Phase II trial of carboplatin in the management of malignant mesothelioma

Our plain-English summary of Phase II trial of carboplatin in the management of malignant mesothelioma, by D. Raghavan, P. Gianoutsos, J. Bishop, et al (Journal of Clinical Oncology, 1990).

The study

• Authors: D. Raghavan, P. Gianoutsos, J. Bishop, J. Lee, I. Young, P. Corte, P. Bye, B. McCaughan
• Journal: Journal of Clinical Oncology
• Published: 1990;8(1):151-4
• Cited by: 62 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Thirty-one patients with advanced malignant mesothelioma, previously untreated or having received only one prior cytotoxic regimen, were treated in a prospective, single-arm phase II trial with carboplatin (NSC 241240) at a dose of 150 mg/m2 per day intravenously (IV) for 3 days (450 mg/m2/course). One complete remission and four partial remissions were achieved, yielding an overall objective response rate of 16% (95% confidence interval [CI], 5.4% to 34%). The median duration of remission was 8 months (range, 5 to 17). Nonhematological toxicity was mild (only 12% with World Health Organization [WHO] grade 3 vomiting); 16% suffered WHO grade 3 to 4 hematological toxicity, but there were no life-threatening episodes and no treatment-related deaths. Carboplatin has modest activity against malignant mesothelioma and, because of its low toxicity, has a role in the management of this disease.

In plain English

This was a phase II trial in Australia testing the chemotherapy drug carboplatin in 31 patients with advanced malignant mesothelioma. They were treated between September 1985 and December 1988 at hospitals in Sydney and Melbourne. Patients had received no prior chemotherapy or only one prior regimen. Most had disease in the pleura (the lining of the chest), and two had peritoneal mesothelioma. Asbestos exposure was recorded as yes for 19 patients, no for 5 and unknown for 7. Patients received carboplatin into a vein for 3 days, repeated every 28 days. One patient had a complete remission and four had partial remissions, an objective response rate of 16% (95% confidence interval 5.4% to 34%). Remissions lasted a median of 8 months, and median survival for all patients was 8 months. Four patients (12%) had severe gastrointestinal side effects. Lowered blood counts were the dose-limiting side effect, but there were no life-threatening infections and no treatment-related deaths. The authors concluded that carboplatin has modest activity against malignant mesothelioma and, because of its low toxicity, has a role in managing the disease. They described the trial as small.

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: Prospective, single-arm phase II trial of carboplatin (a chemotherapy drug)
• Who was studied: 31 patients (28 male, 3 female; median age 59, range 33 to 74) with biopsy-proven advanced malignant mesothelioma, previously untreated or given only one prior chemotherapy regimen. They were treated September 1985 to December 1988 at Royal Prince Alfred Hospital, Sydney, and Peter MacCallum Cancer Institute, Melbourne, Australia. Tumor was in the pleura in 28; two patients had peritoneal mesothelioma.
• Exposure: The study tested a treatment, not an asbestos exposure: carboplatin 150 mg/m2 per day into a vein for 3 days (450 mg/m2 per course), repeated every 28 days. Patient asbestos exposure was recorded as yes 19, no 5, unknown 7. No fiber types were reported.
• Main results:
  • Among the 31 patients, 1 had a complete remission and 4 had partial remissions, an objective response rate of 16% (95% CI, 5.4% to 34%). 8 had stable disease and 18 had progressive disease.
  • Among the 5 responders, the median duration of remission was 8 months (range, 5 to 17 months).
  • Responses were seen in pleural disease in 4 patients, in a lymph node mass in 1, in a chest wall mass in 1, and in malignant ascites in 1 of the 2 patients with peritoneal mesothelioma.
  • Median survival was 21 months (range, 11 to 24+ months) for responders and 7 months (range, 2 to 17 months) for nonresponders reassessed after two courses. Median total survival was 8 months. The authors said they could not assess whether the longer survival of responders was due to treatment, patient selection or disease characteristics.
  • 11 patients (35%) lived 12 months or longer from the start of carboplatin.
  • 4 patients (12%) had severe gastrointestinal side effects. The dose-limiting toxicity was suppression of blood counts: 2 patients had grade 4 thrombocytopenia (low platelets) and 2 patients (6%) had grade 3 leukopenia (low white cells). There were no life-threatening infections and no toxic deaths.
  • Of 5 patients previously treated with anthracyclines, 1 had a partial response to carboplatin, lasting 5 months. The 3 responders re-treated with carboplatin at relapse did not respond again.
• The authors' conclusion: The authors concluded that carboplatin has modest activity against malignant mesothelioma and, because of its low toxicity, has a role in managing the disease. They had begun studies of carboplatin in combination regimens.
• Limitations the authors state:
  • The patient numbers were small, and the authors did not attempt to define factors predicting response or survival.
  • No response rate was calculated for previously treated patients or for peritoneal versus pleural disease.
  • The study was not designed to assess survival as a major end point.
  • The data do not allow a direct comparison of carboplatin with doxorubicin.

Topics

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

Medical terms in this study, explained in our Lexicon: Carboplatin, Mesothelioma, confidence interval.

Related studies

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• 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)
• Randomised phase II study of cisplatin-etoposide versus infusional carboplatin in advanced non-small-cell lung cancer and mesothelioma — S.C. White, H. Anderson, et al. (2000)
• Treatment of malignant pleural mesothelioma with carboplatin, liposomized doxorubicin, and gemcitabine: a phase II study — G. Hillerdal, J.B. Sorensen, et al. (2008)
• Phase I clinical and pharmacokinetic study of the oral platinum analogue JM216 given daily for 14 days — C. Sessa, C. Minoia, et al. (1998)
• A first-in-human phase I dose-escalation, pharmacokinetic, and pharmacodynamic evaluation of intravenous LY2090314, a glycogen synthase kinase 3 inhibitor, administered in combination with pemetrexed and carboplatin — J.E. Gray, J.R. Infante, et al. (2015)

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