Quantitative analysis of orthotopic human (HT29) primary colonic adenocarcinomas showed that doublet LDM cyclophosphamide + MTD capecitabine increased median nuclear HIF‐1α protein levels by 12‐fold compared to vehicle‐treated controls (P = 3.9 × 10−3; Fig 1A and Appendix Fig S1A); by contrast, switching to a doublet LDM cyclophosphamide+capecitabine regimen blocked ≈97% of HIF‐1α induction (P = 2 × 10−3; Fig 1A and Appendix Fig S1A). Here, HIF1A is linked to colon adenocarcinoma.