Multicentre phase II study of gemcitabine and cisplatin in malignant pleural mesothelioma

Our plain-English summary of Multicentre phase II study of gemcitabine and cisplatin in malignant pleural mesothelioma, by J.M. van Haarst, P. Baas, C.H. Manegold, et al (British Journal of Cancer, 2002).

The study

• Authors: J.M. van Haarst, P. Baas, C.H. Manegold, J.H. Schouwink, J.A. Burgers, H.G. de Bruin, W.J. Mooi, R.J. van Klaveren, M.J. de Jonge, J.P. van Meerbeeck
• Journal: British Journal of Cancer
• Published: 2002;86(3):342-5
• Cited by: 105 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Unlabelled: Malignant pleural mesothelioma is a notoriously chemoresistant tumour. However, a recent single institution study showed an impressive activity of gemcitabine and cisplatin. Our aim is to investigate the efficacy and toxicity of a gemcitabine and cisplatin combination in selected and chemo-naive patients with histologically proven malignant pleural mesothelioma.

Method: Gemcitabine 1250 mg m(-2) was administered on day 1 and day 8 and cisplatin 80 mg m(-2) was administered on day 1 in a 3-week cycle with a maximum of six cycles. Response and toxicity evaluations were performed according to WHO and NCIC-CTC criteria. Pathology and radiology were centrally reviewed. Results show that in 25 evaluable patients, four PR were observed (ORR 16%, 95% CI 1-31%). Responses of seven patients were unevaluable. No unexpected toxicity occurred. Time to progression was 6 months (5-7 months) with a median survival from registration of 9.6 months (95% CI 8-12 months). In conclusion this trial excludes with 90% power a response rate of greater than 30% in patients with malignant pleural mesothelioma using a combination of gemcitabine and cisplatin at the proposed dose and schedule.

Copyright 2002 The Cancer Research Campaign

In plain English

This phase II confirmation trial, at four institutes in the Netherlands and Germany, tested gemcitabine plus cisplatin in patients with malignant pleural mesothelioma and no prior chemotherapy. From April to December 1999, 32 eligible patients received gemcitabine on days 1 and 8 and cisplatin on day 1 of 21-day cycles, up to six cycles. Asbestos exposure was not examined. Of 25 response-evaluable patients, four had a partial response (16%, 95% confidence interval 1 to 31%); seven others were unevaluable. Median survival from the start of treatment was 9.4 months (95% confidence interval 7.3 to 11.4) in the 32 eligible patients; median time to progression was 6.1 months (95% confidence interval 5.7 to 6.5) in the 25 evaluable patients. Drug-related side effects were the main reason six patients stopped chemotherapy. Questionnaires from 19 and 18 of the 25 evaluable patients, after one and two cycles, showed less pain than at baseline. The authors concluded the trial excludes, with 90% power, a response rate above 30% at this dose and schedule; they could not recommend it as standard therapy.

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 phase II clinical trial (single-arm, Simon two-stage design) of chemotherapy
• Who was studied: 32 eligible patients with histologically confirmed malignant pleural mesothelioma and no prior chemotherapy, enrolled April to December 1999 at four institutes in the Netherlands and Germany; 25 were evaluable for response
• Exposure: No asbestos exposure was studied. The treatment was gemcitabine 1250 mg per square metre on days 1 and 8 plus cisplatin 80 mg per square metre on day 1 of each 21-day cycle, for up to six cycles
• Main results:
  • Among the 25 evaluable patients, four had a partial response (response rate 16%, 95% CI 1 to 31%)
  • Seven of the 32 eligible patients could not be evaluated for response (lost to follow-up, death, toxicity, refusal or rapid deterioration)
  • Median survival from the start of treatment for the 32 eligible patients was 9.4 months (95% CI 7.3 to 11.4 months); median survival from diagnosis was 14.6 months (95% CI 12.7 to 16.4 months)
  • Median time to progression in the 25 evaluable patients was 6.1 months (95% CI 5.7 to 6.5 months)
  • In six patients, drug-related toxicity was the main reason chemotherapy was stopped (four of them because of grade 3 to 4 nausea and vomiting)
  • Quality-of-life data came from 19 (76%) and 18 (72%) of the 25 evaluable patients after one and two cycles. Compared with baseline, these patients reported less pain. The authors reported no significant change in other symptoms or quality-of-life items.
  • When patients from one centre were re-evaluated with unidimensional criteria like those of the earlier study, one of seven patients with stable disease became an additional confirmed partial response
• The authors' conclusion: The authors concluded that the trial excludes, with 90% power, a response rate greater than 30% for gemcitabine plus cisplatin at this dose and schedule. They also concluded that they cannot recommend the combination as standard therapy for malignant pleural mesothelioma.
• Limitations the authors state:
  • Compliance with quality-of-life scoring beyond two cycles was below 50%, so symptoms and quality of life after two cycles could not be reliably estimated
  • The authors noted that the value of measuring quality of life in a phase II trial can be disputed
  • The improvement in pain might reflect more intensive pain medication rather than the chemotherapy itself

Topics

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

Medical terms in this study, explained in our Lexicon: Gemcitabine, Cisplatin, Pleural Mesothelioma, Pathology, Median Overall Survival.

Related studies

• A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma — A.K. Nowak, M.J. Byrne, et al. (2002)
• 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)
• 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)
• 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)
• 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)
• 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)

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