Intrapleural administration of interleukin 2 in pleural mesothelioma: a phase I-II study

Our plain-English summary of Intrapleural administration of interleukin 2 in pleural mesothelioma: a phase I-II study, by S.H. Goey, A.M. Eggermont, C.J. Punt, et al (British Journal of Cancer, 1995).

The study

• Authors: S.H. Goey, A.M. Eggermont, C.J. Punt, R. Slingerland, J.W. Gratama, R. Oosterom, R. Oskam, R.L. Bolhuis, G. Stoter
• Journal: British Journal of Cancer
• Published: 1995;72(5):1283-8
• Cited by: 84 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Twenty-three patients with pleural mesothelioma stage I-IIA were entered in a study of continuous daily intrapleural infusion of interleukin 2 (IL-2) for 14 days, repeated every 4 weeks. IL-2 was administered according to a groupwise dose escalation schedule (group A, 3 x 10(4); group B, 3 x 10(5); group C, 3 x 10(6); group D, 6 x 10(6); group E, 18 x 10(6); and group F, 36 x 10(6) IU day-1). Each group consisted of at least three patients. Intrapleural administration of IL-2 was associated with acceptable toxicity. All patients were treated on an outpatient basis except for the patients at dose levels E and F. Dose-limiting toxicity was observed at level F, 36 x 10(6) IU daily, and consisted of catheter infection, fever and flu-like symptoms. Intrapleural IL-2 levels were high (> 20,000 IU ml-1) at levels E and F, while serum levels in most patients were not or barely detectable (< 3-30 IU ml-1). Intrapleural IL-2 levels were up to 6000-fold higher than systemic levels. Intrapleural tumour necrosis factor alpha (TNF-alpha) levels varied greatly and did not correlate with IL-2 dosage. Intrapleural mononuclear cells (MNCs) displayed IL-2-induced lymphokine-activated killer (LAK) activity in all patients. Two patients were not evaluable for response owing to catheter-related problems which precluded the delivery of IL-2. Partial response (PR) occurred in 4 of 21 evaluable patients (19%; 95% confidence interval 5-42%) with a median time to progression of 12 months (range 5-37). Stable disease (SD) occurred in seven patients with a median time to progression of 5 months (range 2-7). There were no complete responses (CRs). The median overall survival was 15.6 months (range 3.0-43). No relationship between the dose of IL-2 and response rate was observed. We conclude that IL-2 given intrapleurally is accompanied with acceptable toxicity and has anti-tumour activity against mesothelioma. In view of the refractory nature of the disease IL-2 may be a treatment option for mesothelioma. A formal phase II study is warranted. Based on the observed toxicity, the lack of dose-response relationship and the immunomodulatory effects seen at relatively low-dose IL-2, the recommended dose for a phase II study is 3 x 10(6) IU day-1 using the present treatment schedule.

In plain English

This phase I-II study tested interleukin 2 (IL-2), an immune-system protein, given as a continuous infusion into the chest cavity for 14 days, repeated every 4 weeks. It enrolled 23 men with untreated epithelial-type malignant pleural mesothelioma, stage I or IIA. Most were shipyard workers with a history of asbestos exposure. Doses rose across six groups, from 3 x 10^4 to 36 x 10^6 international units per day. At the highest dose, catheter infection, fever and flu-like symptoms limited treatment. Overall, seven patients had infected catheters, four of them at that dose. Of 21 evaluable patients, 4 had a partial response (19%; 95% confidence interval 5-42%), with a median time to progression of 12 months. None had a complete response. Median overall survival was 15.6 months. Response did not correlate with dose. The authors concluded that intrapleural IL-2 had acceptable toxicity and anti-tumour activity. They suggested 3 x 10^6 units per day for a phase II study, while noting small group sizes and frequent empyema.

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 treatment study (no comparison group)
• Who was studied: 23 male patients with untreated epithelial-type malignant pleural mesothelioma, stage I or IIA (Butchart staging); median age 57 (range 47-71); 21 were evaluable
• Exposure: The treatment studied was recombinant human IL-2 given into the pleural cavity at six dose levels (3 x 10^4 to 36 x 10^6 IU per day). On asbestos, the article says only that most patients were shipyard workers with a history of asbestos exposure; no fiber types are given.
• Main results:
  • Partial response in 4 of 21 evaluable patients (19%; 95% confidence interval 5-42%), with a median time to progression of 12 months (range 5-37)
  • No complete responses
  • Stable disease in seven patients (as stated in the text), with a median time to progression of 5 months (range 2-7)
  • Median overall survival 15.6 months (range 3.0-43)
  • Dose of IL-2 did not correlate with response
  • Dose-limiting toxicity at level F (36 x 10^6 IU daily): catheter infection, fever and flu-like symptoms; this dose was not tolerated by four of the five patients started on it
  • Infection of the Port-a-cath catheter system in seven patients, four of them at the highest dose; five of the seven showed clinical signs of empyema
  • Intrapleural IL-2 levels were up to 6000-fold higher than levels in the blood
  • No differences in LAK (killer-cell) activity were seen between responders and non-responders
  • The authors suggested a daily dose of 3 x 10^6 IU of IL-2 for a phase II study
• The authors' conclusion: The authors concluded that intrapleural IL-2 is accompanied by acceptable toxicity and has anti-tumour activity against mesothelioma, and that a formal phase II study is warranted
• Limitations the authors state:
  • Small numbers of patients in each dose group and frequent empyema made recommending a dose difficult
  • It is uncertain whether, and how far, catheter-related infections contributed to the anti-tumour responses
  • CT scans did not show tumour shrinkage in some patients whose tissue showed extensive tumour necrosis, which makes response hard to judge in mesothelioma
  • Three patients received additional cisplatin and etoposide, so their progression-free survival could not be determined

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, Necrosis, confidence interval, Median Overall Survival, Mesothelioma, Dose-response relationship.

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)
• Intrapleural interleukin-2 induces nitric oxide production in pleural effusions from malignant mesothelioma: a possible mechanism of interleukin-2-mediated cytotoxicity? — C. Porta, V. Rizzo, et al. (2002)
• A phase II study of combined intravenous and subcutaneous interleukin-2 in malignant pleural mesothelioma — C.W. Mulatero, R.T. Penson, et al. (2001)
• 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)
• Safety, feasibility and therapeutic activity of intrapleural autologous lymphocyte conditioned medium followed by systemic recombinant interleukin-2 and interferon-alpha in a patient with malignant pleural mesothelioma — S. Duensing, H. Hamm, et al. (1997)
• Intrapleural recombinant IL-2 in passive immunotherapy for malignant pleural effusion — P. Astoul, J.R. Viallat, et al. (1993)

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