Epirubicin and gemcitabine as first-line treatment in malignant pleural mesothelioma

Our plain-English summary of Epirubicin and gemcitabine as first-line treatment in malignant pleural mesothelioma, by L. Portalone, A. Antilli, F. Nunziati, et al (Tumori, 2005).

The study

• Authors: L. Portalone, A. Antilli, F. Nunziati, C. Crispino, F. de Marinis, L. Friggeri, A. Lombardi, V. Lorusso, P. Pronzato, D. Sambiasi, M. Signora, Associazione Italiana Pneumologi Ospedalieri Thoracic Oncology Study Group
• Journal: Tumori
• Published: 2005;91(1):15-8
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma represents a rare disease, for which chemotherapy actually remains unsatisfactory. From August 1998 to November 2001, 28 chemo-radio-immunonaive patients were consecutively enrolled in the trial: 22/6 males/females; median age 63 years (range, 45-79); median ECOG PS 1 (range, 0-2). They were treated with epirubicin (100 mg/m2 iv on day 1) plus gemcitabine (1000 mg/m2 iv on days 1 and 8) every 4 weeks for 6 cycles. Patients who responded to chemotherapy (n = 6) were subsequently treated with interleukin-2 (4,500,000 IU) subcutaneously every other day, until progression. A total of 124 epirubicin-gemcitabine cycles were administered (median, 6/patient; range, 2-6). Twenty-six patients were evaluated for toxicity. According to WHO criteria, we observed grade III-IV hematological and gastrointestinal toxicity respectively in 3 patients (11%) and 1 patient (3%). No red cell transfusions were required and no toxic deaths occurred. Two patients (8%) could not be evaluated for response (no therapy performed). According to WHO criteria, the final responses were: partial in 4 patients (14%), stable disease in 19 patients (69%), and progression in 3 patients (10%). In 26 patients, the median survival was 55 weeks (range, 7-222) and median time to progression 30 weeks (range, 4-156). At the time of this writing, no patient is alive. The 1-year survival was 32%, 2-year survival 11%, and 4% at 3 and 4 years. All patients were at stage III, and time to progression was 58 weeks and survival 63.5 weeks, without any toxicity. This multi-center phase II clinical trial showed that epirubicin plus gemcitabine, as a first-line treatment in malignant pleural mesothelioma, has promising activity with a good tolerability profile and symptom palliation. The role of interleukin-2 in maintenance therapy for malignant pleural mesothelioma is encouraging and requires further study.

In plain English

This Italian multicenter phase II trial tested epirubicin plus gemcitabine chemotherapy as first treatment for malignant pleural mesothelioma. Side effects were its main end point. From August 1998 to November 2001, 28 patients (22 men, 6 women, median age 63) with no prior chemotherapy, immunotherapy or radiotherapy, apart from surgical-site irradiation, were enrolled. Two refused therapy, so 26 were evaluated. The article does not discuss asbestos exposure. Of the 26, 4 had a partial response, 19 had stable disease and 3 had disease progression. The article gives two different sets of medians. Its abstract, table and discussion give 30 weeks to progression and 55 weeks survival, while its results text gives 41 and 51 weeks. Survival was 32% at 1 year, 11% at 2 years and 4% at 3 and 4 years. Severe blood-related side effects occurred in 2 patients, and there were no treatment-related deaths. Six patients later received interleukin-2. The authors concluded that the regimen showed interesting activity and a good toxicity profile. They said no conclusions could be drawn about interleukin-2 because so few patients received it.

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 clinical trial of chemotherapy (single arm, no comparison group), with toxicity as the primary end point
• Who was studied: 28 patients with malignant pleural mesothelioma (22 males, 6 females; median age 63, range 45-79), enrolled at hospitals in Italy from August 1998 to November 2001. Eligibility excluded previous chemotherapy, immunotherapy and radiotherapy, except irradiation at a surgical site. 26 started treatment and were evaluated. Stage III in 15 (54%) and stage IV in 7 (25%); epithelial histotype in 23 (82%).
• Exposure: Asbestos exposure is not reported. The treatment studied was epirubicin 100 mg/m2 on day 1 plus gemcitabine 1000 mg/m2 on days 1 and 8, every 4 weeks for 6 cycles (124 cycles given in total). Some responding or stable patients then received interleukin-2 at 4,500,000 IU subcutaneously three times a week until progression.
• Main results:
  • Among the 26 treated patients: 4 partial responses (14%), 19 stable disease (68%), 3 disease progressions (11%)
  • Median time to progression 30 weeks and median survival 55 weeks (as given in the article's abstract, Table 3 and discussion)
  • The results section instead reports median time to progression of 41 weeks (range 4-120; 95% CI 33-61) and median survival of 51 weeks (range 7-172; 95% CI 45.5-85.5)
  • Survival was 32% at 1 year, 11% at 2 years, and 4% at 3 and 4 years
  • Hematological toxicity (mainly low white cell counts) was grade I to II in 10 patients (38%) and grade III to IV in 2 patients (8%). Gastrointestinal toxicity was grade III in 1 patient (4%). No transfusions, toxic deaths or cardiac toxicity were reported.
  • Six patients with stage III epithelial disease (3 partial response, 3 stable disease) who went on to interleukin-2 had a median time to progression of 58 weeks and median survival of 63.5 weeks, without further toxicity
• The authors' conclusion: The authors concluded that epirubicin plus gemcitabine showed interesting activity and a good toxicity profile in malignant mesothelioma. Noting that pemetrexed is the accepted first-line chemotherapy, they said the combination may be a good alternative therapy.
• Limitations the authors state:
  • No conclusions can be drawn about interleukin-2 maintenance because only a small number of patients received it; the authors said a large randomized study would be 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: Gemcitabine, Pleural Mesothelioma, Chemotherapy, Median Survival, Clinical Trial.

Related studies

• 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)
• 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)
• 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)
• Second-line gemcitabine-based chemotherapy regimens improve overall 3-year survival rate in patients with malignant pleural mesothelioma: a multicenter retrospective study — H. Mutlu, S. Gündüz, et al. (2014)
• 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)
• Gemcitabine and vinorelbine as second-line or beyond treatment in patients with malignant pleural mesothelioma pretreated with platinum plus pemetrexed chemotherapy — G. Toyokawa, M. Takenoyama, et al. (2014)

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