Pemetrexed plus carboplatin in elderly patients with malignant pleural mesothelioma: combined analysis of two phase II trials

Our plain-English summary of Pemetrexed plus carboplatin in elderly patients with malignant pleural mesothelioma: combined analysis of two phase II trials, by G.L. Ceresoli, B. Castagneto, P.A. Zucali, et al (British Journal of Cancer, 2008).

The study

• Authors: G.L. Ceresoli, B. Castagneto, P.A. Zucali, A. Favaretto, M. Mencoboni, F. Grossi, D. Cortinovis, G. Del Conte, A. Ceribelli, A. Bearz, S. Salamina, F. De Vincenzo, F. Cappuzzo, M. Marangolo, V. Torri, A. Santoro
• Journal: British Journal of Cancer
• Published: 2008;99(1):51-6
• Cited by: 76 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The incidence of malignant pleural mesothelioma (MPM) in elderly patients is increasing. In this study, pooled data from two phase II trials of pemetrexed and carboplatin (PC) as first-line therapy were retrospectively analysed for comparisons between age groups. Patients received pemetrexed 500 mg m(-2) and carboplatin AUC 5 mg ml(-1) min(-1) intravenously every 21 days with standard vitamin supplementation. Elderly patients were defined as those >or=70 years old. A total of 178 patients with an ECOG performance status of <or=2 were included. Median age was 65 years (range 38-79), with 48 patients >or=70 years (27%). Grade 3-4 haematological toxicity was slightly worse in >or=70 vs <70-year-old patients, with neutropenia observed in 25.0 vs 13.8% (P=0.11), anaemia in 20.8 vs 6.9% (P=0.01) and thrombocytopenia in 14.6 vs 8.5% (P=0.26). Non-haematological toxicity was mild and similar in the two groups. No significant difference was observed in terms of overall disease control (60.4 vs 66.9%, P=0.47), time to progression (7.2 vs 7.5 months, P=0.42) and survival (10.7 vs 13.9 months, P=0.12). Apart from slightly worse haematological toxicity, there was no significant difference in outcome or toxicity between age groups. The PC regimen is effective and well tolerated in selected elderly patients with MPM.

In plain English

This study pooled the individual patient data from two earlier phase II trials run at Italian centres and re-analysed them retrospectively to compare older and younger patients. All 178 patients had malignant pleural mesothelioma, had not had chemotherapy before, and were not candidates for surgery. All received pemetrexed plus carboplatin every 21 days. Forty-eight patients were aged 70 or older and 130 were younger. The tumour response rate was 14.6% in the older group and 23.8% in the younger group, a difference that was not statistically significant. Median time to disease progression was 7.2 versus 7.5 months. Median overall survival was 10.7 versus 13.9 months, also not statistically significant. Severe anaemia was significantly more common in the older patients (20.8% versus 6.9%). Severe neutropenia was more frequent in the older patients (25.0% versus 13.8%), but that difference was not significant. No treatment-related deaths occurred. The authors concluded that the regimen is effective and safe in elderly patients with good performance status. They also noted that only 11 patients were 75 or older and that data on other illnesses were not available. The study concerned treatment, not asbestos exposure.

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 pooled analysis of individual patient data from two prospective phase II chemotherapy trials, comparing patients aged 70 or older with patients under 70
• Who was studied: 178 patients with histologically proven malignant pleural mesothelioma who had not had chemotherapy and were not surgical candidates. They were enrolled at eight Italian institutions (trial A, 102 patients) and three other Italian centres (trial B, 76 patients) between November 2002 and July 2005. 48 were aged 70 or older and 130 were under 70. Median age was 65 (range 38 to 79). Follow-up ran to March 2008.
• Exposure: No asbestos exposure was studied. The study examined chemotherapy: pemetrexed 500 mg per square metre followed by carboplatin at AUC 5, both given intravenously on day 1 every 21 days, with vitamin supplementation.
• Main results:
  • Among patients aged 70 or older, 7 had a partial response, for an objective response rate of 14.6% (95% CI 6.1 to 27.8%).
  • Among patients under 70 the response rate was 23.8% (95% CI 16.8 to 32.1%). The difference between age groups was not statistically significant (P = 0.15).
  • Overall disease control was 60.4% in patients aged 70 or older and 66.9% in younger patients, not significantly different (P = 0.47).
  • Median time to progression was 7.2 months for patients aged 70 or older and 7.5 months for those under 70 (P = 0.42).
  • Median overall survival was 13.9 months in patients under 70 and 10.7 months in those aged 70 or older. The difference was not statistically significant (P = 0.12).
  • Estimated survival at 6 months and 1 year was 69% and 48% for patients aged 70 or older, and 76% and 55% for those under 70.
  • Severe (grade 3 to 4) anaemia was significantly more frequent in patients aged 70 or older: 20.8% versus 6.9% (P = 0.01).
  • Grade 3 to 4 neutropenia occurred in 25.0% of patients aged 70 or older versus 13.8% of younger patients (P = 0.11). Febrile neutropenia occurred in 2.1% versus 3.8%.
  • Grade 3 to 4 thrombocytopenia occurred in 14.6% of patients aged 70 or older versus 8.5% of younger patients (P = 0.26).
  • Non-haematological toxicity was mild and similar in both age groups, and there were no treatment-related deaths in either group.
• The authors' conclusion: The authors concluded that their data suggest pemetrexed plus carboplatin is effective and safe in elderly patients with malignant pleural mesothelioma who have good performance status. They said extra caution is needed for patients aged 75 or older and that prospective trials in elderly patients are warranted.
• Limitations the authors state:
  • Data on co-morbidity were not available, raising the possibility that only fit elderly patients were included (selection bias).
  • Only 11 patients were aged 75 or older, so the results should be regarded with caution for the oldest patients.
  • The two trials used different response criteria, and response classification was not reviewed centrally.
  • No second-line therapy was planned, which may have influenced the overall survival data.

Topics

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

Medical terms in this study, explained in our Lexicon: Pemetrexed (Alimta), Carboplatin, Pleural Mesothelioma, First-line Therapy, ECOG Performance Status, Neutropenia.

Related studies

• Phase II study of pemetrexed and carboplatin plus bevacizumab as first-line therapy in malignant pleural mesothelioma — G.L. Ceresoli, P.A. Zucali, et al. (2013)
• Preclinical emergence of vandetanib as a potent antitumour agent in mesothelioma: molecular mechanisms underlying its synergistic interaction with pemetrexed and carboplatin — E. Giovannetti, P.A. Zucali, 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)
• Sunitinib combined with pemetrexed and carboplatin in patients with advanced solid malignancies--results of a phase I dose-escalation study — N. Blais, D.R. Camidge, et al. (2013)
• Tumour Treating Fields in combination with pemetrexed and cisplatin or carboplatin as first-line treatment for unresectable malignant pleural mesothelioma (STELLAR): a multicentre, single-arm phase 2 trial — G.L. Ceresoli, J.G. Aerts, et al. (2019)
• The role of pemetrexed combined with targeted agents for non-small cell lung cancer — K. Konopa, J. Jassem (2010)

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