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Association Between Proton Pump Inhibitors and Hematologic Toxicity of Pemetrexed

NCT03537833 · Status: COMPLETED · Type: OBSERVATIONAL · Enrollment: 172

Last updated 2022-02-14

No results posted yet for this study

Summary

Pemetrexed is a multi-folate inhibitor approved in the treatment of non-small cell lung cancer (NSCLC) and pleural mesothelioma. Its toxicity profile is mainly hematologic (anemia, neutropenia and thrombopenia) and can be limiting when \> grade 2 according to NCI-CTCAE criteria. First clinical trials highlighted hematologic toxicity, especially anemia, which was reduced by decreasing pemetrexed dosage from 600 to 500 mg/m² Q3W and by adding systematic vitamin supplementation (B9/B12). Despite this, incidence of hematological toxicity remains frequent with anemia occurring in more than 20% of patients treated by pemetrexed in combination. Methotrexate, a well-known antineoplastic drugs used in several cancer and non-cancer disease conditions can also induced severe hematologic toxicity in case of methotrexate-reduced elimination and, as a consequence, its accumulation. For example, the elimination of methotrexate is mediated by tubular secretion through type 1 and type 3 organic anion transport (hOAT1 and hOAT3). Association with drugs that inhibits hOATs can induced a hematological toxicity caused by methotrexate accumulation. Among these, proton pump inhibitors (PPIs) are known to inhibit hOATs. The drug interaction that results from their combination with methotrexate is clinically relevant and lead to an increased hematological toxicity. However, hypothetical drug interaction between PPIs and pemetrexed is unknown while pemetrexed seems to be mostly eliminated by hOAT3 (11-fold higher than methotrexate). One study revealed lansoprazole to inhibits in vitro hOAT3. This same study investigates in a retrospective chart patients treated by pemetrexed and the study found a significant association between combination with PPI and hematological toxicity by pemetrexed. Unfortunately this study lacks of relevant methodology and suffered from its retrospective chart. This potential drug interaction must be a real concern for oncologists and clinical pharmacists. The investigators aim to investigate the potential association between PPIs and pemetrexed combination and the incidence of hematological toxicity in a multicenter and prospective study.

Conditions

  • Patients With Non-small Cell Lung Cancer (NSCLC) and Pleural Mesothelioma and Treated With a Pemetrexed-based Chemotherapy

Interventions

OTHER

pemetrexed-related hematological toxicity

hematological toxicity will be found on biologic data the day or the day before chemotherapy. Classification will based on NCI-CTCAE criteria

Sponsors & Collaborators

  • CHU de Reims

    lead OTHER

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2018-05-02
Primary Completion
2021-02-18
Completion
2022-02-11

Countries

  • France

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03537833 on ClinicalTrials.gov