A phase II study of combined intravenous and subcutaneous interleukin-2 in malignant pleural mesothelioma

Our plain-English summary of A phase II study of combined intravenous and subcutaneous interleukin-2 in malignant pleural mesothelioma, by C.W. Mulatero, R.T. Penson, D. Papamichael, et al (Lung Cancer, 2001).

The study

• Authors: C.W. Mulatero, R.T. Penson, D. Papamichael, N.H. Gower, M. Evans, R.M. Rudd
• Journal: Lung Cancer
• Published: 2001;31(1):67-72
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

A total of 29 previously untreated patients with histologically proven malignant pleural mesothelioma, with an ECOG score of < or = 2 and UICC stage I-II disease, were enrolled between May 1994 and October 1996. On days 1 and 2, 18 x 10(6) IU/day of rIL-2 was administered by continuous intravenous infusion, and 6 x 10(6) IU/day of rIL-2 by subcutaneous injection on days 5--20 inclusive of a 42-day cycle. Further treatment was administered if no radiological disease progression was demonstrated. A total of 29 patients were assessable for toxicity and 25 for response, and 49 cycles of IL-2 were administered with a median of one per patient (range, < 1-4). Toxicity included mild fever, nausea and vomiting, and skin rashes, < grade II. Three patients failed to complete one cycle of treatment because of toxicity and one died of disease before response evaluation. Two patients achieved a partial response (8%, 95% CI 1-26%) surviving 18.1 and 18.7 months from diagnosis. A total of 11 patients (44%, 95% CI 24-65%) with stable disease had a median survival of 13.6 months (range 6.5-33.8). The median survival was 8.6 months (range 3.7-34.5) for the 12 patients with progressive disease (48%, 95% CI 28-69%). This regimen of rIL-2 is well tolerated and shows limited activity in mesothelioma.

In plain English

This phase II trial in London tested recombinant interleukin-2 (rIL-2), an immune-system drug, in malignant pleural mesothelioma. Between May 1994 and October 1996, 29 previously untreated patients with stage I or II disease were enrolled. Each 42-day cycle began with two days of intravenous rIL-2, then, after a two-day break, daily injections under the skin (15 days per the methods; days 5 to 20 per the abstract). Side effects were mostly mild; fever reached grade II in 15 cases, controlled with paracetamol. Three patients stopped during their first cycle because of toxicity, though one patient's suspected drug-related arthritis proved to be rheumatoid arthritis. Of 25 patients assessed for response, 2 with epithelial tumors had a partial response (8%, 95% confidence interval 1 to 26%). Eleven (44%, confidence interval 24 to 65%) had stable disease, median survival 14 months. Twelve (48%, confidence interval 28 to 69%) progressed, median survival 9 months. By July 1999 all but one had died of disease. The authors called the response rate disappointing but concluded that the two partial responses support some activity of rIL-2.

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 single-arm treatment trial
• Who was studied: 29 previously untreated patients with histologically proven malignant pleural mesothelioma, UICC stage I or II, aged 18 to 70 at entry (25 men, 4 women; median age 61), enrolled at St Bartholomew's Hospital, London, between May 1994 and October 1996
• Exposure: Treatment with recombinant interleukin-2. Patients received 18 million IU per day by continuous intravenous infusion on days 1 and 2. After 48 hours with no treatment, they received 6 million IU per day by subcutaneous injection. The methods give this as 15 consecutive days; the abstract gives it as days 5 to 20 inclusive. Each cycle lasted 42 days. A history of asbestos exposure was taken at baseline, but no exposure results were reported.
• Main results:
  • 49 cycles of rIL-2 were given in total, a median of one per patient.
  • Of all 29 patients, 3 failed to complete one cycle because of toxicity. In one of these 3, the arthritis first suspected to be drug-related later proved to be rheumatoid arthritis.
  • The main toxicity was fever without infection, which reached WHO grade II in 15 cases and was controlled with paracetamol.
  • Of 25 patients assessed for response, 2 with epithelial mesothelioma achieved a partial response (8%, 95% CI 1 to 26%).
  • 11 of 25 assessed patients had stable disease (44%, 95% CI 24 to 65%), with a median survival of 14 months (range 7 to 34).
  • 12 of 25 assessed patients progressed on treatment (48%, 95% CI 28 to 69%). The results section gives their median survival as 9 months (range 4 to 35).
  • For all 29 patients, median survival was 9 months (range 1 to 41) from the first IL-2 dose and 12 months (range 4 to 42) from diagnosis.
  • As of July 1999, all but one patient had died of disease.
• The authors' conclusion: The authors concluded that the response rate to systemic rIL-2 was disappointing, but that the two partial responses support some activity of the drug against 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: Pleural Mesothelioma, UICC, Disease Progression, Median Survival, Mesothelioma.

Related studies

• Interleukin-2 in malignant pleural mesothelioma (and adenocarcinoma of the lung). The use of intrapleural and continuous intravenous infusions: preliminary results — N. Thatcher, P. Taylor, et al. (1989)
• Palliative and therapeutic activity of IL-2 immunotherapy in unresectable malignant pleural mesothelioma with pleural effusion: Results of a phase II study on 31 consecutive patients — B. Castagneto, S. Zai, et al. (2001)
• Combined epirubicin and interleukin-2 regimen in the treatment of malignant mesothelioma: a multicenter phase II study of the Italian Group on Rare Tumors — S. Bretti, A. Berruti, et al. (1998)
• Progress report on the palliative therapy of 100 patients with neoplastic effusions by intracavitary low-dose interleukin-2 — P. Lissoni, M. Mandalà, et al. (2001)
• Enhanced interleukin activity following asbestos inhalation — D.P. Hartmann, M.M. Georgian, et al. (1984)
• Eosinophil colony-stimulating factor induced by administration of interleukin-2 into the pleural cavity of patients with malignant pleurisy — Y. Nakamura, T. Ozaki, et al. (1990)

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