First-line chemotherapy with liposomal doxorubicin plus cisplatin for patients with advanced malignant pleural mesothelioma: phase II trial

Our plain-English summary of First-line chemotherapy with liposomal doxorubicin plus cisplatin for patients with advanced malignant pleural mesothelioma: phase II trial, by Ó. Arrieta, L.A. Medina, E. Estrada-Lobato, et al (British Journal of Cancer, 2012).

The study

• Authors: Ó. Arrieta, L.A. Medina, E. Estrada-Lobato, N. Hernández-Pedro, G. Villanueva-Rodríguez, L. Martínez-Barrera, E.O. Macedo, V. López-Rodríguez, D. Motola-Kuba, J.F. Corona-Cruz
• Journal: British Journal of Cancer
• Published: 2012;106(6):1027-32
• Cited by: 38 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Chemotherapy based on platinum is the standard treatment for unresectable malignant pleural mesothelioma (MPM). Liposomal doxorubicin (LD) consists of pegylated phospholipid vesicles that encapsulate doxorubicin-enhancing liposome deposition in the tumour. We evaluated the toxicity profile and anti-tumour activity of cisplatin plus LD in untreated patients with MPM, as well as (99m)Tc-LD distribution in MPM lesions after chemotherapy administration.

Methods: A total of 38 patients with non-resectable MPM received LD 40 mg m(-2) and cisplatin 60 mg m(-2) every 21 days. Gamma camera images of (99m)Tc-LD were acquired to evaluate LD accumulation in measurable tumour tissue. The study was registered in Clinical Trials (NCT00886028).

Results: In all, 72% of patients were stage III and 28% were stage IV. Eighty four percent and 16% have high and low risk acording EORTC respectively. The median time to progression was 4.6 months (95% confidence interval (95% CI: 3.4-5.9 months), and median overall survival (OS) was 19.6 months (15.2-37.2 months). Patients that responded to chemotherapy treatment had better survival than patients who did not. Functional physical scales, dysnea, cough, and chest/arm pain demonstrated improvement. The accumulation ratio of LD in tumour and soft tissues vs liver was 0.78±0.16 and 0.29±0.09, respectively. After 1 h of administration, LD uptake in tumour tissue was higher than in soft tissue (P< 0.001).

Conclusion: The combination of LD and cisplatin results in an active therapeutic regimen for unresectable MPM, with an acceptable toxicity profile and improvement in quality of life. (99m)Tc-LD showed higher levels of tumour uptake as compared with surrounding tissues.

In plain English

This phase II trial at two thoracic cancer centres in Mexico City treated 38 consecutive patients with unresectable stage III or IV malignant pleural mesothelioma, none previously given chemotherapy. They received liposomal doxorubicin plus cisplatin every 21 days, up to six cycles. Table 1 lists 23 patients (60.5%) with asbestos exposure. Of 36 patients assessed, 14 had a partial response, 15 stable disease and 7 disease progression. None had a complete response. The results text gave median time to progression as 4.2 months (95% CI 3.4 to 5.9; the opening summary says 4.6) and median overall survival as 19.6 months (95% CI 15.2 to 37.2). The authors reported better survival in responders, but that comparison had a P value of 0.06, above the study's 0.05 significance threshold. There were no treatment-related deaths, and one patient stopped because of side effects. Among the quality-of-life scales, only physical functioning changed significantly. Scans with radiolabelled drug showed higher uptake in tumour than in soft tissue. The authors concluded the combination was active with acceptable toxicity. Because the study was small, they called for phase III trials.

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, including radiolabelled imaging of the drug's distribution
• Who was studied: 38 consecutive patients with unresectable stage III/IV malignant pleural mesothelioma, from two thoracic oncology reference centres in Mexico City, enrolled September 2006 to September 2009. No prior chemotherapy. Table 1 lists 23 (60.5%) with asbestos exposure.
• Exposure: Liposomal doxorubicin 40 mg per square metre plus cisplatin 60 mg per square metre on day 1 of each 21-day cycle, up to six cycles. Radiolabelled (99mTc) liposomal doxorubicin was given in the first cycle only. Asbestos exposure was recorded as a patient characteristic but was not the subject of the study.
• Main results:
  • Of 36 evaluable patients: partial response in 38.9% (14/36), stable disease in 41.6% (15/36), disease progression in 19.4% (7/36)
  • No patient had a complete response
  • All patients: median time to disease progression 4.2 months (95% CI 3.4 to 5.9) and median overall survival 19.6 months (95% CI 15.2 to 37.2), as given in the results text
  • Non-responders had a median survival of 7.7 months (95% CI 2.17 to 38.18). Responders had not reached median overall survival at the time of analysis. P = 0.06.
  • No treatment-related deaths. One patient withdrew because of side effects (neutropaenia without recovery).
  • Two patients had a rise in creatinine and were switched from cisplatin to carboplatin
  • Six responding patients were eligible for surgery, and three had complete cytoreductive surgery
  • Quality of life: physical functioning was the only scale with a statistically significant change (P = 0.045)
  • Imaging 1 hour after infusion: tumour uptake index 0.78 plus or minus 0.16. In 80% of imaged patients, tumour uptake was higher than soft-tissue uptake (0.29 plus or minus 0.09), P less than 0.001.
• The authors' conclusion: The authors concluded that liposomal doxorubicin plus cisplatin was an active combination for malignant pleural mesothelioma with an acceptable toxicity profile.
• Limitations the authors state:
  • A phase II study with a small number of patients. Phase III comparison with cisplatin/pemetrexed or cisplatin/raltitrexed is needed.

Topics

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

Medical terms in this study, explained in our Lexicon: Chemotherapy, Doxorubicin, Cisplatin, Pleural Mesothelioma, Unresectable, Deposition, Clinical Trial, confidence interval.

Related studies

• High liposomal doxorubicin tumour tissue distribution, as determined by radiopharmaceutical labelling with (99m)Tc-LD, is associated with the response and survival of patients with unresectable pleural mesothelioma treated with a combination of liposomal doxorubicin and cisplatin — O. Arrieta, L.A. Medina, et al. (2014)
• Phase II study of first-line bortezomib and cisplatin in malignant pleural mesothelioma and prospective validation of progression free survival rate as a primary end-point for mesothelioma clinical trials (European Organisation for Research and Treatment of Cancer 08052) — M.E. O'Brien, R.M. Gaafar, et al. (2013)
• First-line chemotherapy with pemetrexed plus cisplatin for malignant peritoneal mesothelioma — E. Fujimoto, T. Kijima, et al. (2017)
• JME-001 phase II trial of first-line combination chemotherapy with cisplatin, pemetrexed, and nivolumab for unresectable malignant pleural mesothelioma — Y. Miyamoto, T. Kozuki, et al. (2021)
• A Phase II Trial of First-Line Combination Chemotherapy With Cisplatin, Pemetrexed, and Nivolumab for Unresectable Malignant Pleural Mesothelioma: A Study Protocol — N. Fujimoto, K. Aoe, et al. (2018)
• 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)

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