Treatment of malignant pleural mesothelioma with carboplatin, liposomized doxorubicin, and gemcitabine: a phase II study

Our plain-English summary of Treatment of malignant pleural mesothelioma with carboplatin, liposomized doxorubicin, and gemcitabine: a phase II study, by G. Hillerdal, J.B. Sorensen, S. Sundström, et al (Journal of Thoracic Oncology, 2008).

The study

• Authors: G. Hillerdal, J.B. Sorensen, S. Sundström, H. Riska, A. Vikström, A. Hjerpe
• Journal: Journal of Thoracic Oncology
• Published: 2008;3(11):1325-31
• Cited by: 37 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Malignant pleural mesothelioma has a poor prognosis and there is limited effect of treatment. The Nordic Mesothelioma groups decided in the year 2000 to investigate a combination of liposomized doxorubicin, carboplatin, and gemcitabine for this disease in a phase II study.

Methods: From January 2001, to December 2003, 173 evaluable patients with biopsy-verified malignant mesothelioma were included. Two patients were lost to follow-up, but all the others were followed for at least 4 years or until death.

Results: Toxicity was fairly low. There were 56 responses (32.4%), of which 2 were complete; the median time to progression was 8.6 months, and the median overall survival was 13 months. Some patients had their responses 4 to 6 months after last treatment. For 116 patients with epitheloid subtype, median survival was 17 months. A subgroup of these patients with good performance status, early stage, and age 70 years or less, showed a median survival of 22 months.

Conclusion: The treatment yields good results with a high number of responses and long survival, and a low toxicity. The long survival of the epitheloid subgroup with good prognostic factors is as good as or even better than some studies on "radical" surgery or multimodal treatment, underlining the need of randomized studies to evaluate such treatment options.

In plain English

This phase II study by the Nordic mesothelioma groups ran at 19 centers in Sweden, Norway, Denmark and Finland. It tested carboplatin, gemcitabine and pegylated liposomal doxorubicin together in malignant pleural mesothelioma. There was no comparison group; patients were enrolled from January 2001 to December 2003. Of 184 included, 173 were evaluable; 127 of these reported asbestos exposure, mostly at work. Overall, 56 patients (32.4%) had a tumor response, 2 of them complete. Median survival was 13 months for the whole group. It was 17 months for the 116 epitheloid patients, 8.5 months for mixed and 4.5 months for sarcomatoid subtypes. Epitheloid patients aged 70 or under with early stage and good performance status had a median survival of 22 months. Side effects were mainly blood-related, and three patients died of neutropenic sepsis. In 4 patients, all with the epitheloid subtype, responses appeared 4 to 6 months after the last course. The authors concluded the treatment was feasible with low toxicity. They said a phase II study could not show the treatment superior to any other.

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: Multicenter phase II (single-arm, uncontrolled) chemotherapy treatment study
• Who was studied: 173 evaluable patients with biopsy-verified malignant pleural mesothelioma (184 enrolled, 11 excluded). They were enrolled January 2001 to December 2003 at 19 centers: 84 from Sweden, 50 from Norway, 29 from Denmark and 10 from Finland. Mean age was 62.8 years (range 38 to 83), and 16 were women. 127 of the 173 patients reported asbestos exposure, in most cases occupational. The article prints this as 74.4%, but 127 of 173 is 73.4%.
• Exposure: The treatment studied was carboplatin, gemcitabine and pegylated liposomal-encapsulated doxorubicin (Caelyx). It was given every 3 weeks for 6 cycles, with dose reductions after cycle three. Asbestos exposure was recorded as a patient characteristic but was not what the study tested.
• Main results:
  • Whole group: 56 responses (32.4%), of which 54 were partial and 2 were complete
  • Response rates by subtype: epitheloid 41 partial and 2 complete (37.1%); mixed 5 partial (23.8%); sarcomatoid 5 partial (20.8%)
  • Whole group: median survival 13 months; 1-year survival 52.3%
  • Median survival by subtype: epitheloid (n = 116) 17 months; sarcomatoid (n = 24) 4.5 months; mixed (n = 21) 8.5 months
  • Epitheloid patients with stage 1 to 2 disease, performance status 0 to 1 and age 70 or under had a median survival of 22 months
  • Median time to progression: 8.2 months for all patients; 10 months for epitheloid; 6 months for mixed and 4 months for sarcomatoid
  • Three patients died of neutropenic sepsis (2 after the first course, 1 after the fourth); these were the only treatment-related deaths. Toxicity was mainly hematological.
  • Thirteen patients (7.5% of all, 11.2% of the epitheloid group) were alive more than 4 years (48 months)
  • In 4 patients, all with the epitheloid subtype, responses were seen 4 to 6 months after the last course
  • Among the 116 epitheloid patients, median survival was 25 months for women and 17 months for men
  • Survival did not differ by whether pleurodesis had been performed before treatment
• The authors' conclusion: The authors concluded that the combination was feasible, had low toxicity and gave a high number of responses. They said it was associated with good time to progression and survival. They also concluded that randomized studies are needed to evaluate surgical and multimodality treatment.
• Limitations the authors state:
  • As a phase II study it cannot show the treatment is superior to any other. That would need a phase III study, which the Nordic groups could not afford.
  • Data on second-line and later treatment were not systematically recorded
  • Patients with the earliest disease and best performance status were operated on rather than enrolled, which makes comparison with surgical studies difficult
  • The studies compared with this one in the discussion are not directly comparable because patient selection differs

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Carboplatin, Doxorubicin, Gemcitabine, Prognosis, Mesothelioma, Biopsy, Median Overall Survival.

Related studies

• Third-line chemotherapy with carboplatin, gemcitabine and liposomised doxorubicin for malignant pleural mesothelioma — V.A. de Lima, J.B. Sørensen (2015)
• Phase I combination study of the PARP inhibitor veliparib plus carboplatin and gemcitabine in patients with advanced ovarian cancer and other solid malignancies — H.J. Gray, K. Bell-McGuinn, et al. (2018)
• DNA repair polymorphisms and treatment outcomes of patients with malignant mesothelioma treated with gemcitabine-platinum combination chemotherapy — N. Erčulj, V. Kovač, et al. (2012)
• Phase II study of gemcitabine plus docetaxel as second-line treatment in malignant pleural mesothelioma: a single institution study — I. Tourkantonis, N. Makrilia, et al. (2011)
• Carboplatin plus pemetrexed as first-line treatment of patients with malignant pleural mesothelioma: a phase II study — N. Katirtzoglou, I. Gkiozos, et al. (2010)
• Gemcitabine with or without ramucirumab as second-line treatment for malignant pleural mesothelioma (RAMES): a randomised, double-blind, placebo-controlled, phase 2 trial — C. Pinto, P.A. Zucali, et al. (2021)

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