irinotecan

Overview

Camptothecin-derivative topoisomerase I inhibitor; component of FOLFIRI/FOLFIRINOX and pediatric sarcoma regimens.

Evidence in the corpus

  • Listed among colorectal-style first-line regimens offered in appendiceal adenocarcinoma; GNAS-mut predominant MAAP tumors showed only 6% first-line response to such regimens vs 50% in RAS-mut predominant MAAP (P=.03) PMID:36493333.
  • Used in relapsed/high-risk regimens for extremity rhabdomyosarcoma in the MSKCC 2000–2021 cohort PMID:37315267.
  • KRASG12R-mutant PAAD patients were enriched among those receiving neoadjuvant FOLFIRINOX (fluorouracil + irinotecan + oxaliplatin + leucovorin) followed by resection (32.7% vs 17.9% for KRASG12D, p=0.094), suggesting possible KRAS-allele-specific chemosensitivity to irinotecan-containing regimens PMID:39214094.
  • Irinotecan + temozolomide was one of five PDTO-matched treatment regimens applied in sarcoma patients; normalized organoid viability correlated with time-to-next-treatment across the n=5 matched-treatment cohort (R²=0.921, p=0.009) PMID:39305899.
  • FOLFIRINOX (incorporating irinotecan) was administered to 38% of the curated 1,480-patient MSK PDAC cohort as first-line therapy; backbone choice between FOLFIRINOX and gemcitabine/nab-paclitaxel was not significantly associated with OS in 304 metastatic patients PMID:39753968.
  • Included in the CCLE pharmacogenomic screen across 947 cancer cell lines; sensitivity correlated with genomic features via elastic-net regression PMID:22460905
  • High TOP2A expression and amplification in metastatic PanNET patient PN4 (MSH6/MLH1-deficient, TMB ~11 mut/Mb) supported irinotecan recommendation in the POG NEN WGTA cohort PMID:24326773
  • In SCLC chemoresistant PDX models, EPZ011989 (EZH2 inhibitor) + irinotecan over 6 weekly cycles produced potent combinatorial activity; SLFN11-high chemonaive models achieved complete responses in 5/5 animals with EPZ + irinotecan; a single in vivo irinotecan dose induced EZH2 protein and H3K27me3 increases PMID:28196596.
  • Irinotecan-containing regimens (FOLFIRI) were used as chemotherapy in the 295-patient metastatic EGC cohort (MSK-IMPACT); MSI-H patients showed inferior PFS on cytotoxic regimens (4.8 vs 6.9 months) and are candidates for early immunotherapy instead PMID:29122777

Resistance mechanisms

  • GNAS-mut predominant appendiceal adenocarcinoma is associated with resistance to irinotecan-containing chemotherapy PMID:36493333.

Cancer types (linked)

  • APAD, RMS, ARMS
  • PAAD — pancreatic adenocarcinoma (FOLFIRINOX component)

Sources

This page was processed by crosslinker on 2026-05-09. - PMID:22460905

This page was processed by crosslinker on 2026-05-09. - PMID:24326773

This page was processed by crosslinker on 2026-05-09. - PMID:28196596

This page was processed by wiki-cli on 2026-05-14. - PMID:29122777

This page was processed by wiki-cli on 2026-05-15.