Weekly high-dose cisplatin in malignant pleural mesothelioma

Our plain-English summary of Weekly high-dose cisplatin in malignant pleural mesothelioma, by A.S. Planting, J.H. Schellens, S.H. Goey, et al (Annals of Oncology, 1994).

The study

• Authors: A.S. Planting, J.H. Schellens, S.H. Goey, M.E. van der Burg, M. de Boer-Dennert, G. Stoter, J. Verweij
• Journal: Annals of Oncology
• Published: 1994;5(4):373-4
• Cited by: 40 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Cisplatin at conventional doses has marginal activity in mesothelioma. A dose-response relation for cisplatin has been suggested in other tumor types. In a phase I study on weekly cisplatin administration, 3 of 5 patients with mesothelioma responded. Therefore, a phase II study with weekly cisplatin was started with the recommended dose of 80 mg/m2/week for six weeks.

Patients And Methods: Fourteen patients with mesothelioma stage II, with measurable lesions, were treated with cisplatin at a dose of 80 mg/m2 weekly for six weeks. Cisplatin was administered in 3% NaCl and combined with ondansetron as antiemetic.

Results: Five patients had partial responses (response rate 36%; 95% confidence interval 12%-65%) lasting 2-8 months. Seven patients had stable disease. Ototoxicity, grade 2 in 3 patients and grade 3 in 2, was the most troublesome side effect.

Conclusions: Cisplatin given at a higher dose intensity than in conventional schedules is active in mesothelioma. The response duration is short, however, possibly due to lack of effective maintenance therapy.

In plain English

This short report from Rotterdam, the Netherlands, described a phase II study of the chemotherapy drug cisplatin in malignant pleural mesothelioma. The article did not discuss asbestos exposure. Fourteen men with pleural mesothelioma who had not had chemotherapy before were scheduled to receive cisplatin at 80 mg/m2 once a week for six weeks, in 3% salt solution, together with the anti-nausea drug ondansetron. Five patients had partial responses, a response rate of 36% (95% confidence interval 12%-65%). These responses lasted 2, 4, 6, 6 and 8 months. Seven patients had stable disease for a median of 12 weeks. Six of the 14 patients completed treatment within six weeks: two received only four doses, one missed the sixth, and some had delays. The average dose given was 69 mg/m2 per week. Hearing damage (ototoxicity) reached grade 2 in 3 patients and grade 3 in 2. The authors called it a concern because hearing loss is usually permanent. Low platelet counts reached grade 3 in 4 patients and grade 4 in 1. The authors concluded that weekly cisplatin was worth studying further, though responses were short-lived.

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: phase II treatment study (short report)
• Who was studied: 14 male patients with histologically proven pleural mesothelioma and no prior chemotherapy, treated at the Rotterdam Cancer Institute/Dr. Daniel den Hoed Kliniek, Rotterdam, the Netherlands; median age 63 (range 41-70); study dates not given
• Exposure: No asbestos exposure is reported. The planned treatment was cisplatin 80 mg/m2 in 250 ml of 3% hypertonic saline over 3 hours, weekly for 6 weeks, with an 8 mg ondansetron bolus as antiemetic
• Main results:
  • Five of the 14 patients had partial responses (response rate 36%; 95% confidence interval 12%-65%)
  • The five partial responses lasted 2, 4, 6, 6 and 8 months
  • Seven patients had stable disease, for a median duration of 12 weeks (range 8-24 weeks)
  • Not all patients received the full planned treatment: two received 4 doses because of early progressive disease, one had the sixth dose cancelled because of slow platelet recovery, and doses were delayed in 5 patients because of thrombocytopenia
  • Six patients completed treatment in 6 weeks; the mean cisplatin dose intensity reached was 69 mg/m2/week (range 53-80)
  • Ototoxicity was grade 2 in 3 patients and grade 3 in 2 patients
  • Thrombocytopenia (low platelets) was grade 3 in 4 patients and grade 4 in 1 patient; none required a platelet transfusion
  • Nausea and vomiting were effectively controlled by ondansetron only during the first 3-4 administrations
• The authors' conclusion: The authors concluded that weekly cisplatin is worth studying further in mesothelioma, because the response rate compared favourably with other cisplatin studies, though responses were short
• Limitations the authors state:
  • The authors noted that responses were of limited duration, possibly because treatment was not continued
  • The authors noted that ototoxicity is a concern because clinical hearing loss is usually irreversible

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, Pleural Mesothelioma, Mesothelioma, Dose-response relationship, confidence interval, Ototoxicity.

Related studies

• Combined systemic chemoimmunotherapy in advanced diffuse malignant mesothelioma. Report of a phase I-II study of weekly cisplatin/interferon alfa-2a — P. Soulié, P. Ruffié, et al. (1996)
• Weekly systemic combination of cisplatin and interferon alpha 2a in diffuse malignant pleural mesothelioma — A. Purohit, L. Moreau, et al. (1998)
• 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)
• High liposomal doxorubicin tumour tissue distribution, as determined by radiopharmaceutical labelling with (99m)Tc-LD, is associated with the response and survival of patients with unresectable pleural mesothelioma treated with a combination of liposomal doxorubicin and cisplatin — O. Arrieta, L.A. Medina, et al. (2014)
• Phase I trial of tirapazamine in combination with cisplatin in a single dose every 3 weeks in patients with solid tumors — C.A. Johnson, D. Kilpatrick, et al. (1997)
• 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)

Browse more research in Annals of Oncology, or return to medical research.