Optimal management of malignant mesothelioma after subtotal pleurectomy: revisiting the role of intrapleural chemotherapy and postoperative radiation

Our plain-English summary of Optimal management of malignant mesothelioma after subtotal pleurectomy: revisiting the role of intrapleural chemotherapy and postoperative radiation, by E.R. Sauter, C. Langer, L.R. Coia, et al (Journal of Surgical Oncology, 1995).

The study

• Authors: E.R. Sauter, C. Langer, L.R. Coia, M. Goldberg, S.M. Keller
• Journal: Journal of Surgical Oncology
• Published: 1995;60(2):100-5
• Cited by: 35 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is a generally fatal disease with no standard treatment. There are encouraging reports using intraperitoneal chemotherapy to treat peritoneal mesotheliomas and intrapleural chemotherapy (IPC) to treat malignant pleural effusions. Our objective was to evaluate the efficacy of IPC after subtotal pleurectomy. Between 1988 and 1992, 20 consecutive patients with diffuse MPM limited to one hemithorax underwent subtotal pleurectomy. Thirteen patients with biopsy-proven MPM known prior to thoracotomy were enrolled in a phase II combined modality protocol consisting of perioperative intrapleural cisplatin (100 mg/m2) and ara-C (1,200 mg) after subtotal pleurectomy, followed by systemic cisplatin (50 mg/m2/week x 8) and mitomycin-C (8 mg/m2, days 1 and 36). Seven patients with MPM could not be enrolled because their diagnosis was made post-thoracotomy. These patients underwent subtotal pleurectomy with (n = 4) or without (n = 3) adjuvant radiation (4,500-5,000 cGy in 3 patients, 2,100 cGy in 1 patient). One of three patients who developed chemotherapy-related nephrotoxicity died, the only treatment-related mortality. All 3 patients requiring postoperative readmission received IPC. Significant morbidity did not occur in patients not receiving chemotherapy. Median survival and time to progression were significantly longer in patients not receiving IPC (21 vs. 9 months, P = 0.04; 12 vs. 6 months, P = 0.01). In conclusion, intrapleural and postoperative systemic chemotherapy resulted in significant toxicity and did not improve survival in our patients who underwent subtotal pleurectomy for MPM.

In plain English

This report described 20 consecutive patients at Fox Chase Cancer Center, Philadelphia, who had subtotal pleurectomy between 1988 and 1992 for diffuse malignant pleural mesothelioma limited to one side of the chest. Eighty percent reported direct asbestos exposure. Thirteen patients diagnosed before surgery were enrolled in a phase II protocol. They received cisplatin and ara-C placed into the pleural space at surgery, then systemic cisplatin and mitomycin-C, though only 7 of the 13 received the systemic treatment as planned. The other seven, diagnosed after surgery, had surgery alone (3) or surgery plus radiation (4). Median survival was 9 months with intrapleural chemotherapy and 21 months without (P = 0.04). Median time to progression was 6 versus 12 months (P = 0.01). Three chemotherapy patients developed kidney toxicity, and one of them died. The four radiation patients had a median survival of 38 months. The authors concluded that the chemotherapy caused significant toxicity and did not improve survival. They noted that selection bias might explain the differences and called for a larger trial of radiation.

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: Single-institution case series of 20 consecutive patients; 13 were treated on a phase II combined-treatment protocol and 7 were not enrolled (non-randomized comparison)
• Who was studied: 20 consecutive patients with diffuse malignant pleural mesothelioma limited to one hemithorax who underwent subtotal pleurectomy at Fox Chase Cancer Center, Philadelphia, 1988 to 1992. All were over 50 years old (median age 69) and 17 were male. 80% reported direct asbestos exposure.
• Exposure: The study examined treatments, not asbestos exposure. 13 patients received intrapleural cisplatin (100 mg/m2) and cytosine arabinoside (ara-C, 1,200 mg) at surgery, followed by systemic cisplatin (50 mg/m2/week for 8 weeks) and mitomycin-C (8 mg/m2 on days 1 and 36). 4 patients received postoperative radiation (4,500 to 5,000 cGy in 3; 2,100 cGy in 1). 3 had pleurectomy alone.
• Main results:
  • Median survival was 21 months in patients not receiving intrapleural chemotherapy vs 9 months in those receiving it (P = 0.04). Median time to progression was 12 vs 6 months (P = 0.01).
  • For all 20 patients, median survival was 12 months and 2-year survival was 25%.
  • Of the 13 patients who received intrapleural chemotherapy, only 7 went on to receive systemic chemotherapy according to plan.
  • In the chemotherapy group there were 6 treatment-related complications (46% morbidity) and one death (8% mortality). The death followed grade 4 kidney toxicity, sepsis and respiratory failure. Kidney toxicity (grade 2 in two patients, grade 4 in one) caused prolonged hospitalization.
  • Among patients who did not receive chemotherapy, none required prolonged hospitalization or readmission. Radiation caused grade 1 to 2 esophagitis.
  • Median survival was 38 months for the 4 patients who received postoperative radiation, 13 months for the 3 who had pleurectomy alone, and 9 months for those who received intrapleural chemotherapy.
  • Overall survival (P = 0.05) and time to progression (P = 0.04) were significantly longer in the 4 radiation patients than in the 16 who did not receive radiation.
  • The first site of disease progression was local in all 17 patients whose disease progressed.
  • Tumor histology did not influence survival (P = 0.38) or time to progression (P = 0.27).
  • Pleurectomy improved breathlessness in 47% of patients and pain in 21%. Only one patient required drainage of a recurrent pleural effusion.
• The authors' conclusion: The authors concluded that adjuvant chemotherapy was associated with poorer survival, and that this may have been due to the beneficial effects of radiotherapy or to selection bias. They described subtotal pleurectomy as a palliative operation with acceptable morbidity that prevents recurrent effusions and may temporarily reduce breathlessness but has little impact on chest wall pain. They stated that adjuvant radiotherapy should be studied in a larger phase II trial.
• Limitations the authors state:
  • The longer survival without chemotherapy may reflect selection bias. The seven non-chemotherapy patients were diagnosed only after surgery and may have had a more favorable prognosis.
  • The radiation finding rests on a small number of patients and may reflect selection bias.
  • Not all patients had formal lymph node removal, so TNM staging was not possible.
  • Information on indirect asbestos exposure through family members was unavailable.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Chemotherapy, Pleural Mesothelioma, Peritoneal Mesothelioma, Pleural Effusion, Hemithorax, Biopsy, Thoracotomy.

Related studies

• A phase II trial of pleurectomy/decortication followed by intrapleural and systemic chemotherapy for malignant pleural mesothelioma — V. Rusch, L. Saltz, et al. (1994)
• Pleurectomy/decortication and hyperthermic intrapleural chemotherapy for malignant pleural mesothelioma: initial experience — M. Migliore, D. Calvo, et al. (2015)
• Survival after trimodality therapy for malignant pleural mesothelioma: Radical Pleurectomy, chemotherapy with Cisplatin/Pemetrexed and radiotherapy — S. Bölükbas, C. Manegold, et al. (2011)
• Intrapleural cisplatin and mitomycin for malignant mesothelioma following pleurectomy: pharmacokinetic studies — V.W. Rusch, D. Niedzwiecki, et al. (1992)
• 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)
• Trimodality strategy for treating malignant pleural mesothelioma: results of a feasibility study of induction pemetrexed plus cisplatin followed by extrapleural pneumonectomy and postoperative hemithoracic radiation (Japan Mesothelioma Interest Group 0601 Trial) — S. Hasegawa, M. Okada, et al. (2016)

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