Adjuvant chemoradiotherapy of advanced resectable rectal cancer: results of a randomised trial comparing modulation of 5-fluorouracil with folinic acid or with interferon-α

Abstract

Background:Standard adjuvant chemoradiotherapy of rectal cancer still consists of 5-fluorouracil (5-FU) only. Its cytotoxicity is enhanced by folinic acid (FA) and interferon-α (INFα). In this trial, the effects of FA and IFNα on adjuvant 5-FU chemoradiotherapy in locally advanced rectal cancer were investigated.Methods:Patients with R0-resected rectal cancer (UICC stage II and III) were stratified and randomised to a 12-month adjuvant chemoradiotherapy with 5-FU, 5-FU+FA, or 5-FU+IFNα. All patients received levamisol and local irradiation with 50.4 Gy.Results:Median follow-up was 4.9 years (n=796). Toxicities (WHO III+IV) were observed in 32, 28, and 58% of patients receiving 5-FU, 5-FU+FA, and 5-FU+IFNα, respectively. No differences between the groups were observed for local or distant recurrence. Five-year overall survival (OS) rates were 60.3% (95% confidence interval (CI): 54.3–65.8), 60.4% (54.4–65.8), and 59.9% (53.0–66.1) for 5-FU, 5-FU+FA, and 5-FU+IFNα, respectively. A subgroup analysis in stage II (pT3/4pN0) disease (n=271) revealed that the addition of FA tended to reduce the 5-year local recurrence (LR) rate by 55% and increase recurrence-free survival and OS rates by 12 and 13%, respectively, relative to 5-FU alone.Conclusions:Interferon-α cannot be recommended for adjuvant chemoradiotherapy of rectal cancer. In UICC stage II disease, the addition of FA tended to lower LR and increased survival. The addition of FA to 5-FU may be an effective option for adjuvant chemoradiotherapy of UICC stage II rectal cancer.

A systematic review of outcome reporting in colorectal cancer surgery

“…The most frequently recorded mortality outcome was ‘overall survival’, which was measured in 60 (30.9%) studies. However, ‘overall survival’ was defined in only 20 studies with six different definitions . ‘Disease‐free survival’ was reported in 43 (22.2%) articles and defined in 27 with 16 unique definitions .…”

“…A further 13 (19.7%) individual outcomes concerned the time to recurrence, six (9.1%) concerned disease progression and two (3.0%) reported second primary malignancies. The two most frequently reported cancer‐related individual outcomes were ‘local recurrence’ (recorded in 44 studies and defined in 19, in 15 different ways) and ‘distant recurrence’ (recorded in 23 studies and defined in four, in four different ways) .…”

“…A further 13 (19.7%) individual outcomes concerned the time to recurrence, six (9.1%) concerned disease progression and two (3.0%) reported second primary malignancies. The two most frequently reported cancer-related individual outcomes were 'local recurrence' (recorded in 44 studies and defined in 19, in 15 different ways) [12,13,17,22,27,33,38,[58][59][60][61][62][63][64][65][66][67][68][69] Intial search results n = 5644…”

“…The most frequently recorded mortality outcome was 'overall survival', which was measured in 60 (30.9%) studies. However, 'overall survival' was defined in only 20 studies with six different definitions[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. 'Disease-free survival' was reported in 43 (22.2%) articles and defined in 27 with 16 unique definitions[13][14][15][17][18][19][20][21][22][23]26,28,[30][31][32][33][34][35][36][37][38][39][40][41][42][43][44].…”

Sphincter-preserving surgery after preoperative radiochemotherapy for T3 low rectal cancers

“…Postoperative radiochemotherapy followed. The conventional treatments were established for local control and disease-free interval following surgical resection (15,16), but improving sphincter preservation constituted a challenge. Colostomy caused serious inconvenience to the patients and limited their quality of life.…”