Platinum-based doublet chemotherapy in pre-treated malignant pleural mesothelioma (MPM) patients: a mono-institutional experience

Our plain-English summary of Platinum-based doublet chemotherapy in pre-treated malignant pleural mesothelioma (MPM) patients: a mono-institutional experience, by G. Pasello, S. Nicotra, G. Marulli, et al (Lung Cancer, 2011).

The study

• Authors: G. Pasello, S. Nicotra, G. Marulli, F. Rea, L. Bonanno, P. Carli, C. Magro, A. Jirillo, A. Favaretto
• Journal: Lung Cancer
• Published: 2011;73(3):351-5
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: The major clinical problems of MPM management are the short duration of response and the early relapse. Currently, after the first-line standard pemetrexed/platinum combination there is not a defined regimen for the second line treatment of MPM, and the clinical benefits in fit patients are uncertain. We analyzed the feasibility of gemcitabine/platinum chemotherapy in pretreated MPM patients.

Methods: Eligible patients should have relapsed after first-line chemotherapy with pemetrexed plus cisplatin (24%) or carboplatin (76%); 53% of the patients had previously received trimodality treatment, 18% neoadjuvant chemotherapy followed by pleurectomy/decortication, 29% were inoperable. Patients had to have PS=0-2, adequate organ function, measurable disease. Chemotherapy was gemcitabine 1000 mg/m(2) days 1, 8 associated to the alternative platinum compound respect to 1st line, i.e. cisplatin 75 mg/m(2) or carboplatin AUC 5 day 1 every 3 weeks, for 3-6 cycles. Baseline staging and reassessment after cycles 3 and 6 were performed with CT-scan.

Results: Since 2006 17 relapsed MPM patients were referred to our centre. Patients were 12 males and 5 females; median age: 61 years (range 47-74); histology: 12 epithelial, 4 sarcomatoid and 1 biphasic. PS 1-2 (15:2). The combination of gemcitabine with carboplatin/cisplatin was administered as second line treatment in 13 (76%) patients, as third line in 4 (24%) patients. Two patients were lost to follow-up without re-evaluation, therefore radiologic and clinical response was assessable in 15 (88%) patients. Among evaluable patients 10 (67%) showed stable disease and 5 (33%) progressive disease. Symptoms improved in 8 (53%) cases. In the intent-to-treat population median survival was 28 weeks (range 13-168) and median time-to-treatment failure 15 weeks (range 3-75). Toxicity profile showed 2 (13%) grade 4 and 6 (40%) grade 3 thrombocytopenia, 4 (27%) grade 3 leucopenia, 3 (20%) grade 3 anaemia and 6 (40%) of grade 3 neutropenia. Grade 3 non haematological toxicities were nausea (14%) and asthenia (21%).

Conclusion: Gemcitabine-platinum regimens are able to control symptoms and disease progression with a modest toxicity profile. The present results from a small series of patients should be confirmed by a prospective trial in a larger cohort of patients.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

In plain English

This was a retrospective analysis from Padua, Italy, of 17 patients with malignant pleural mesothelioma who relapsed after first-line chemotherapy with pemetrexed plus cisplatin or carboplatin. Since 2006 they received gemcitabine with the platinum drug not used in their first-line treatment: 13 as second-line treatment, 4 as third-line. The study examined treatment, not asbestos exposure. Of 15 patients who could be assessed, none had a partial response. Ten (67%; 95% CI 38–88%) had stable disease and 5 (33%; 95% CI 12–62%) had progressive disease. Symptoms improved in 8 of the 15 (53%; 95% CI 26–79%). Across all 17 patients, median survival was 28 weeks and median time to treatment failure was 15 weeks. Serious drops in blood counts were common, including severe low platelet counts, with 3 bleeding cases. Survival seemed significantly associated with performance status, a measure of everyday functioning. The authors concluded the regimens could control symptoms and disease progression with a modest toxicity profile. They said this small series needs confirming in a larger prospective trial, and noted their symptom scale had not been prospectively validated.

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: Retrospective analysis of a single-institution case series of patients given second- or third-line chemotherapy
• Who was studied: 17 patients with relapsed malignant pleural mesothelioma (12 males, 5 females; median age 61, range 47–74) seen at a Padua, Italy, cancer centre since 2006. 13 received the regimen as second-line treatment and 4 as third-line treatment.
• Exposure: No asbestos exposure was studied. The studied treatment was gemcitabine 1000 mg/m2 on days 1 and 8, combined with the platinum drug not used in first-line treatment (cisplatin 75 mg/m2 or carboplatin AUC 5 on day 1), every 3 weeks for 3–6 cycles.
• Main results:
  • Among the 15 evaluable patients there was no partial response. 10 (67%; 95% CI 38–88%) had stable disease and 5 (33%; 95% CI 12–62%) had progressive disease.
  • No partial responses were seen.
  • Symptoms improved in 8 of the evaluable patients (53%; 95% CI 26–79%), which was 47% of the intent-to-treat population.
  • In the intent-to-treat population (all 17 patients), median survival was 28 weeks (range 13–168) and median time to treatment failure was 15 weeks (range 3–75).
  • Thrombocytopenia (low platelet count) by patient, among evaluable patients: 2 (13%) grade 4 and 6 (40%) grade 3. Also among evaluable patients: grade 3 leucopenia 4 (27%), grade 3 anaemia 3 (20%) and grade 3 neutropenia 6 (40%).
  • Among patients with grade 3 to 4 thrombocytopenia there were 3 cases of bleeding. Febrile neutropenia occurred in 1 patient.
  • Grade 3 non-blood side effects in evaluable patients were nausea (14%), vomiting (7%) and asthenia (21%). There were no grade 4 non-blood side effects.
  • None of the variables analysed (performance status, histology, age, response, time to progression after first-line treatment) influenced time to treatment failure. Overall survival seemed to be significantly associated with ECOG performance status (p = 0.026).
• The authors' conclusion: The authors concluded that gemcitabine-platinum regimens are able to control symptoms and disease progression with a modest toxicity profile, and that the results should be confirmed in a larger prospective trial.
• Limitations the authors state:
  • The results come from a small series of patients and need confirmation in a prospective trial in a larger cohort.
  • The symptom scale used to define clinical benefit had not been prospectively validated.

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, Pleural Mesothelioma, Pemetrexed (Alimta), Gemcitabine, Cisplatin, Carboplatin, Neoadjuvant Chemotherapy, Pleurectomy/Decortication (P/D).

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