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

Our plain-English summary of 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, by B. Castagneto, S. Zai, L. Mutti, et al (Lung Cancer, 2001).

The study

• Authors: B. Castagneto, S. Zai, L. Mutti, A. Lazzaro, R. Ridolfi, E. Piccolini, A. Ardizzoni, L. Fumagalli, G. Valsuani, M. Botta
• Journal: Lung Cancer
• Published: 2001;31(2-3):303-10
• Cited by: 71 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma is often unresectable at diagnosis, is refractory to cytotoxic agents and is frequently complicated by pleural effusion. The expected survival range for patients with or without involvement of visceral pleura is respectively 1-9 and 9-12 months; mesothelioma-related pleural effusion severely impairs the patients' quality of life and easily relapses after conservative treatments. Intrapleural administration of IL-2 is reported to be effective both in tumor-associated malignant pleurisy and on primary mesothelioma, whereas few data exist about IL-2 systemic administration. In order to assess the palliative and therapeutic activity of IL-2 in unresectable pleural malignant mesothelioma with pleural effusion, we performed a phase II study on 31 consecutive patients (M/F 16/15; median age 61 years, range 40-84; PS ECOG 0 n=7; ECOG 1 n=15; ECOG 2 n=9; stage IA n=13; IB n=9; II n=7; IV=2) who received first-line therapy with intrapleural repeated instillation of 9000000 I.U. IL-2 twice/weekly for 4 weeks, after needle thoracenthesis. In nonprogressing patients, 3000000 I.U. IL-2 were subcutaneously administered thrice weekly for up to 6 months. Toxicity (WHO criteria) with intrapleural IL-2 consisted of grade 3 fever in 6/31 (19%) patients and of cardiac toxicity (failure) grade 3 in one patient (3%); toxicity during subcutaneous treatment was mild to moderate, mainly a flu-like syndrome. In 28/31 (90%) of patients there was no further or minimal (asymptomatic) pleural fluid collection (according to Paladine criteria); pleurisy relapsed only in 1/28 patients after 19 months. Tumor objective response (WHO criteria), evaluated by CT, occurred in seven patients (one CR and six PR; ORR 22%); ten patients achieved SD and 14 patients progressed. Median overall survival was 15 months (range 5-39) in all patients. IL-2 intrapleural administration followed by low-dose IL-2 subcutaneously in pleurisy-complicated malignant mesothelioma is feasible and active both in palliation of pleural effusion and on primary tumor, with manageable toxicity. The overall survival observed in nonprogressing patients warrants further randomized studies with IL-2 aimed to the patient outcome.

In plain English

This phase II study in Casale Monferrato, Italy, treated 31 consecutive patients with malignant pleural mesothelioma that could not be removed by surgery and that caused symptomatic fluid around the lung (pleural effusion). Enrollment ran from January 1994 to December 1996. All came from an area the authors described as at increased risk for asbestos pollution; 39% had been directly or indirectly exposed to asbestos through work or family. Patients received the immune drug interleukin-2 (IL-2) injected into the chest cavity. Those whose disease did not progress then received lower-dose IL-2 under the skin. Within 30 days, 28 of 31 patients (90%) had no further fluid or only a small amount that caused no symptoms and needed no drainage; in one of them, fluid returned after 19 months. Tumors shrank in 7 of 31 patients (22%, 95% confidence interval 9 to 41%), stayed stable in 10 and progressed in 14. Median overall survival was 15 months for all 31 patients. The authors concluded that intrapleural IL-2 was manageable and achieved long-term control of the effusion in a large number of patients.

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. Patients received intrapleural IL-2, 9,000,000 I.U. per injection, after needle drainage of the fluid. Patients whose disease did not progress then received subcutaneous IL-2, 3,000,000 I.U. three times weekly for up to 6 months.
• Who was studied: 31 consecutive patients (16 men, 15 women) with non-resectable malignant pleural mesothelioma and symptomatic pleurisy that came back after a single needle thoracentesis. They were enrolled January 1994 to December 1996 at a hospital in Casale Monferrato, Italy.
• Exposure: All patients came from Casale Monferrato, an area the authors describe as at increased risk for asbestos pollution. 12 of 31 patients (39%; five men, seven women) had been directly or indirectly exposed to asbestos for work or family reasons. No fiber type is named.
• Main results:
  • Response of the effusion was judged within 30 days. A complete response meant no further fluid collection within 30 days. A partial response meant only minimal fluid without symptoms that did not need further drainage within 30 days.
  • Pleural effusion: in 28 of 31 patients (90%) there was no further fluid collection, or only minimal fluid collection without symptoms. Treatment of the effusion failed in 3 patients (10%).
  • Among patients whose effusion responded, it came back in only one patient, 19 months after treatment.
  • Tumor response among the 31 patients: one complete response (3.2%) and six partial responses (19.3%), an overall response rate of 22% (95% confidence interval 9 to 41).
  • Disease was stable in 10 patients (32%). The other 14 patients had disease progression.
  • Median overall survival was 15 months for all 31 patients.
  • Median survival was 22 months (range 7 to 39) in the 7 responding patients and 20 months in the 10 patients with stable disease.
  • Median survival was 10.5 months (range 5 to 18) in the 14 patients whose disease progressed.
  • Fever during intrapleural therapy: grade 1 in 32%, grade 2 in 29% and grade 3 in 19% of patients.
  • One patient (3%) had grade 3 cardiac failure and recovered promptly after treatment.
  • Two patients developed grade 2 neuropathy during the subcutaneous maintenance therapy.
  • Eosinophilia was seen in 48% of patients; all cases were without symptoms.
• The authors' conclusion: The authors concluded that intrapleural IL-2 was manageable and could achieve long-term control of malignant pleural effusion in a large number of patients. They also concluded that it may induce tumor regression in about 20% and disease stabilisation in about 30% of non-selected patients. They called for a phase III study looking at overall survival and quality of life.
• Limitations the authors state:
  • The authors stated that their data were not sufficient to draw any conclusion about what the subcutaneous low-dose IL-2 maintenance added to the effect of intrapleural IL-2.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Pleural plaques and thickening.

Medical terms in this study, explained in our Lexicon: Palliative Care, Immunotherapy, Unresectable, Pleural Mesothelioma, Pleural Effusion, Visceral Pleura, Mesothelioma, Quality of Life.

Related studies

• 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)
• A phase II study of combined intravenous and subcutaneous interleukin-2 in malignant pleural mesothelioma — C.W. Mulatero, R.T. Penson, et al. (2001)
• 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)
• 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)
• 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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