Epirubicin in malignant mesothelioma: a phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group

Our plain-English summary of Epirubicin in malignant mesothelioma: a phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group, by K. Mattson, G. Giaccone, A. Kirkpatrick, et al (Journal of Clinical Oncology, 1992).

The study

• Authors: K. Mattson, G. Giaccone, A. Kirkpatrick, D. Evrard, L. Tammilehto, F.J. van Breukelen, H.T. Planteydt, N. van Zandwijk
• Journal: Journal of Clinical Oncology
• Published: 1992;10(5):824-8
• Cited by: 54 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: The doxorubicin analog, epirubicin (EPI), was tested in patients with malignant mesothelioma.

Patients And Methods: Sixty-three patients with malignant mesothelioma were given EPI 110 mg/m2 every 3 weeks. Histology was reviewed and confirmed by a pathology panel. On the basis of unconvincing or wrong histology, insufficient material or cytology only, nine cases were considered ineligible for the study. None of the patients had received prior chemotherapy.

Results: The main side effects were myelosuppression, alopecia, and gastrointestinal toxicity. Tumor response, assessed by computed tomographic (CT) scans, was assessable in 48 patients. Seven patients (15%) achieved a partial response that lasted a median of 37 weeks; 19 patients had stable disease, and 22 patients progressed on treatment. Median survival time was 40 weeks from the start of chemotherapy, and the median survival of responding patients was 87 weeks. One responding patient is still alive and free of relapse 4 years from the start of chemotherapy.

Conclusion: We conclude that further testing of EPI in malignant mesothelioma is warranted.

In plain English

This phase II trial by the EORTC Lung Cancer Cooperative Group tested epirubicin, a chemotherapy drug related to doxorubicin, in patients with malignant mesothelioma who had not had chemotherapy before. It did not study asbestos exposure. Between June 1986 and November 1987, 63 patients from 23 institutions entered the study, and 52 were judged eligible. Patients received epirubicin starting at 110 mg per square metre of body surface every 3 weeks. Of 48 patients whose tumors could be assessed, seven (15%; 95% confidence interval 6.1% to 27.8%) had a partial response lasting a median of 37 weeks. Nineteen had stable disease and 22 progressed. Median survival of eligible patients was 40 weeks from the start of treatment, and 87 weeks among responders. One responder, who also had surgery and radiotherapy, was alive 50 months after starting treatment. There were no life-threatening side effects or treatment deaths. Three patients had significant drops in a heart-function measure but no heart symptoms. The authors described the drug's activity as moderate and concluded that further investigation was warranted.

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 single-drug chemotherapy trial (multicentre, EORTC Lung Cancer Cooperative Group)
• Who was studied: 63 patients with malignant mesothelioma, previously untreated by chemotherapy, entered from 23 institutions between June 1986 and November 1987. 52 were eligible (44 male, 8 female; median age 56.5, range 37 to 73), and 48 were assessable for tumor response.
• Exposure: Not an asbestos exposure study. The exposure studied was treatment with epirubicin, a doxorubicin analog, given intravenously at a starting dose of 110 mg/m2 every 3 weeks. The dose was raised to 130 mg/m2 or reduced according to blood counts.
• Main results:
  • Among 48 assessable patients, 7 had a partial response (15%; 95% exact CI 6.1% to 27.8%), 19 had stable disease, and 22 progressed on treatment.
  • In the responding patients, responses lasted a median of 37 weeks.
  • Among the 52 eligible patients, overall median survival from the start of treatment was 40 weeks, and 33% were alive at 1 year.
  • Among the responding patients, median survival was 87 weeks.
  • One responder was alive 50 months after starting epirubicin. This patient had been treated for residual disease after attempted surgery and also received hemithorax irradiation.
  • There was no life-threatening toxicity and there were no toxic deaths. Grade 3-4 toxicity affected leukocytes in 27% and platelets in 4%. Nausea and vomiting occurred in 92% of patients and were severe in 20%.
  • LVEF was monitored in about half of the patients. Significant drops in left ventricular ejection fraction (from above 55% to below 46%) occurred in three cases, but no symptomatic cardiac toxicity was reported.
• The authors' conclusion: The authors concluded that epirubicin showed moderate activity in malignant mesothelioma, in the range shown by doxorubicin. They concluded that further investigation was warranted, and that although activity was not high, combining it with other active drugs might be worthwhile.
• Limitations the authors state:
  • Because the long-term survivor also had surgery and radiotherapy, the role of epirubicin in that remission is difficult to ascertain.
  • Whether response to epirubicin improved survival in responders could not be established by this study.
  • In the long-term survivor, post-radiation fibrosis was difficult to distinguish from residual disease.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Lung Cancer, Doxorubicin, Histology, Pathology, Cytology, Chemotherapy, Median Overall Survival.

Related studies

• Treatment of malignant mesothelioma with epirubicin and ifosfamide: a phase II cooperative study — M.D. Magri, S. Foladore, et al. (1992)
• Combined epirubicin and interleukin-2 regimen in the treatment of malignant mesothelioma: a multicenter phase II study of the Italian Group on Rare Tumors — S. Bretti, A. Berruti, et al. (1998)
• Progression free survival rate at 9 and 18 weeks predict overall survival in patients with malignant pleural mesothelioma: an individual patient pooled analysis of 10 European Organisation for Research and Treatment of Cancer Lung Cancer Group studies and an independent study validation — B. Hasan, L. Greillier, et al. (2014)
• Comparison of modified Response Evaluation Criteria in Solid Tumors, European Organization for Research and Treatment of Cancer criteria, and PET Response Criteria in Solid Tumors for evaluation of tumor response to chemotherapy and prognosis prediction in patients with unresectable malignant pleural mesothelioma — K. Kitajima, M. Maruyama, et al. (2020)
• 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)
• Paclitaxel for malignant pleural mesothelioma: a phase II study of the EORTC Lung Cancer Cooperative Group — J. van Meerbeeck, C. Debruyne, et al. (1996)

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