The aim of this systematic review was to determine the optimal duration of chemotherapy. Currently, the standard of duration is based upon studies performed in the 90's, and focus on the determination of the best schedule of 5FU treatment alone or in combination with folinic acid or levamisole and the optimal duration of the adjuvant treatment. Different durations of 5FU based treatment were compared: 6 months versus 9-12 months. Shorter duration of chemotherapy (3-6 months) compared with longer duration (9-12 months) did not result in poorer relapse free survival or overall survival. Consequently, the duration of 5FU based chemotherapy in adjuvant setting for colorectal cancer can be reduced to 6 months.
A recently published study compared 3 months continuous infusion of 5FU to 6 months bolus 5FU, and showed the benefit of this 3 months schedule. Therefore, future studies will evaluate the efficacy of shorter chemotherapy with the new gold-standard: FOLFOX (combining oxaliplatine and 2 days continuous 5FU, bimonthly) in order to minimize the neurotoxicity of oxaliplatine.
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.
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.
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.
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.
Patients with surgically resected colorectal cancer with high risk of recurrence.
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.
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).