cyclophosphamide

Overview

Nitrogen mustard alkylating chemotherapy; backbone of CHOP-based lymphoma regimens and pediatric sarcoma protocols.

Evidence in the corpus

  • Component of curative-intent CHOP/CHOEP/EPOCH/BV-CH(E)P regimens used in 132 nodal PTCL patients at MSK; TP53 mutation (HR 3.1, P=.005) identified patients with inferior PFS on cyclophosphamide-containing induction PMID:37078708.
  • Used in extremity rhabdomyosarcoma chemotherapy backbones across COG/institutional protocols spanning 2000–2021 PMID:37315267.
  • Cyclophosphamide appears in the UCLA sarcoma PDTO drug library (sarcoma_ucla_2024) and is listed among NCCN-recommended regimens for rhabdomyosarcoma identified in the functional screen (alongside doxorubicin and vinorelbine). PMID:39305899
  • Component of the FC/FCR chemoimmunotherapy regimens evaluated in the CLL8 trial (n=538 CLL patients); mutated TP53, SF3B1, and novel driver RPS15 each predicted shorter PFS, and presence of any subclonal driver predicted shorter PFS (HR 1.6) in both FC and FCR arms PMID:26466571.
  • Referenced as a component of high-dose conditioning regimens for allogeneic SCT — the treatment modality with the largest survival benefit in the WashU AML/MDS decitabine trial (N=116); allogeneic SCT vs no SCT was the dominant Cox survival predictor (P<0.001) independent of TP53 status PMID:27959731

Resistance mechanisms

  • TP53 mutations and 17p deletions associate with markedly inferior PFS on CHOP-based induction in PTCL PMID:37078708.

Cancer types (linked)

Sources

  • PMID:37078708
  • PMID:37315267
  • PMID:39305899 — Al Shihabi et al. (Cell Stem Cell 2024). UCLA sarcoma PDTO biobank; cyclophosphamide as NCCN-listed RMS regimen component in functional screen.
  • PMID:26466571 — Landau et al. (Nature 2015). CLL8 trial genomics; FC/FCR regimen prognostic landscape in 538 CLL patients.
  • PMID:27959731 — Welch et al. 2016, NEJM. WashU AML/MDS decitabine trial; cyclophosphamide referenced as component of allogeneic SCT conditioning; SCT was the dominant survival predictor.

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