cytarabine

Overview

Cytarabine (cytosine arabinoside, ara-C) is a pyrimidine nucleoside analog that inhibits DNA polymerase and is incorporated into DNA, causing chain termination. It is a cornerstone of acute myeloid leukemia (AML) induction and consolidation chemotherapy, typically combined with an anthracycline. Standard induction regimen is “7+3” (7 days cytarabine continuous infusion + 3 days anthracycline), or variants such as ICE (idarubicin + cytarabine + etoposide).

Evidence in the corpus

  • Used as part of ICE induction chemotherapy (idarubicin+cytarabine+etoposide) across three AMLSG intensive-therapy trials (AML-HD98A, AMLSG-07-04, AML-HD98B) in 1540 adults with AML; treatment backbone for genomic subgrouping and prognostic study defining 11 mutually exclusive AML classes PMID:27276561
  • Conventional anthracycline + cytarabine induction in TP53-mutant AML yields median survival of only 4–6 months and CR rates of 20–30%; the WashU prospective trial (n=116) contrasted this against decitabine which achieved 100% blast clearance in TP53-mutant AML with a 12.7-month median OS PMID:27959731
  • Dose-reduced cytarabine (with gemtuzumab) used in a personalized chemotherapy regimen for a pediatric patient (LPP_10) carrying a germline TP53 LP/PV (Li-Fraumeni syndrome) who developed BCP-ALL → AML; the patient achieved remission following haploidentical HSCT from the maternal grandmother after stem-cell rejection PMID:29489754

Resistance mechanisms

Cancer types (linked)

Sources

  • PMID:27276561
  • PMID:27959731 — Welch et al. 2016, NEJM. WashU 10-day decitabine AML/MDS trial (N=116); cytarabine + anthracycline induction as comparator; TP53-mutant AML has CR rate 20–30% and median OS 4–6 months on cytarabine-based induction.
  • PMID:29489754 — Briese et al. 2018. Germline LP/PVs in 25 HBOC genes across 372 pediatric cancer patients; dose-reduced cytarabine used in personalized regimen for LFS patient (TP53 LP/PV) with BCP-ALL → AML.

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