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Meta-Analysis
. 2010 Jan 20;2010(1):CD007046.
doi: 10.1002/14651858.CD007046.pub2.

Duration of adjuvant chemotherapy for patients with non-metastatic colorectal cancer

Gaëtan Des Guetz  1 , Bernard Uzzan, Jean-Francois Morere, Gerard Perret, Patrick Nicolas
Affiliations
Meta-Analysis

Duration of adjuvant chemotherapy for patients with non-metastatic colorectal cancer

Gaëtan Des Guetz et al. Cochrane Database Syst Rev. .

Abstract

Background: Surgery of primary tumour is the backbone of colorectal cancer treatment (CRC). But in stage III cancer, metastatic or local relapse is often observed (50%). So, adjuvant treatment is always considered in this setting. The best treatment duration of hypothetic disease is not easy to define. Adjuvant chemotherapy for CRC actually lasts 6 months. The choice of optimal duration is based upon old studies using 5-fluorouracil (5FU). During the last ten years, results of major randomized controlled studies (RCTs) comparing different durations of treatments and different schedules in adjuvant setting were published. Several studies compared a 6-month chemotherapy with a longer treatment. Conversely, a single study by Chau et al compared a 6 month chemotherapy with continuous treatment lasting 3 months. But the optimal duration of these chemotherapies could be challenged. Even though the optimal duration of chemotherapy in CRC is a major issue, it has never been answered adequately.

Objectives: To evaluate the optimal duration of adjuvant treatment, we performed a meta-analysis of all RCTs comparing two durations of adjuvant treatment, 6 months versus 9 to 12 months.

Search strategy: Publications were identified from PubMed (February 28th, 2009), Embase, and the Cochrane Database of Clinical Controlled Trials (CENTRAL) in the Cochrane Library 2009 issue 1. Reviews and books were also scrutinized. Abstracts were reviewed from ASCO annual meetings proceedings from 1998 to 2009.

Selection criteria: Patients with surgically resected colorectal cancer with high risk of recurrence.

Data collection and analysis: Several RCTs compared shorter versus longer durations of chemotherapy, 6 studies for overall survival (OS) and 7 studies for relapse free survival (RFS), for a total of 10326 patients, mean age 63.1 years, including 9826 colon and 500 rectum cancers.

Main results: Treatments were always based on 5-FU. Two studies were excluded, an epidemiological study and a study comparing continuous treatment during 3 months with conventional chemotherapy during 6 months. The later because it compared 2 durations less than or equal to 6 months. Shorter duration of chemotherapy (3-6 months) compared with longer duration (9-12 months) was not associated to poorer RFS (RR =0.96, 95% CI : 0.90-1.02) and OS (RR = 0.96 ; 95% CI : 0.91-1.02).

Authors' conclusions: The present meta-analysis confirmed that adjuvant chemotherapy of CRC should not last for more than 6 months. Prolonged duration would result in lower benefit to risk ratio. However, the results do not make it possible to favour either 3 or 6 month durations. They should help design a future RCT comparing different durations of continuous treatment.

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Conflict of interest statement

None known

Figures

1
1
Forest plot of comparison: 2 Overall survival (OS), outcome: 2.1 Overall survival.
2
2
Forest plot of comparison: 1 Relapse free survival (RFS), outcome: 1.1 Relapse free survival.
1.1
1.1. Analysis
Comparison 1 Overall survival (OS), Outcome 1 Overall survival.
2.1
2.1. Analysis
Comparison 2 Relapse free survival (RFS), Outcome 1 Relapse free survival.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD007046

References

References to studies included in this review

Andre 2007 {published data only}
    1. André T. Phase III Study Comparing a Semimonthly With a Monthly Regimen of Fluorouracil and Leucovorin As Adjuvant Treatment for Stage II and III Colon Cancer Patients: Final Results of GERCOR C96.1. J Clin Oncol 2007;25(24):3732‐8. - PubMed
Haller 2005 {published data only}
    1. Haller DG, Catalano PJ, Macdonald JS, O'Rourke MA, Frontiera MS, Jackson DV, Mayer RJ. Phase III study of fluorouracil, leucovorin, and levamisole in high‐risk stage II and III colon cancer: final report of Intergroup 0089. J Clin Oncol 2005;23(34):8671‐8678. - PubMed
Ito 2000 {published data only}
    1. Ito K, Kato T, Koike A, Miura K, Yamaguchi A, Sakou T, Takagi H. Optimum duration of oral adjuvant chemotherapy of HCFU for colorectal cancer; review of 5‐year follow‐up.. Anticancer Res 2000;20(6C):4681‐6. - PubMed
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References to studies excluded from this review

Chau 2005 {published data only}
    1. Chau I, Norman AR, Cunningham D, Tait D, Ross PJ, Iveson T, Hill M, Hickish T, Lofts F, Jodrell D, Webb A, Oates JR. A randomised comparison between 6 months of bolus fluorouracil/leucovorin and 12 weeks of protracted venous infusion fluorouracil as adjuvant treatment in colorectal cancer.. Ann Oncol 2005;16(4):549‐557. - PubMed
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