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Published on: December 21, 2019
Pemetrexed maintenance therapy in patients with malignant pleural mesothelioma
Debby P M van den Bogaert1, Ellen M Pouw, Gerda van Wijhe
1Department of Pulmonary Medicine, Erasmus MC-Daniel den Hoed Cancer Clinic, Rotterdam, The Netherlands.
Purpose:
To investigate the toxicity and effectiveness of pemetrexed maintenance therapy (PMT) in patients with malignant pleural mesothelioma (MPM).
Patients And Methods:
Eligible were patients with histologically proven advanced MPM, WHO PS 0-2 and adequate hematological, renal and hepatic function in whom during 6 courses of pemetrexed containing induction therapy no disease progression was observed. PMT, 500 mg/m intravenously on day 1 every 3 weeks, was continued until disease progression, unacceptable toxicity, or if continuation was considered to be not in the patient's best interest. Written informed consent was obtained from all patients.
Results:
Of the 27 patients who received induction therapy, 13 were treated with PMT. The median number of PMT courses was 4 (range = 2 to 14). No grade 4 toxicity was observed. Grade 3 neutropenia, leucopenia and anemia occurred 15%, 8% and 8%, respectively. The only non-hematological grade 3 toxicity during PMT was fatigue (15%). During PMT creatinine clearance decreased from 88 (+/-21) ml/min to 77 (+/-26) ml/min (p < 0.05). The reason to stop PMT was disease progression (69%), toxicity (23%) and in patient's best interest (8%). During PMT 23% of the patients with stable disease after induction therapy achieved a partial response. Time to progression and overall survival were 3.4 and 6.0 months versus 8.5 and 17.9 months, respectively (p < 0.0001).
Conclusions:
PMT in MPM patients is non-toxic, well tolerated and although promising effects on TTP and OS are demonstrated, the effectiveness of PMT should be further explored in a prospective randomized clinical trial.
Insights
Pemetrexed maintenance therapy (PMT) for malignant pleural mesothelioma (MPM) shows promise, with improved time to progression and overall survival. This therapy is generally non-toxic and well-tolerated in MPM patients.
Area of Science:
- Oncology
- Clinical Pharmacology
Background:
- Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited treatment options.
- Pemetrexed-based chemotherapy is a standard induction therapy for advanced MPM.
Purpose of the Study:
- To evaluate the toxicity and efficacy of pemetrexed maintenance therapy (PMT) in patients with advanced MPM.
- To assess the impact of PMT on disease progression and survival outcomes.
Main Methods:
- A cohort of 27 advanced MPM patients who completed pemetrexed induction therapy without progression were eligible.
- 13 patients received PMT (500 mg/m every 3 weeks) until disease progression, toxicity, or other clinical reasons.
- Toxicity, response rates, time to progression (TTP), and overall survival (OS) were analyzed.
Main Results:
- No grade 4 toxicity was observed; grade 3 toxicities included neutropenia (15%), leucopenia (8%), anemia (8%), and fatigue (15%).
- Creatinine clearance showed a statistically significant decrease during PMT (p < 0.05).
- PMT demonstrated significant improvements in TTP (8.5 vs 3.4 months) and OS (17.9 vs 6.0 months) compared to historical controls (p < 0.0001).
Conclusions:
- Pemetrexed maintenance therapy (PMT) is a non-toxic and well-tolerated treatment option for MPM patients.
- PMT shows promising efficacy in improving TTP and OS in advanced MPM.
- Further investigation in prospective randomized clinical trials is warranted to confirm the effectiveness of PMT.
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