. Longer follow-up will be necessary to determine the effect on the primary endpoint of the study, DFS.

Postoperative oxaliplatin-containing regimens

On the basis of results of several studies, oxaliplatin as a radiation sensitizer does not appear to add any benefit in terms of primary tumor response, and it has been associated with increased acute treatment-related toxicity. The question of whether oxaliplatin should be added to adjuvant 5-FU/LV for postoperative management of stages II and III rectal cancer is an ongoing debate. There are no randomized phase III studies to support the use of oxaliplatin for the adjuvant treatment of rectal cancer. However, the addition of oxaliplatin to 5-FU/LV for the adjuvant treatment of colon cancer is now considered standard care.

Evidence (postoperative oxaliplatin):

  1. In the randomized Multicenter International Study of Oxaliplatin/5-Fluorouracil/LV in the Adjuvant Treatment of Colon Cancer (MOSAIC) study, the toxic effects and efficacy of FOLFOX4 (a 2-hour infusion of 200 mg/m2 LV, followed by a bolus of 400 mg/m2 5-FU, and then a 22-hour infusion of 600 mg/m2 5-FU on 2 consecutive days every 14 days for 12 cycles, plus a 2-hour infusion of 85 mg/m2 oxaliplatin on day 1, given simultaneously with LV) were compared with the same 5-FU/LV regimen without oxaliplatin when administered for 6 months. Each arm of the trial included 1,123 patients.[30]
    1. Preliminary results of the study, with 37 months of follow-up, demonstrated a significant improvement in DFS at 3 years in favor of FOLFOX4 (77.8% vs. 72.9%; P = .01). When initially reported, there was no difference in OS.[31][Level of evidence: 1iiDii]
    2. Further follow-up at 6 years demonstrated that the OS for all patients (both stage II and stage III) entered into the study was not significantly different (OS, 78.5% FOLFOX4 vs. 76.0% 5-FU/LV group; HR, 0.84; 95% CI, 0.71–1.00).
      • On subset analysis, the 6-year OS in patients with stage III colon cancer was 72.9% in the patients who received FOLFOX4 and 68.9% in the patients who received 5-FU/LV (HR, 0.80; 95% CI, 0.65–0.97; P = .023).[31][Level of evidence: 1iiA]
      • Patients treated with FOLFOX4 experienced more frequent toxic effects, consisting mainly of neutropenia (41% > grade 3) and reversible peripheral sensory neuropathy (12.4% > grade 3).
  2. The results of the now completed NSABP-C-07 (NCT00004931) study confirmed and extended the results of the MOSAIC trial.[32] In NSABP C-07, 2,492 patients with stage II or III colon or rectal cancer were randomly assigned to receive either FLOX (2-hour intravenous infusion of 85 mg/m2 oxaliplatin on days 1, 15, and 29 of each 8-week treatment cycle, followed by a 2-hour intravenous infusion of 500 mg/m2 LV plus bolus 500 mg/m2 5-FU 1 hour after the start of the LV infusion on days 1, 8, 15, 22, 29, and 36, followed by a 2-week rest period, for a total of three cycles [24 weeks]) or the same chemotherapy without oxaliplatin (Roswell Park regimen).
    • The 3- and 4-year DFS rates were 71.8% and 67% for the Roswell Park regimen and 76.1% and 73.2% for FLOX, respectively.
    • The HR was 0.80 (95% CI, 0.69–0.93), a 20% risk reduction in favor of FLOX (P < .004).

It is unclear whether the results these colon cancer trials can be applied to the management of patients with rectal cancer. There are no randomized phase III studies to support the routine practice of administering FOLFOX as adjuvant therapy to patients with rectal cancer.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II rectal cancer and stage III 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

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  2. Sauer R, Becker H, Hohenberger W, et al.: Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351 (17): 1731-40, 2004. [PUBMED Abstract]
  3. Sauer R, Liersch T, Merkel S, et al.: Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol 30 (16): 1926-33, 2012. [PUBMED Abstract]
  4. Roh MS, Colangelo LH, O'Connell MJ, et al.: Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol 27 (31): 5124-30, 2009. [PUBMED Abstract]
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  7. Ngan SY, Burmeister B, Fisher RJ, et al.: Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04. J Clin Oncol 30 (31): 3827-33, 2012. [PUBMED Abstract]
  8. Sebag-Montefiore D, Stephens RJ, Steele R, et al.: Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet 373 (9666): 811-20, 2009. [PUBMED Abstract]
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  10. Krook JE, Moertel CG, Gunderson LL, et al.: Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med 324 (11): 709-15, 1991. [PUBMED Abstract]
  11. Fisher B, Wolmark N, Rockette H, et al.: Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01. J Natl Cancer Inst 80 (1): 21-9, 1988. [PUBMED Abstract]
  12. NIH consensus conference. Adjuvant therapy for patients with colon and rectal cancer. JAMA 264 (11): 1444-50, 1990. [PUBMED Abstract]
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  14. Smalley SR, Benedetti JK, Williamson SK, et al.: Phase III trial of fluorouracil-based chemotherapy regimens plus radiotherapy in postoperative adjuvant rectal cancer: GI INT 0144. J Clin Oncol 24 (22): 3542-7, 2006. [PUBMED Abstract]
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  19. Machiels JP, Duck L, Honhon B, et al.: Phase II study of preoperative oxaliplatin, capecitabine and external beam radiotherapy in patients with rectal cancer: the RadiOxCape study. Ann Oncol 16 (12): 1898-905, 2005. [PUBMED Abstract]
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  26. Gérard JP, Azria D, Gourgou-Bourgade S, et al.: Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2. J Clin Oncol 28 (10): 1638-44, 2010. [PUBMED Abstract]
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  28. Roh MS, Yothers GA, O'Connell MJ, et al.: The impact of capecitabine and oxaliplatin in the preoperative multimodality treatment in patients with carcinoma of the rectum: NSABP R-04. [Abstract] J Clin Oncol 29 (Suppl 15): A-3503, 2011.
  29. Rödel C, Liersch T, Becker H, et al.: Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol 13 (7): 679-87, 2012. [PUBMED Abstract]
  30. André T, Boni C, Mounedji-Boudiaf L, et al.: Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 350 (23): 2343-51, 2004. [PUBMED Abstract]
  31. André T, Boni C, Navarro M, et al.: Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol 27 (19): 3109-16, 2009. [PUBMED Abstract]
  32. de Gramont A, Boni C, Navarro M, et al.: Oxaliplatin/5FU/LV in the adjuvant treatment of stage II and stage III colon cancer: efficacy results with a median follow-up of 4 years. [Abstract] J Clin Oncol 23 (Suppl 16): A-3501, 246s, 2005.
  • Updated: December 16, 2014