Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 May 20;10(3):00654-2023.
doi: 10.1183/23120541.00654-2023. eCollection 2024 May.

Characteristics and outcomes of gemcitabine-associated pulmonary hypertension

Pierre Mouillot  1   2 , Nicolas Favrolt  1   2 , Charles Khouri  3   4   5 , Aurélie Grandvuillemin  6 , Marie-Camille Chaumais  7   8   9 , Déborah Schenesse  1   2 , Andrei Seferian  9   10   11 , Xavier Jais  9   10   11 , Laurent Savale  9   10   11 , Guillaume Beltramo  1   2 , Olivier Sitbon  9   10   11 , Jean-Luc Cracowski  3   5 , Marc Humbert  9   10   11 , Marjolaine Georges  1   2 , Philippe Bonniaud  1   2   12 , David Montani  9   10   11   12
Affiliations

Characteristics and outcomes of gemcitabine-associated pulmonary hypertension

Pierre Mouillot et al. ERJ Open Res. .

Abstract

Background: Despite its known cardiac and lung toxicities, the chemotherapy drug gemcitabine has only rarely been associated with pulmonary hypertension (PH), and the underlying mechanism remains unclear. The objective of the present study was to assess the association between gemcitabine and PH.

Methods: We identified incident cases of precapillary PH confirmed by right heart catheterisation in patients treated with gemcitabine from the French PH Registry between January 2007 and December 2022. The aetiology, clinical, functional, radiological and haemodynamic characteristics of PH were reviewed at baseline and during follow-up. A pharmacovigilance disproportionality analysis was conducted using the World Health Organization (WHO) pharmacovigilance database.

Results: We identified nine cases of pulmonary arterial hypertension, either induced (in eight patients) or exacerbated (in one patient) by gemcitabine. Patients exhibited severe precapillary PH, with a median mean pulmonary arterial pressure of 40 (range 26-47) mmHg, a cardiac index of 2.4 (1.6-3.9) L·min-1·m-2 and a pulmonary vascular resistance of 6.3 (3.1-12.6) Wood units. The median time from the initiation of gemcitabine to the onset of PH was 7 (4-50) months, with patients receiving a median of 16 (6-24) gemcitabine injections. Six patients showed clinical improvement upon discontinuation of gemcitabine. In the WHO pharmacovigilance database, we identified a significant signal with 109 cases reporting at least one adverse event related to PH with gemcitabine.

Conclusion: Both clinical cases and pharmacovigilance data substantiate a significant association between gemcitabine use and the onset or worsening of precapillary PH. The observed improvement following the discontinuation of treatment underscores the importance of PH screening in gemcitabine-exposed patients experiencing unexplained dyspnoea.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: X. Jais reports grants or contracts from Acceleron, Janssen, MSD and Bayer HealthCare, outside the submitted work; and payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Janssen and MSD, outside the submitted work. Conflict of interest: L. Savale reports grants or contracts from Bayer, Janssen and Merck, outside the submitted work; and speaker fees from Janssen, outside the submitted work. Conflict of interest: O. Sitbon reports grants or contracts from Acceleron, AOP Orphan, Janssen, GSK and MSD, outside the submitted work; consulting fees from Altavant, Gossamer Bio, Janssen and MSD, outside the submitted work; payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events for AOP Orphan, Janssen, Ferrer and MSD, outside the submitted work; and participation on a Data Safety Monitoring Board or Advisory Board for Acceleron, Altavant, Gossamer Bio, Janssen, MSD and Ferrer, outside the submitted work. Conflict of interest: M. Humbert reports grants or contracts from Acceleron, AOP Orphan, Janssen, Merck and Shou Ti, outside the submitted work; consulting fees from Acceleron, Aerovate, Altavant, AOP Orphan, Bayer, Chiesi, Ferrer, Janssen, Merck, MorphogenIX, Shou Ti, Tiakis and United Therapeutics, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events for Janssen and Merck, outside the submitted work; and participation on a Data Safety Monitoring Board or Advisory Board for Acceleron, Altavant, Janssen, Merck and United Therapeutics, outside the submitted work. Conflict of interest: P. Bonniaud reports a research grant from AstraZeneca, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Sanofi and AstraZeneca, outside the submitted work; support for attending medical and research meetings from AstraZeneca, Novartis, Sanofi, Roche and Boehringer, outside the submitted work; and personal fees for advisory boards from AstraZeneca, Novartis, Sanofi, GSK, Roche and Boehringer, outside the submitted work. Conflict of interest: D. Montani reports grants or contracts from Acceleron, Janssen and Merck MSD, outside the submitted work; consulting fees from Acceleron, Merck MSD, Janssen and Ferrer, outside the submitted work; and speaker fees from Bayer, Janssen, Boehringer, Chiesi, GSK, Ferrer and Merck MSD, outside the submitted work. Conflict of interest: The remaining authors have nothing to disclose.

Figures

FIGURE 1
FIGURE 1
Overall survival from diagnosis of pulmonary hypertension after exposure to gemcitabine. Patients who were censored are represented by a vertical line.
FIGURE 2
FIGURE 2
Network clusters of co-reported cardiopulmonary adverse events with gemcitabine. PH: pulmonary hypertension; ILD: interstitial lung disease.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Mini E, Nobili S, Caciagli B, et al. . Cellular pharmacology of gemcitabine. Ann Oncol 2006; 17: Suppl. 5, v7–12. doi:10.1093/annonc/mdj941 - DOI - PubMed
    1. Zhang XW, Ma YX, Sun Y, et al. . Gemcitabine in combination with a second cytotoxic agent in the first-line treatment of locally advanced or metastatic pancreatic cancer: a systematic review and meta-analysis. Target Oncol 2017; 12: 309–321. doi:10.1007/s11523-017-0486-5 - DOI - PubMed
    1. Shepherd FA, Cormier Y, Burkes R, et al. . Phase II trial of gemcitabine and weekly cisplatin for advanced non-small cell lung cancer. Semin Oncol 1997; 24: 3 Suppl. 8, S8-27–S8-30. - PubMed
    1. Pavlakis N, Bell DR, Millward MJ, et al. . Fatal pulmonary toxicity resulting from treatment with gemcitabine. Cancer 1997; 80: 286–291. doi:10.1002/(SICI)1097-0142(19970715)80:2<286::AID-CNCR17>3.0.CO;2-Q - DOI - PubMed
    1. Roychowdhury DF, Cassidy CA, Peterson P, et al. . A report on serious pulmonary toxicity associated with gemcitabine-based therapy. Invest New Drugs 2002; 20: 311–315. doi:10.1023/A:1016214032272 - DOI - PubMed

LinkOut - more resources