Gemcitabine combined with oxaliplatin in pretreated patients with malignant pleural mesothelioma: an observational study

Our plain-English summary of Gemcitabine combined with oxaliplatin in pretreated patients with malignant pleural mesothelioma: an observational study, by A. Xanthopoulos, T.T. Bauer, T.G. Blum, et al (Journal of Occupational Medicine and Toxicology, 2008).

The study

• Authors: A. Xanthopoulos, T.T. Bauer, T.G. Blum, J. Kollmeier, N. Schönfeld, M. Serke
• Journal: Journal of Occupational Medicine and Toxicology
• Published: 2008;3:34
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: The aim of this study was to investigate the efficacy and safety of oxaliplatin +/- gemcitabine in patients with diffuse malignant pleural mesothelioma (MPM) pretreated with pemetrexed.

Methods: The study enrolled consecutive patients with relapsed MPM, all of them pretreated with a platin-pemetrexed-based chemotherapy. Oxaliplatin 80 mg/m2 was administered as monotherapy or in combination with gemcitabine 1000 mg/m2 given on day 1 and 8. Cycles were repeated every 21 days. The primary endpoints were response rate and disease control rate. Secondary endpoints included overall survival (OS), time to tumour progression (TTP), progression-free survival (PFS), time to treatment failure (TTF), and toxicity.

Results: Between February 2005 and September 2007 29 patients (median age: 65.0 years, World Health Organisation (WHO) performance status: 0-3) were enrolled. The follow-up period encompassed 5.4 to 97.4 weeks (median: 24.3 weeks). Out of these 29 patients, 15 were treated in second, 10 in third, 3 in fourth and 1 in fifth line, respectively. The majority of the patients received the combination oxaliplatin and gemcitabine (n = 25 vs. 4; 86.2 vs. 13.8%).The median overall survival (OS) was 71.7 weeks (30.6-243.3 weeks), whereas survival from the start of oxaliplatin/gemcitabine-treatment was 24.3 weeks (5.4-97.3 weeks). Median time to tumour progression (TTP) was 9.3 weeks (3.0-67.6 weeks).Partial response (PR) was observed in 2 patients (6.9%), stable disease (SD) for at least three courses of treatment in 11 patients (37.9%). Thus, disease control rate was 44.8%, whereas 16 of 29 patients exhibited progressive disease (55.2%).The toxicity profile was favourable, with no WHO grade 4-toxicities, only few dose-reductions were performed due to non-symptomatic haematotoxicities (neutropenia, thrombopenia). Mild WHO grade 2 neurotoxicity was seen in 6 patients.

Conclusion: Pemetrexed-pretreated patients with progressive MPM may benefit from a consecutive chemotherapy with oxaliplatin and gemcitabine without significant toxicity.

In plain English

This observational study, from a lung-disease clinic in Berlin, Germany, followed 29 consecutive patients with malignant pleural mesothelioma whose disease had progressed after chemotherapy combining a platinum drug with pemetrexed. Between February 2005 and September 2007, 25 patients received oxaliplatin with gemcitabine and 4 received oxaliplatin alone. The study was about treatment, not causes. Asbestos exposure was recorded as yes for 17 patients, no for 1, and not defined for 11. A partial response (partial tumor shrinkage) was seen in 2 of the 29 patients (6.9%). The disease stayed stable for at least three treatment courses in 11 (37.9%), giving a disease control rate of 44.8%, while 16 patients (55.2%) had progressive disease. Median survival from the start of this treatment was 24.3 weeks, and median time to tumor progression was 9.3 weeks. No WHO grade 4 side effects were reported, and 6 patients had mild grade 2 nerve side effects. The authors concluded that such patients may benefit from oxaliplatin and gemcitabine without significant toxicity. They noted limits from the observational design, the mixed patient group, and difficulty comparing with other studies.

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: Observational study of consecutive patients treated at one clinic, with no comparison group
• Who was studied: 29 consecutive patients (27 male) with relapsed malignant pleural mesothelioma, all previously treated with platinum/pemetrexed chemotherapy, at the Respiratory Diseases Clinic Heckeshorn, Berlin, Germany, enrolled February 2005 to September 2007; median age 65.0 years; 27 epithelial, 1 sarcomatoid, 1 biphasic
• Exposure: The study assessed chemotherapy, not asbestos exposure: oxaliplatin 80 mg/m2 with or without gemcitabine 1000 mg/m2 on days 1 and 8 of 21-day cycles. Asbestos exposure was recorded as yes in 17 (58.6%), no in 1 (3.4%) and not defined in 11 (37.9%). No fiber types or jobs were reported.
• Main results:
  • 25 patients received oxaliplatin plus gemcitabine and 4 received oxaliplatin alone (86.2 vs. 13.8%)
  • Partial response in 2 of 29 patients (6.9%)
  • Stable disease for at least three courses of treatment in 11 patients (37.9%)
  • Disease control rate 44.8%; 16 of 29 patients (55.2%) had progressive disease
  • Median overall survival from diagnosis of mesothelioma was 71.7 weeks (range 30.6 to 243.3 weeks)
  • Median survival from the start of oxaliplatin with or without gemcitabine was 24.3 weeks (range 5.4 to 97.3 weeks)
  • Median time to tumor progression was 9.3 weeks (range 3.0 to 67.6 weeks)
  • Progression-free survival and time to treatment failure were both 11.7 weeks (range 3.0 to 50.4 weeks)
  • No WHO grade 4 toxicities. There were 14 episodes of WHO grade 2 to 3 neutropenia in 10 patients and 10 episodes of grade 2 to 3 thrombocytopenia in 10 patients, all rapidly reversible.
  • Mild WHO grade 2 neurotoxicity in 6 patients (20.7%); renal toxicity in 1 patient (3.4%)
• The authors' conclusion: The authors concluded that pemetrexed-pretreated patients with progressive malignant pleural mesothelioma may benefit from subsequent chemotherapy with oxaliplatin and gemcitabine without significant toxicity, and that it can be seen as an option until randomized trial data are available.
• Limitations the authors state:
  • Observational design
  • The patients included were a mixed (heterogeneous) group
  • Patients were included at any stage of the disease (second to fifth line of treatment), which may reduce how well the efficacy results apply to second-line therapy
  • Comparison with other second-line studies is difficult because patient characteristics, regimens, response evaluation and timing vary widely

Topics

Medical terms in this study, explained in our Lexicon: Gemcitabine, Pleural Mesothelioma, Pemetrexed (Alimta), Chemotherapy, Overall Survival, Progression-Free Survival, Performance Status, Median Overall Survival.

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• The predictive role of serum VEGF in an advanced malignant mesothelioma patient cohort treated with thalidomide alone or combined with cisplatin/gemcitabine — S.C. Kao, R. Harvie, et al. (2012)
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• Final results of DIADEM, a phase II study to investigate the efficacy and safety of durvalumab in advanced pretreated malignant pleural mesothelioma — S. Canova, G.L. Ceresoli, et al. (2022)

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