Gemcitabine as maintenance treatment of diffuse pleural mesothelioma: randomized phase II study

Our plain-English summary of Gemcitabine as maintenance treatment of diffuse pleural mesothelioma: randomized phase II study, by M.E. Sobeih, M. Helal, M. Yahia, et al (BMC Cancer, 2026).

The study

• Authors: M.E. Sobeih, M. Helal, M. Yahia, O. Khorshid
• Journal: BMC Cancer
• Published: 2026;26(1)
• Type of article: Randomized trial
• Read it: PubMed · Publisher · Free full text

Abstract

BACKGROUND: Diffuse Pleural Mesothelioma (DPM) is an aggressive cancer with limited treatment options and a poor prognosis. Maintenance therapy has emerged as a potential strategy to delay disease progression following first-line chemotherapy. This study evaluates the efficacy and safety of gemcitabine maintenance therapy compared to best supportive care (BSC) in patients with unresectable DPM. METHODS: This single-center, randomized, phase II, open-label trial included 64 patients with unresectable DPM who achieved a complete/partial response or stable disease after first-line platinum-based chemotherapy. They were randomized 1:1 to receive gemcitabine maintenance therapy (GEM group, n = 32) or BSC (BSC group, n = 32). Progression-free survival (PFS) was the primary endpoint, while overall survival (OS) and toxicity were secondary endpoints. RESULTS: Gemcitabine maintenance therapy significantly improved PFS (median: 6.2 months vs. 2.8 months; HR: 4.33, 95% CI: 2.48–7.56, p < 0.001). However, no significant difference in OS was observed between the GEM and BSC groups (p = 0.155). Performance status (PS) at randomization and histological type were significant prognostic factors for survival. The GEM group experienced higher rates of hematological toxicities, while the BSC group reported more dyspnea, fatigue, and chest pain. No grade 3 or 4 toxicities were observed. CONCLUSION: Gemcitabine maintenance therapy effectively delays disease progression in patients with unresectable DPM, with a manageable toxicity profile. However, its impact on OS is limited. Performance status and histological type remain critical factors in predicting treatment outcomes. TRIAL REGISTRATION: ClinicalTrials.gov (ID NCT07411144, Date 1322026).

In plain English

This randomized, open-label phase II trial at the National Cancer Institute, Cairo University, Egypt (March 2020 to 2023) enrolled 64 patients with unresectable diffuse pleural mesothelioma. All had disease that had responded or stayed stable after first-line platinum-based chemotherapy. Thirty-two received gemcitabine maintenance plus best supportive care, and 32 best supportive care alone. Asbestos exposure was not reported. Median progression-free survival (time from randomization until disease worsening or death) was 6.2 months with gemcitabine and 2.8 months with supportive care alone. The hazard ratio for supportive care alone compared with gemcitabine was 4.33 (95% CI 2.48–7.56). Overall survival did not differ significantly between the groups (p = 0.155). Poorer performance status, non-epithelioid tumors and fewer first-line chemotherapy cycles were associated with worse overall survival. Anemia, leucopenia and nausea were more common with gemcitabine. Dyspnea, fatigue and chest pain were more common with supportive care alone. No grade 3 or 4 toxicity occurred. More supportive-care patients had poorer performance status at the start. The authors concluded that gemcitabine maintenance delays progression with manageable toxicity but has limited impact on overall survival. They named the small sample and single-center design as limitations.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Single-center, randomized (1:1), open-label, parallel-group phase II trial comparing gemcitabine maintenance therapy with best supportive care
• Who was studied: 64 patients with histologically proven unresectable diffuse pleural mesothelioma treated at the National Cancer Institute, Cairo University, Egypt, March 2020 to 2023. All had a complete or partial response or stable disease after four to six cycles of first-line platinum-based chemotherapy. 32 were assigned to the gemcitabine group and 32 to the best supportive care group.
• Exposure: No asbestos exposure was assessed. The treatment compared was gemcitabine 1000 mg/m2 intravenously on days 2 and 8 of a 21-day cycle plus best supportive care, versus best supportive care only.
• Main results:
  • Progression-free survival was measured from randomization until the first documented progression, death, or end of follow-up.
  • Median progression-free survival was 6.2 months in the gemcitabine group versus 2.8 months in the best supportive care group.
  • Progression-free survival was significantly better in the gemcitabine group. The hazard ratio of 4.33 (95% CI 2.48–7.56, p less than 0.001) is for best supportive care alone compared with gemcitabine.
  • Gemcitabine maintenance did not significantly affect overall survival compared with best supportive care (p = 0.155).
  • Across all 64 patients, overall survival was worse in three groups: patients with performance status II (HR 2.67, p = 0.002), patients with non-epithelioid tumors (HR 3.85, p = 0.001), and patients who received 4–5 rather than six cycles of first-line chemotherapy (HR 2.52, p = 0.006).
  • Patients with performance status II at randomization had worse progression-free survival than those with performance status I (HR 1.83, 95% CI 1.06–3.16, p = 0.028).
  • Hematological toxicities were more frequent in the gemcitabine group: anemia in 28 of 32 (87.5%), leucopenia in 19 of 32 (59.4%) and nausea in 12 of 32 (37.5%), versus none in the best supportive care group.
  • In the best supportive care group, dyspnea, fatigue and chest pain each occurred in 93.8% of patients, significantly more than in the gemcitabine group (p less than 0.001).
  • No grade 3 or 4 toxicity occurred in either group.
  • At baseline the groups differed significantly in body mass index and performance status. Performance status II applied to 7 of 32 (21.9%) gemcitabine patients and 15 of 32 (46.9%) supportive care patients. The authors state these differences were considered in the survival analysis.
• The authors' conclusion: The authors concluded that gemcitabine maintenance therapy delays disease progression in unresectable diffuse pleural mesothelioma with manageable toxicity, but its impact on overall survival is limited. They added that performance status and histological type remain critical in predicting outcomes.
• Limitations the authors state:
  • The relatively small sample size may limit how widely the findings apply.
  • The study was conducted at a single center.
  • No validated quality-of-life questionnaire was used, so patients' subjective well-being after treatment was not assessed.
  • The lack of a significant overall survival improvement raises questions about long-term benefit.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Gemcitabine, Pleural Mesothelioma, Prognosis, Disease Progression, Chemotherapy, Unresectable, Progression-Free Survival, Overall Survival.

Related studies

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• A phase II trial of prolonged, continuous infusion of low-dose gemcitabine plus cisplatin in patients with advanced malignant pleural mesothelioma — O. Arrieta, D. López-Macías, et al. (2014)
• BAP1 Status Determines the Sensitivity of Malignant Mesothelioma Cells to Gemcitabine Treatment — A. Guazzelli, P. Meysami, et al. (2019)
• The role of gemcitabine in the treatment of malignant mesothelioma — H.L. Kindler, J.P. van Meerbeeck (2002)
• Randomized Study of Maintenance Pemetrexed Versus Observation for Treatment of Malignant Pleural Mesothelioma: CALGB 30901 — A.Z. Dudek, X. Wang, et al. (2020)
• Gemcitabine reactivates epigenetically silenced genes and functions as a DNA methyltransferase inhibitor — S.G. Gray, A.M. Baird, et al. (2012)

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