A phase II trial of prolonged, continuous infusion of low-dose gemcitabine plus cisplatin in patients with advanced malignant pleural mesothelioma

Our plain-English summary of A phase II trial of prolonged, continuous infusion of low-dose gemcitabine plus cisplatin in patients with advanced malignant pleural mesothelioma, by O. Arrieta, D. López-Macías, V.O. Mendoza-García, et al (Cancer Chemotherapy and Pharmacology, 2014).

The study

• Authors: O. Arrieta, D. López-Macías, V.O. Mendoza-García, L. Bacon-Fonseca, W. Muñoz-Montaño, E.O. Macedo-Pérez, S. Muñiz-Hernández, M. Blake-Cerda, J.F. Corona-Cruz
• Journal: Cancer Chemotherapy and Pharmacology
• Published: 2014;73(5):975-82
• Cited by: 27 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: Low-dose, prolonged infusion of gemcitabine has effects similar to standard doses in several cancers. We evaluated the toxicity and efficacy of low-dose gemcitabine in prolonged infusion plus cisplatin in patients with advanced pleural mesothelioma.

Methods: Patients with mesothelioma received gemcitabine (250 mg/m(2)) in a 6-h infusion plus cisplatin (35 mg/m(2)) on days 1 and 8 every three weeks. We used the modified response evaluation criteria in solid tumours. This study is registered in clinical trials (NCT01869023).

Results: We included 39 patients; 82.1 % were low risk according to the European Organisation for Research and Treatment of Cancer prognostic group. Partial response was observed in 53.8 % (21/39), stable disease in 33.3 % (13/39) and progression in 12.8 % (5/39). The median progression-free survival was 6.9 months (95 % CI 3.2-10.6 months), and the associated factors were the EORTC risk and histology. The median overall survival was 20.7 months (95 % CI 10.7-30.8 months). The functional, physical and emotional roles and dyspnoea, insomnia and pain symptom scales improved. The most commonly graded 3/4 side effects were neutropenia (24.4 %), lymphopenia (14.6 %), thrombocytopenia (14.7 %) and anaemia (12.2 %).

Conclusions: Low-dose, prolonged gemcitabine infusion plus cisplatin has acceptable toxicity and high efficacy with improved quality of life, representing an affordable regimen for the low-income population.

In plain English

This phase II trial at the Instituto Nacional de Cancerología, Mexico City, treated 41 consecutive patients with previously untreated, unresectable stage III or IV malignant pleural mesothelioma from January 2009 to July 2013. Patients received low-dose gemcitabine 250 mg/m2 as a 6-hour infusion plus cisplatin 35 mg/m2 on days 1 and 8 of three-week cycles. Asbestos exposure was reported by 51.2% of patients. Of 39 assessable patients, 53.8% (21/39; 95% CI 38.1 to 70.2) had a partial response, 33.3% (13/39; 95% CI 17.3 to 47.5) stable disease and 12.8% (5/39; 95% CI 2.5 to 24.5) progression. None had a complete response. Median progression-free survival was 6.9 months (95% CI 3.2 to 10.6) and median overall survival 20.7 months (95% CI 10.7 to 30.8). The authors found no association between overall survival and asbestos exposure. The most common severe (grade 3 or 4) side effect was neutropenia (24.4% of patients). No treatment-related deaths were recorded. Several quality-of-life scales improved after two cycles, while nausea and vomiting increased. The authors concluded the regimen has acceptable toxicity and high efficacy and is affordable for low-income patients.

