Evidence map›Paper›PMID 25564570›Full record

Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2015

Tadalafil augments tumor specific immunity in patients with head and neck squamous cell carcinoma.

Joseph A Califano, Zubair Khan, Kimberly A Noonan, Lakshmi Rudraraju, Zhe Zhang, Hao Wang, Steven Goodman, Christine G Gourin, Patrick K Ha, Carole Fakhry and 12 more

Erratum issued Registry-linked trialAbstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT00894413 (A Phase II Trial of Tadalafil in Patients With Squamous Cell Carcinoma of the Upper Aero Digestive Tract), which is not on this map. Cited by 131 papers.

0numbers the graph read from it
0cells of the map it votes in
131citing papers in PubMed
–field-weighted citation impact
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.

NCT00894413 phase2completednot on this map

A Phase II Trial of Tadalafil in Patients With Squamous Cell Carcinoma of the Upper Aero Digestive Tract

TypeinterventionalSponsorSidney Kimmel Comprehensive Cancer Center at Johns HopkinsRan2007 to 2012Enrolled45ConditionsHead and Neck Squamous Cell CarcinomaArmsTadalafil, Placebo Pill
3 · Its place in the literature

Who cites it

131 citing papers in PubMed.

  1. Trial
  2. Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 Peptide Vaccine for Prevention of Recurrent Colorectal Adenoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023
    Trial
  3. Tadalafil Enhances Immune Signatures in Response to Neoadjuvant Nivolumab in Resectable Head and Neck Squamous Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Trial
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. MDSC: a new potential breakthrough in CAR-T therapy for solid tumors.Cell communication and signaling : CCS · 2024
    Review
  17. Review
  18. Article
  19. Translational Frontiers and Clinical Opportunities of Immunologically Fitted Radiotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Review
  20. Targeting neutrophils: Mechanism and advances in cancer therapy.Clinical and translational medicine · 2024
    Review

71 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors.

Joseph A CalifanoDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland. Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland. Milton J Dance Head and Neck Center, Greater Baltimore Medical Center, Baltimore, Maryland. jcalifa@jhmi.edu iborrell@jhmi.edu.
Zubair KhanDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Kimberly A NoonanDepartment of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Lakshmi RudrarajuDepartment of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Zhe ZhangDivision of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Hao WangDivision of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Steven GoodmanDivision of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Christine G GourinDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Patrick K HaDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland. Milton J Dance Head and Neck Center, Greater Baltimore Medical Center, Baltimore, Maryland.
Carole FakhryDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland. Milton J Dance Head and Neck Center, Greater Baltimore Medical Center, Baltimore, Maryland.
John SaundersMilton J Dance Head and Neck Center, Greater Baltimore Medical Center, Baltimore, Maryland.
Marshall LevineDepartment of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland. Oncology Department, Greater Baltimore Medical Center, Baltimore, Maryland.
Mei TangOncology Department, Greater Baltimore Medical Center, Baltimore, Maryland.
Geoffrey NeunerOncology Department, Greater Baltimore Medical Center, Baltimore, Maryland.
Jeremy D RichmonDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Ray BlancoMilton J Dance Head and Neck Center, Greater Baltimore Medical Center, Baltimore, Maryland.
Nishant AgrawalDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Wayne M KochDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Shanthi MarurDepartment of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Donald T WeedDepartment of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida.
Paolo SerafiniDepartment of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida.
Ivan BorrelloDepartment of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland. jcalifa@jhmi.edu iborrell@jhmi.edu.

Funding

TUMOR SUPPRESOR GENE PROMOTER HYPERMETHYLATION FOR DETECTION OF HEAD AND NECKP50DE019032 · NIDCR · JOHNS HOPKINS UNIVERSITY · PI BEDI, ATUL · 2007 to 2016
$27.1M
Tumor Suppressor Gene Promoter Hypermethylation for Detection of Head/Neck CancerP50CA096784 · NCI · JOHNS HOPKINS UNIVERSITY · PI SIDRANSKY, DAVID · 2002 to 2006
$11.3M
Tadalafil Induced Modulation of Immune Response in HNSCCR21CA135635 · NCI · JOHNS HOPKINS UNIVERSITY · PI CALIFANO, JOSEPH A · 2009 to 2010
$722k
NCI NIH HHS 1R21CA135635NCI NIH HHS P50 CA096784NCI NIH HHS P50 CA19032NCI NIH HHS R21 CA135635NIDCR NIH HHS P50 DE019032
6 · The paper itself

Abstract

purposeTo determine if phosphodiesterase 5 (PDE5) inhibitors can augment immune function in patients with head and neck cancer through inhibition of myeloid-derived suppressor cells (MDSC). EXPERIMENTAL

designWe performed a randomized, prospective, double blinded, placebo controlled, phase II clinical trial to determine the in vivo effects of systemic PDE5 inhibition on immune function in patients with head and neck squamous cell carcinoma (HNSCC).

resultsTadalafil augmented immune response, increasing ex vivo T-cell expansion to a mean 2.4-fold increase compared with 1.1-fold in control patients (P = 0.01), reducing peripheral MDSC numbers to mean 0.81-fold change compared with a 1.26-fold change in control patients (P = 0.001), and increasing general immunity as measured by delayed type hypersensitivity response (P = 0.002). Tumor-specific immunity in response to HNSCC tumor lysate was augmented in tadalafil-treated patients (P = 0.04).

conclusionsThese findings demonstrate that tadalafil augments general and tumor-specific immunity in patients with HNSCC and has therapeutic potential in HNSCC. Evasion of immune surveillance and suppression of systemic and tumor-specific immunity is a significant feature of head and neck cancer development. This study demonstrates that a PDE5 inhibitor, tadalafil, can reverse tumor-specific immune suppression in patients with head and neck cancer, with potential for therapeutic application.

Indexed as

AdultAgedAged, 80 and overCarbolinesCarcinoma, Squamous CellCyclic Nucleotide Phosphodiesterases, Type 5FemaleHead and Neck NeoplasmsHumansImmunity, CellularMaleMiddle AgedPhosphodiesterase 5 InhibitorsSquamous Cell Carcinoma of Head and NeckTadalafilT-LymphocytesCarbolinesCyclic Nucleotide Phosphodiesterases, Type 5Phosphodiesterase 5 InhibitorsTadalafil

Identifiers

PMID25564570
PMCPMC4329916

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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.