Table 1

Published studies discussing gastrointestinal toxicities in early-onset colorectal cancer (EO-CRC) patients retrieved through our systematic review process.

Authors, ref.CountryStudy setting/study typeTotal n of participants
(cases; controls)
EO-CRC age cut-off (years of age)Gender
F/M (%)
Control cohortTreatment providedMain results
Raimondi et al, 202210ItalyAdv./post hoc analysis of Valentino trial229
(35;194)
<5034/66YesFOLFOX plus panitumumab first-line treatment
  • EO-CRC experienced higher rate of any grade nausea (43% vs 32%, p=0.249) and vomiting (26% vs 16%, p=0.226).

Meng et al, 202211USAAdv./post hoc analysis of 3 clinical trials (NCT00272051; NCT 00305188; NCT00364013)1223
(179;1044)
<50, 50–65, >6540/60YesFOLFOX
  • EO-CRC (<50 yo vs 50–65 years vs >65 years) had higher incidence of nausea and vomiting (69.3% vs 57.6% vs 60.4%, p=0.019).

  • Lower incidence of severe diarrhoea in EO-CRC pts (6.1% vs 9.1% vs 13.0%, p=0.02).

Antoniotti et al, 20229ItalyAdv./post hoc analysis of TRIBE and TRIBE2 studies1187
(194; 993)
< 5042/58YesFOLFOXIRI+bevacizumab or doublets+bevacizumab
  • EO-CRC had lower risk of diarrhoea (9% vs 14%, p=0.04) and higher of nausea and vomiting (69% vs 57%, p<0.01; 44% vs 32%, p<0.01).

  • Among pts receiving FOLFOXIRI/bevacizumab, the incidence of G3-G4 GI adverse events (mucositis, nausea, diarrhoea) was not significantly different in EO-CRC.

Fontana et al, 20213InternationalAdj./post hoc analysis of the IDEA cohort16 349
(1564; 14785)
< 5043.6/56.4YesCAPOX or FOLFOX (3 or 6 months)
  • Higher incidence of nausea/vomiting (58,2% vs 44,8% p<0.0001; 22,3% vs 16.1% p<0.0001) but not diarrhoea (42.1% vs 39.4% p=0.3765) in pts with EO-CRC.

Perl et al, 20168IsraelAdj. and Adv./retrospective cohort50 pts with GI malignancies (80% were CRC pts) (40; 0)< 4052/48NoSurgery, chemotherapy, radiotherapy, combined modality
  • Diarrhoea and abdominal pain significantly increased during-treatment administration (p<0.05) in EO-CRC pts.

Suzuki et al, 20167JapanN.S./retrospective179
(22; 157)
< 5039/61YesFOLFOX, XELOX, FOLFIRI
  • Female (OR 2.870, 95% CI 1.139 to 7.228; p=0.025)* and age <50 (OR 4.277; 95% CI 1.472 to 12.424; p=0.008) were risk factors for CINV.

Sanford et al, 20146USAAdj and Adv./multicentric prospective study1544 breast cancer and 718 CRC (37; 681)< 4048/52YesN.S.
  • EO-CRC pts had more nausea (adjusted OR 2.59, 95% CI 1.02 to 6.59 p<0.05), while G3-G4 diarrhoea, vomiting or mucositis were not significantly different.

Hubbard et al, 20125InternationalAdj./post hoc analysis of 10 randomised phase III trials33 574 (5,817†; 27 757)< 40 and < 50‡45/55YesFluorouracil-based monotherapy and combination chemotherapy
  • EO-CRC <40: more nausea and vomiting (10% vs 7%, OR 0.64 p 0.04), but no difference in diarrhoea (15% vs 16%, p>0.05).

Blanke et al, 20114InternationalAdv./post hoc analysis of 9 phase III trials6284
(793; 5491)
< 5036.5/63.5YesFluorouracil-based monotherapy and combination chemotherapy
  • More G3 nausea (10% vs 7%; p=0.01); rarer severe diarrhoea (11% vs 14%; p=0.001) in patients with EO-CRC.

  • *Reported as a potential factor influencing a higher gastrointestinal symptoms incidence in EO-CRC cohort.

  • †Number of patients included in the younger than 50 years of age cohort.

  • ‡Two cohorts of patients with EO-CRC were studied. Nausea grading is reported according to Common Terminology Criteria for Adverse Events (CTCAE).

  • Adj, Adjuvant setting; Adv, Advanced/metastatic setting; CINV, chemotherapy-induced nausea or vomiting; F, female; G, grade; GI, gastrointestinal; LO-CRC, later-onset colorectal cancer; M, male; n, number; Neoadj, neoadjuvant; N.S., not specified; Prosp, prospective; Pts, patients; ref, reference; Retro, retrospective.