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: Phase II clinical trial of a chemotherapy regimen (single treatment group)
• Who was studied: 41 consecutive patients with unresectable stage III/IV malignant pleural mesothelioma, without previous treatment, at the Instituto Nacional de Cancerología, Mexico City, January 2009 to July 2013. 39 were evaluable for response.
• Exposure: The treatment studied was gemcitabine 250 mg/m2 in a 6-hour infusion plus cisplatin 35 mg/m2 on days 1 and 8 every 3 weeks, for up to six cycles. Asbestos exposure was reported by 51.2% of patients (21 of 41). No fiber types were given.
• Main results:
  • Among 39 evaluable patients, 53.8% (21/39; 95% CI 38.1 to 70.2) had a partial response.
  • Among 39 evaluable patients, 33.3% (13/39; 95% CI 17.3 to 47.5) had stable disease.
  • Among 39 evaluable patients, 12.8% (5/39; 95% CI 2.5 to 24.5) had disease progression.
  • Among 39 evaluable patients, the disease control rate was 87.1% (34/39; 95% CI 75.5 to 97.5).
  • No patient had a complete response.
  • None of the 5 patients with sarcomatoid histology responded (0/5, 0%), compared with 60% (21/35) of patients with epithelial histology (p 0.036).
  • Among patients in the EORTC low-risk group, 61.8% (21/34) responded. None of the high-risk patients responded (p 0.014).
  • Median progression-free survival for all patients was 6.9 months (95% CI 3.2 to 10.6 months).
  • Median progression-free survival was 8.5 months (95% CI 4.7 to 12.4) for patients with epithelioid histology versus 3.8 months (95% CI 0.18 to 7.5) for those with non-epithelioid histology (p 0.006).
  • Median overall survival for all patients was 20.7 months (95% CI 10.7 to 30.8 months).
  • Median overall survival was 20.7 months in the EORTC low-risk group versus 7.5 months in the high-risk group. The authors described this as a not significant tendency (p 0.079).
  • No association was found between overall survival and age, gender, asbestos exposure, smoking status, disease stage or histology.
  • Grade 3 or 4 side effects included neutropenia in 24.4% of patients, thrombocytopenia in 14.7% and anaemia in 12.2%. Eight patients (19.5%) needed a dose reduction.
  • No treatment-related deaths and no withdrawals because of side effects were recorded.
  • After two cycles, the physical, functional and emotional role scales and the pain, dyspnoea and insomnia symptom scales improved with statistical significance. Nausea/vomiting increased (p = 0.012).
  • Nine patients (21.9%) underwent surgery, none of which was extrapleural pneumonectomy.
• The authors' conclusion: The authors concluded that low-dose, prolonged-infusion gemcitabine plus cisplatin shows acceptable toxicity and high efficacy, improves quality of life, and is an affordable regimen for the low-income population.

Topics

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

Medical terms in this study, explained in our Lexicon: Gemcitabine, Cisplatin, Pleural Mesothelioma, Mesothelioma, Clinical Trial, Progression-Free Survival, Histology, Median Overall Survival.

Related studies

• A phase II trial of low-dose gemcitabine in a prolonged infusion and cisplatin for malignant pleural mesothelioma — V. Kovac, M. Zwitter, et al. (2012)
• Efficacy, Safety, and Cost-Minimization Analysis of Continuous Infusion of Low-Dose Gemcitabine Plus Cisplatin in Patients With Unresectable Malignant Pleural Mesothelioma — O. Arrieta, W. Muñoz-Montaño, et al. (2021)
• Switch-maintenance gemcitabine after first-line chemotherapy in patients with malignant mesothelioma (NVALT19): an investigator-initiated, randomised, open-label, phase 2 trial — C.J. de Gooijer, V. van der Noort, et al. (2021)
• A dose-finding study of gemcitabine and vinorelbine in advanced previously treated malignancies — J.P. Delord, E. Raymond, et al. (2000)
• In vitro anti-mesothelioma activity of cisplatin-gemcitabine combinations: evidence for sequence-dependent effects — I. Zanellato, C.D. Boidi, et al. (2011)
• Nintedanib in combination with pemetrexed and cisplatin for chemotherapy-naive patients with advanced malignant pleural mesothelioma (LUME-Meso): a double-blind, randomised, placebo-controlled phase 3 trial — G.V. Scagliotti, R. Gaafar, et al. (2019)

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