Third-line chemotherapy with carboplatin, gemcitabine and liposomised doxorubicin for malignant pleural mesothelioma

Our plain-English summary of Third-line chemotherapy with carboplatin, gemcitabine and liposomised doxorubicin for malignant pleural mesothelioma, by V.A. de Lima, J.B. Sørensen (Medical Oncology, 2015).

The study

• Authors: V.A. de Lima, J.B. Sørensen
• Journal: Medical Oncology
• Published: 2015;32(2):458
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

There is no well-defined standard third-line chemotherapy for advanced malignant pleural mesothelioma (MPM). However, combination of carboplatin, liposomised doxorubicin (Caelyx) and gemcitabine (CCG regimen) has revealed noteworthy activity when used as first-line treatment. The aim of this study is to assess efficacy and toxicity profile for patients with MPM receiving CCG regimen as a third-line treatment. Carboplatin (AUC 5), Caelyx (30 mg/m(2)) and Gemcitabine (1,000 mg/m(2)) day 1, together with Gemcitabine (800 mg/m(2)) day 8, were given in up to six cycles. Patients were unresectable, PS 0-2, and had previously received a first-line platinum-based regimen and either vinorelbine or pemetrexed as second line. Response to treatment was assessed by CT scan using Modified RECIST criteria for mesothelioma. Forty-three patients were treated between 2010 and 2014. Median age was 67 years (47-82), 72 % males, and 79 % had previous asbestos exposure. Ninety per cent had PS 0-1, 58 % had epitheloid subtype and 63 % IMIG stage IV. First-line treatment was platinum and pemetrexed in 42 cases. Second-line treatment was vinorelbine in 42 cases and pemetrexed in one patient. Median lead time from cessation of second-line treatment to start of third CCG was 1 month. Twenty-eight per cent of the patients received six cycles, while treatment was postponed due to toxicities, mainly haematological, in 56 % of cases. No toxicity-related deaths occurred. Partial response (PR) occurred in 14 %, and disease control rate (DCR) was 60 %. Medians of overall survival (OS) from diagnosis and from start of CCG treatment were 25.2 months (18.4-31.5 months) and 6.8 months (5.4-8.4 months), respectively. Progression-free survival (PFS) was 4.1 months (1.7-4.5 months). Third-line CCG revealed a noteworthy efficacy with a DCR of 60.4 %. It was, however, associated with considerable haematological toxicity. Less toxic and more active treatment options are clearly needed.

In plain English

This was a retrospective analysis, on behalf of the Danish Mesothelioma Group, of 43 patients with malignant pleural mesothelioma that could not be removed surgically. They were treated at Rigshospitalet in Copenhagen from August 2010 to January 2014. All had already received two earlier lines of chemotherapy. As third-line treatment they received carboplatin, gemcitabine and liposomised doxorubicin (Caelyx), the CCG regimen, for up to six cycles. Thirty-four of the 43 patients (79.1%) had previous asbestos exposure. Six patients (13.9%) had a partial response and 20 (46.5%) had no change, a disease control rate of 60.4%. Median overall survival was 25.2 months from diagnosis (95% confidence interval 18.45 to 31.94) and 6.9 months from the start of CCG (5.46 to 8.46). Median progression-free survival from the start of CCG was 4.1 months (95% confidence interval 2.34 to 5.92). Side effects were mainly in the blood: up to 33% had grade 4 neutropenia, 56% had anaemia needing transfusion, and ten patients were hospitalised with febrile neutropenia. No treatment-related deaths occurred. The authors concluded that the activity was limited and that treatments with better efficacy and less toxicity are needed.

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 patient records (single centre, national referral centre) of a third-line chemotherapy regimen
• Who was studied: 43 patients with histologically verified, nonresectable malignant pleural mesothelioma treated at the Finsen Centre, Rigshospitalet/Copenhagen University Hospital, Denmark, August 2010 to January 2014. All had previously received platinum-based first-line chemotherapy and second-line vinorelbine (42 patients) or pemetrexed (1 patient). Median age was 67.2 years, 31 (72%) were men, and 34 (79.1%) had previous asbestos exposure (6 not exposed, 3 unknown).
• Exposure: The treatment studied was the CCG regimen: carboplatin AUC 5, Caelyx 30 mg/m2 and gemcitabine 1,000 mg/m2 on day 1, plus gemcitabine 800 mg/m2 on day 8, for a maximum of six cycles. Doses were automatically reduced from cycle 4. Asbestos exposure was recorded as a patient characteristic only; no fiber types were given.
• Main results:
  • Best response to third-line CCG among the 43 patients: partial response in 6 patients (13.9%), no change in 20 patients (46.5%), and a disease control rate of 60.4%.
  • Median overall survival from diagnosis was 25.2 months (95% CI 18.45 to 31.94).
  • From the start of CCG, median overall survival was 6.9 months (95% CI 5.46 to 8.46) and progression-free survival was 4.1 months (95% CI 2.34 to 5.92).
  • Patients who had a partial or complete response to first-line treatment had a median overall survival from the start of third-line treatment of 7.83 months, versus 5.2 months for those with progression or no change (p = 0.003).
  • Patients in stage I to II survived longer than those in stage III and IV (13.3 vs 6.8 months; p = 0.02).
  • Overall survival was somewhat longer for women than for men, but the difference was not statistically significant (31.6 vs 25.1 months, p = 0.59).
  • Toxicity was mainly haematological. Treatment was postponed for 1 week or more in 27 cases. Up to 33% of patients had grade 4 neutropenia, 56% had anaemia requiring transfusion, and 10 patients (23.2%) were hospitalised for febrile neutropenia.
  • No treatment-related deaths occurred.
• The authors' conclusion: The authors concluded that CCG had some efficacy as third-line treatment, with a disease control rate of 60%, but objective responses were rare and haematological toxicity was the main problem. They judged the activity to be limited and said treatment with better efficacy and less toxicity is needed.
• Limitations the authors state:
  • Few studies have examined third-line chemotherapy in this disease, so there are few sources against which to compare the results.
  • Comparison between studies is hampered by differences in drugs, treatment line, patient selection, and statistical variation due to the relatively small patient populations.

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, Carboplatin, Gemcitabine, Doxorubicin, Pleural Mesothelioma, Unresectable, Vinorelbine, Pemetrexed (Alimta).

Related studies

• Treatment of malignant pleural mesothelioma with carboplatin, liposomized doxorubicin, and gemcitabine: a phase II study — G. Hillerdal, J.B. Sorensen, et al. (2008)
• Successful salvage chemotherapy with gemcitabine and vinorelbine in a malignant pleural mesothelioma patient previously treated with pemetrexed — T. Agatsuma, T. Koizumi, et al. (2010)
• Vinorelbine and gemcitabine as second- or third-line therapy for malignant pleural mesothelioma — M.G. Zauderer, S.L. Kass, et al. (2014)
• 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)
• A phase II study of the combination of gemcitabine and imatinib mesylate in pemetrexed-pretreated patients with malignant pleural mesothelioma — P.A. Zucali, M. Perrino, et al. (2020)
• 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)

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