A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma

Our plain-English summary of A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma, by A.K. Nowak, M.J. Byrne, R. Williamson, et al (British Journal of Cancer, 2002).

The study

• Authors: A.K. Nowak, M.J. Byrne, R. Williamson, G. Ryan, A. Segal, D. Fielding, P. Mitchell, A.W. Musk, B.W. Robinson
• Journal: British Journal of Cancer
• Published: 2002;87(5):491-6
• Cited by: 150 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Our previous phase II study of cisplatin and gemcitabine in malignant mesothelioma showed a 47.6% (95% CI 26.2-69.0%) response rate with symptom improvement in responding patients. Here we confirm these findings in a multicentre setting, and assess the effect of this treatment on quality of life and pulmonary function. Fifty-three patients with pleural malignant mesothelioma received cisplatin 100 mg m(-2) i.v. day 1 and gemcitabine 1000 mg m(-2) i.v. days 1, 8, and 15 of a 28 day cycle for a maximum of six cycles. Quality of life and pulmonary function were assessed at each cycle. The best response achieved in 52 assessable patients was: partial response, 17 (33%, 95% CI 20-46%); stable disease, 31 (60%); and progressive disease, four (8%). The median time to disease progression was 6.4 months, median survival from start of treatment 11.2 months, and median survival from diagnosis 17.3 months. Vital capacity and global quality of life remained stable in all patients and improved significantly in responding patients. Major toxicities were haematological, limiting the mean relative dose intensity of gemcitabine to 75%. This schedule of cisplatin and gemcitabine is active in malignant mesothelioma in a multicentre setting. Investigation of alternative scheduling is needed to decrease haematological toxicity and increase the relative dose intensity of gemcitabine whilst maintaining response rate and quality of life.

In plain English

This was a phase II treatment trial, not a study of asbestos exposure. At six Australian referral centres, patients with pleural malignant mesothelioma received cisplatin and gemcitabine in 28-day cycles, up to six cycles, with no untreated comparison group. Of 55 patients entered, 53 were eligible. Of 52 whose response could be assessed, none had a complete response, 17 (33%, 95% confidence interval 20 to 46%) had a partial response, 31 (60%) had stable disease and four had progressive disease. Median time to progression was 6.4 months and median survival from start of treatment 11.2 months. Lung capacity and overall quality of life did not change significantly in the whole group but improved in patients who responded. The main side effects were low blood counts, which limited the gemcitabine dose delivered. The authors concluded the regimen produced responses in a third of patients, and stated that only a randomised trial could show whether it improves survival.

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: multicentre, single-arm phase II chemotherapy trial using a one-sample multiple testing design, with no untreated control group
• Who was studied: Patients with malignant pleural mesothelioma from six tertiary referral centres across Australia. 55 were entered, 53 were eligible (45 men, 8 women; median age 63, range 47 to 76), and 52 could be assessed for response. Study dates are not given.
• Exposure: No asbestos exposure was studied or reported. The intervention was chemotherapy: cisplatin 100 mg per square metre intravenously on day 1 and gemcitabine 1000 mg per square metre on days 1, 8 and 15, repeated every 28 days for up to six cycles.
• Main results:
  • No patient had a complete response.
  • Among assessable patients, 17 (33%) had a partial response and 31 (60%) had stable disease as their best response.
  • Four patients (7%) had progressive disease without any period of stabilisation.
  • The overall response rate was 33% (95% CI 20 to 46%).
  • Median time to progression was 6.4 months.
  • Median survival from start of treatment was 11.2 months.
  • Median survival from diagnosis was 17.3 months for all patients.
  • Responders had a median survival from start of treatment of 12.2 months compared with 9.1 months for non-responders. The difference was not statistically significant.
  • In the whole group there was no significant change in vital capacity (FVC) from baseline.
  • FVC differed significantly between responders and non-responders (P=0.002), with FVC improving in patients who had a partial response.
  • Responders had a significant improvement in global quality of life compared with non-responders over six cycles of chemotherapy (P=0.006 in the text).
  • In the group as a whole there was no significant change in global quality of life from baseline.
  • Fatigue was the only symptom scale that worsened from baseline in the group as a whole.
  • Grade 3 or 4 thrombocytopenia (low platelets) occurred in 49% of patients and grade 3 or 4 neutropenia (low white cells) in 56%.
  • Two patients (4%) developed febrile neutropenia.
  • There were no treatment-related deaths.
  • The relative dose intensity of gemcitabine actually delivered was lower than planned (median 72%, mean 75%).
• The authors' conclusion: The authors concluded that this dose and schedule of cisplatin and gemcitabine produced objective responses in a third of treated patients in a multicentre setting, with improved global quality of life and respiratory function in responders.
• Limitations the authors state:
  • The requirements for measurable disease and a life expectancy of over 12 weeks may have selected patients with more slowly progressing disease, which may have influenced the survival figures.
  • Whether the regimen improves survival can only be answered by a randomised controlled trial.
  • Without an untreated control group it is difficult to judge whether the regimen benefits quality of life.
  • There were too few patients with biphasic and sarcomatoid tumours for a subgroup analysis.
  • The lung cancer quality-of-life module used may not suit the symptoms of malignant mesothelioma.

Topics

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

Medical terms in this study, explained in our Lexicon: Cisplatin, Gemcitabine, Mesothelioma, Quality of Life, Disease Progression, Median Overall Survival.

Related studies

• Multicentre phase II study of gemcitabine and cisplatin in malignant pleural mesothelioma — J.M. van Haarst, P. Baas, et al. (2002)
• A phase II trial of low-dose gemcitabine in a prolonged infusion and cisplatin for malignant pleural mesothelioma — V. Kovac, M. Zwitter, et al. (2012)
• A phase II trial of prolonged, continuous infusion of low-dose gemcitabine plus cisplatin in patients with advanced malignant pleural mesothelioma — O. Arrieta, D. López-Macías, et al. (2014)
• Epirubicin and gemcitabine as first-line treatment in malignant pleural mesothelioma — L. Portalone, A. Antilli, et al. (2005)
• 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)
• 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)

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