Intrapleural recombinant IL-2 in passive immunotherapy for malignant pleural effusion

Our plain-English summary of Intrapleural recombinant IL-2 in passive immunotherapy for malignant pleural effusion, by P. Astoul, J.R. Viallat, J.C. Laurent, et al (Chest, 1993).

The study

• Authors: P. Astoul, J.R. Viallat, J.C. Laurent, M. Brandely, C. Boutin
• Journal: Chest
• Published: 1993;103(1):209-13
• Cited by: 78 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The purpose of this phase 1 study was to determine the toxicity and effectiveness of recombinant interleukin-2 (RU 49637 Roussel Uclaf-France) administered by continuous pleural infusion for 5 days to patients with different histologic subtypes of pleural cancer. Incremental doses of rIL-2 from 3 x 10(6) to 24 x 10(6) were given via a thin catheter inserted into the homolateral pleural cavity. Patients were evaluated before treatment and 36 days after treatment by computed tomography scan and thoracoscopy with biopsy. Twenty-two patients with malignant pleural effusion (15 malignant pleural mesotheliomas, 6 adenocarcinomas, 1 squamous cell carcinoma) were treated. The maximum tolerated dose (MTD) of rIL-2, defined as the dose that produced grade 3 or greater toxic reactions in 50 percent of the patients, was 24 x 10(6) IU/m2/d. Although some side effects were encountered at any dose, tolerance was acceptable. The main side effect was fluid retention (8 of 22) which never exceeded 10 percent of body weight. Responses were achieved in 10 out of 22 patients with 1 complete remission (mesothelioma) and 9 partial remissions (3 adenocarcinomas and 6 malignant pleural mesotheliomas). Based on these results, we recommend that phase 2 studies using rIL-2 at a dose of 21 x 10(6) IU/m2/d via the intrapleural route be undertaken.

In plain English

This was a phase 1 trial in Marseille, France, testing recombinant interleukin-2 (rIL-2), an immune-system drug, infused continuously into the pleural (chest) cavity for 5 days. It treated 22 previously untreated patients with malignant pleural effusion: 15 with malignant pleural mesothelioma, 6 with adenocarcinoma and 1 with squamous cell carcinoma. Doses were raised step by step from 3 million to 24 million IU per square meter per day. The maximum tolerated dose was 24 million IU per square meter per day. Fluid retention occurred in 8 of 22 patients and never exceeded 10 percent of body weight. One patient at 21 million had a myocardial infarction requiring intensive care. The authors note that this patient had a history of angina and should not have been included. Of 20 patients evaluated, 10 had remissions. Among the 15 mesothelioma patients, 7 had remissions, all with the epithelial type. Two died before evaluation. Three of seven patients with metastatic pleural cancer had remissions. The authors concluded that rIL-2 can benefit selected patients and recommended phase 2 studies at 21 million IU per square meter per day. Asbestos exposure was not studied.

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 1 dose-escalation trial of intrapleural recombinant interleukin-2
• Who was studied: 22 previously untreated patients with histologically documented malignant pleural effusion (16 men, 6 women; median age 58.9 years) treated in Marseille, France. Causes: mesothelioma in 15 (11 epithelial, 1 fibrosarcomatous, 3 mixed), primary adenocarcinoma in 2, secondary adenocarcinoma in 4, secondary squamous cell carcinoma in 1.
• Exposure: Not an asbestos exposure study. The treatment studied was recombinant interleukin-2 infused continuously into the pleural cavity through a thin catheter for 5 days, at doses rising from 3 million to 24 million IU per square meter per day.
• Main results:
  • The maximum tolerated dose by the intrapleural route was 24 x 10^6 (24 million) IU per square meter per day; three patients were treated at this dose.
  • Fluid retention occurred in 8 of 22 patients and never exceeded 10 percent of body weight.
  • One patient (patient 18, mixed mesothelioma) treated at 21 million IU per square meter per day developed a myocardial infarction on day 5 requiring intensive care.
  • Two patients, both with mesothelioma, died before evaluation.
  • Of the 20 patients evaluated at 36 days, 10 achieved remission.
  • One complete response was recorded: patient 7 (epithelial mesothelioma), whose pleura showed no malignant cells at surgery.
  • Of the 15 malignant mesothelioma patients, 7 achieved remission. All 7 had the epithelial type.
  • Among mesothelioma patients, all three with stage I disease and four of eight with stage II disease had remissions, and those in more advanced stages did not respond. Mean survival after diagnosis was 21.1 months for mesothelioma responders and 4.4 months for nonresponders.
  • Of the seven patients with metastatic pleural cancer, three achieved remission.
• The authors' conclusion: The authors believed that rIL-2 immunotherapy can benefit selected patients with malignant pleural tumors and can be given safely in a conventional pulmonology unit. They recommended phase 2 studies of intrapleural rIL-2 at 21 x 10^6 IU per square meter per day.
• Limitations the authors state:
  • The patient who had a myocardial infarction had a history of angina pectoris and, the authors state, should not have been included in the trial.

Topics

Medical terms in this study, explained in our Lexicon: Immunotherapy, Pleural Effusion, Histological Subtype, Pleural Cavity, Thoracoscopy, Biopsy, Pleural Mesothelioma, Adenocarcinoma.

Related studies

• 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 cisplatin and cytarabine in the management of malignant pleural effusions: a Lung Cancer Study Group trial — V.W. Rusch, R. Figlin, et al. (1991)
• The efficacy of pemetrexed and bevacizumab intrapleural injection for malignant pleural mesothelioma-mediated malignant pleural effusion — D. Chen, X. Li, et al. (2014)
• NK cells from malignant pleural effusions are not anergic but produce cytokines and display strong antitumor activity on short-term IL-2 activation — P. Vacca, S. Martini, et al. (2013)
• 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)
• Asbestos and cancer: human natural killer cell activity is suppressed by asbestos fibers but can be restored by recombinant interleukin-2 — B.W. Robinson (1989)

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