Evidence map›Paper›PMID 21915801›Full record

Trial reportCancer immunology, immunotherapy : CII2012

Metronomic cyclophosphamide treatment in metastasized breast cancer patients: immunological effects and clinical outcome.

Yingzi Ge, Christoph Domschke, Natalija Stoiber, Sarah Schott, Joerg Heil, Joachim Rom, Maria Blumenstein, Janina Thum, Christof Sohn, Andreas Schneeweiss and 2 more

Registry-linked trialOpen access · greenAbstract readClinical Trial
In one paragraph

Trial report in Cancer immunology, immunotherapy : CII, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04895761 (Phase Ib Study of Neoadjuvant DPX-Survivac, Aromatase Inhibition, and With/Without Radiotherapy or Cyclophosphamide in HR+HER2- Breast Cancer), which is not on this map. Cited by 122 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
122citing papers in PubMed, 1 pooled it
5.4field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04895761 phase1active not recruitingnot on this mapstarted 2021, after this paper: background citation

Phase Ib Study of Neoadjuvant DPX-Survivac, Aromatase Inhibition, and With/Without Radiotherapy or Cyclophosphamide in HR+HER2- Breast Cancer

TypeinterventionalSponsorProvidence Health & ServicesRan2021 to 2026Enrolled6ConditionsBreast CancerArmsDPX-Survivac, Letrozole 2.5mg, Cyclophosphamide 50mg, XRT 10Gy x2
3 · Its place in the literature

Who cites it

122 citing papers in PubMed, 1 synthesis or guideline pooled it, 225 citations in OpenAlex.

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  5. Low-Dose Cyclophosphamide Induces Antitumor T-Cell Responses, which Associate with Survival in Metastatic Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017
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62 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 2 countries.

Yingzi GeDivision of Translational Immunology, Tumor Immunology Program, German Cancer Research Center (DKFZ), National Center for Tumor Diseases (NCT), INF 460, 69120, Heidelberg, Germany.
Christoph Domschke
Natalija Stoiber
Sarah Schott
Joerg Heil
Joachim Rom
Maria Blumenstein
Janina Thum
Christof Sohn
Andreas Schneeweiss
Philipp Beckhove
Florian Schuetz
University Hospital Heidelberg · DEHeidelberg University · DENational Center for Tumor Diseases · DEGerman Cancer Research Center · DEKantonsspital Baden · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Severe immune suppression is frequent in late-stage tumor patients and promotes tumor immune evasion and subsequent tumor progression. Regulatory T cells (Treg) are major suppressors of anti-tumor immune responses. Therefore, targeting of Treg has become a key goal of anti-tumor therapy. Several preclinical and clinical observations suggest that Treg can be depleted by cyclophosphamide. Over a period of 3 months, we investigated the effect of metronomic low-dose cyclophosphamide on Treg numbers, suppressive capacity and proliferation on endogenous anti-tumor T-cell responses and on their correlation to clinical outcome in 12 patients with treatment-refractory metastasized breast cancer who received single-agent 50 mg cyclophosphamide p.o. daily. Cyclophosphamide treatment initially caused a significant reduction in circulating Treg by more than 40% (P = 0.002). However, Treg numbers completely recovered during the treatment due to increased proliferative activity and maintained their suppressive capacity. Treg depletion coincided with a strong increase in breast tumor-reactive T cells (P = 0.03) that remained at high levels during the whole period. Numbers of tumor-reactive T cells but not of Treg correlated with disease stabilization (P = 0.03) and overall survival (P = 0.027). We conclude that metronomic low-dose cyclophosphamide only transiently reduces Treg but induces stable tumor-specific T-cell responses, which correlate with improved clinical outcome in advanced-stage breast cancer patients.

Indexed as

AdultAgedAntineoplastic Agents, AlkylatingBreast NeoplasmsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell Line, TumorCyclophosphamideDose-Response Relationship, DrugFemaleHumansInterferon-gammaLymphocyte CountMiddle AgedNeoplasm MetastasisSurvival AnalysisAntineoplastic Agents, AlkylatingCyclophosphamideInterferon-gamma

Identifiers

PMID21915801
PMCPMC11028651
OpenAlexW2078448383

What OpenQuestion holds

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Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.