Gemcitabine as Maintenance Treatment for Diffuse Pleural Mesothelioma

Diffuse pleural mesothelioma (DPM) is an aggressive malignancy with limited therapeutic options and a high risk of early disease progression despite initial response to platinum-based chemotherapy. Although first-line systemic treatment can achieve disease control in a subset of patients, most will experience relapse within a short time interval. Strategies aimed at maintaining disease control after completion of induction chemotherapy are therefore of clinical interest.

Maintenance therapy using a non-cross-resistant cytotoxic agent represents a potential approach to delay tumor progression while preserving acceptable tolerability. Gemcitabine is an antimetabolite chemotherapeutic agent with documented activity in mesothelioma and a manageable safety profile. Its use as switch-maintenance therapy following platinum-based induction treatment may provide continued suppression of tumor growth without overlapping toxicity.

This randomized, open-label, phase II study was designed to evaluate whether gemcitabine maintenance therapy improves progression-free survival compared with best supportive care alone in patients with unresectable DPM who achieved complete response, partial response, or stable disease after first-line chemotherapy. Patients were randomized in a 1:1 ratio to receive either gemcitabine maintenance therapy plus best supportive care or best supportive care alone.

The study also explores the impact of maintenance therapy on overall survival and evaluates treatment-related toxicity. In addition, clinical and pathological factors such as performance status and histological subtype are assessed for their prognostic relevance. The results of this trial aim to inform clinical decision-making regarding post-induction management strategies in unresectable diffuse pleural mesothelioma.

Inclusion criteria

• Age ≥ 18 years

Histologically confirmed unresectable diffuse pleural mesothelioma

Complete response, partial response, or stable disease after 4-6 cycles of first-line platinum-based chemotherapy, according to modified RECIST (mRECIST) criteria

Last dose of first-line chemotherapy administered within 60 days prior to randomization

Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Life expectancy of at least 12 weeks

Adequate bone marrow function

Adequate hepatic function

Adequate renal function

Ability to provide written informed consent

Exclusion criteria

• Prior extra-pleural pneumonectomy

Evidence of active brain or leptomeningeal metastases

Weight loss >10% within 6 weeks prior to enrollment

Clinically significant ascites

Known hypersensitivity or intolerance to gemcitabine

Receipt of non-palliative radiotherapy within 3 weeks before initiation of study treatment