Phase I/II study of a short course of weekly cisplatin in patients with advanced solid tumours

Our plain-English summary of Phase I/II study of a short course of weekly cisplatin in patients with advanced solid tumours, by A.S. Planting, M.E. van der Burg, M. de Boer-Dennert, et al (British Journal of Cancer, 1993).

The study

• Authors: A.S. Planting, M.E. van der Burg, M. de Boer-Dennert, G. Stoter, J. Verweij
• Journal: British Journal of Cancer
• Published: 1993;68(4):789-92
• Cited by: 30 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Twenty-five patients with advanced solid tumours were entered in a phase I/II study of six, weekly cycles of cisplatin. Nineteen patients were chemonaive and six were previously treated. The starting dose was 50 mg m-2 week-1. This dose could be escalated without major toxicity to 70 mg m-2 week-1. At a dose of 80 mg m-2 myelosuppression grade 3 occurred as well as grade 1 nephro- and neurotoxicity. The maximum tolerated dose was 85 mg m-2 with dose limiting thrombocytopenia. Hypertonic saline was effective in preventing nephrotoxicity. Ondansetron was a very effective antiemetic in the first weeks of treatment but its efficacy waned later on. Responses were observed in head and neck cancer, melanoma and mesothelioma. At the dose level of 80 mg m-2 the optimal dose intensity was reached. This schedule will be tested further in phase II studies.

In plain English

This was a phase I/II trial in Rotterdam, the Netherlands. It tested weekly cisplatin, a cancer drug, for six weeks, in 3% salt solution with the anti-nausea drug ondansetron. Twenty-five patients with advanced solid tumours took part, seven with pleural mesothelioma. The article does not discuss asbestos. Doses were raised stepwise from 50 to 85 mg per square metre of body surface per week. At 50 to 70 mg per square metre per week, side effects were mild to moderate. At 85 mg per square metre per week, four of seven patients had grade 4 low platelets; one lung cancer patient died of sepsis and pneumonia. Ondansetron worked well at first but waned later. Of 24 patients assessed for response, four of seven with mesothelioma had a partial response, as did eight of nine with locally advanced head and neck cancer. The authors concluded that weekly cisplatin was feasible. For phase II studies they proposed 80 mg per square metre per week for six weeks in previously untreated patients, and said randomised studies were needed to establish clinical benefit.

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 I/II dose-escalation trial of weekly cisplatin (six weekly cycles)
• Who was studied: 25 patients with metastatic or locally advanced solid tumours at the Rotterdam Cancer Institute/Daniel den Hoed Kliniek, Netherlands. Table I lists 7 with pleural mesothelioma, plus head and neck cancer, lung squamous cell carcinoma, sarcoma, melanoma and adenocarcinoma of unknown primary. Six had prior non-cisplatin chemotherapy.
• Exposure: Cisplatin given weekly for 6 weeks in 3% hypertonic saline at dose levels of 50, 60, 70, 80 and 85 mg per square metre per week, with ondansetron as antiemetic. Asbestos exposure was not studied.
• Main results:
  • At 50, 60 and 70 mg per square metre per week, toxicity was mild to moderate.
  • The exception was one patient at 70 mg per square metre per week, who did not receive the sixth cycle because platelets recovered slowly.
  • At 85 mg per square metre per week, grade 4 thrombocytopenia (low platelets) occurred in 4 of 7 patients. One patient with obstructive lung cancer died of sepsis and pneumonia.
  • Grade 1 nephrotoxicity (kidney toxicity) occurred in 8 patients, only at the 80 and 85 mg per square metre dose levels.
  • Grade 3 ototoxicity (hearing loss requiring a hearing aid) occurred in 2 patients at 85 mg per square metre per week.
  • Ondansetron prevented nausea and vomiting well early in treatment, but its effect waned over the last two to three cisplatin doses.
  • Among the 24 patients evaluable for response, 4 of 7 mesothelioma patients had a partial response. The article gives response durations of 2, 4 and 8 months.
  • Partial responses occurred in 8 of 9 patients with locally advanced head and neck cancer and in 2 of 3 with recurrent or metastatic head and neck cancer. One melanoma patient had a complete response.
  • The 80 mg per square metre level reached the same mean dose intensity (70 mg per square metre per week) as the 85 mg per square metre level, with less toxicity.
• The authors' conclusion: The authors concluded that weekly cisplatin for 6 weeks was feasible. Given in hypertonic saline with a 5-HT3 antagonist, it reached a higher dose intensity than previously reported weekly schedules. They proposed 80 mg per square metre per week for 6 weeks for phase II studies in previously untreated patients.
• Limitations the authors state:
  • Response duration could not be determined for most head and neck cancer patients because they were irradiated afterwards.
  • Randomised studies comparing this schedule with standard cisplatin schedules are needed to establish clinical benefit.

Topics

Medical terms in this study, explained in our Lexicon: Cisplatin, Nephrotoxicity, Mesothelioma.

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 high-dose cisplatin in malignant pleural mesothelioma — A.S. Planting, J.H. Schellens, et al. (1994)
• A phase I pharmacokinetic and pharmacodynamic study of the oral mitogen-activated protein kinase kinase (MEK) inhibitor, WX-554, in patients with advanced solid tumours — D. Jamieson, M.J. Griffin, et al. (2016)
• Phase I and pharmacologic study of CT-2584 HMS, a modulator of phosphatidic acid, in adult patients with solid tumours — S.L. Cheeseman, M. Brannan, et al. (2000)
• 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)
• Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study — A. Marabelle, M. Fakih, et al. (2020)

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