Phase III randomized trial of surgery with or without intraoperative photodynamic therapy and postoperative immunochemotherapy for malignant pleural mesothelioma

Our plain-English summary of Phase III randomized trial of surgery with or without intraoperative photodynamic therapy and postoperative immunochemotherapy for malignant pleural mesothelioma, by H.I. Pass, B.K. Temeck, K. Kranda, et al (Annals of Surgical Oncology, 1997).

The study

• Authors: H.I. Pass, B.K. Temeck, K. Kranda, G. Thomas, A. Russo, P. Smith, W. Friauf, S.M. Steinberg
• Journal: Annals of Surgical Oncology
• Published: 1997;4(8):628-33
• Type of article: Randomized trial
• Cited by: 147 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Patients with malignant pleural mesothelioma (MPM) usually die of progressive local disease. This report describes the results of a Phase III trial comparing maximum debulking surgery and postoperative cisplatin, interferon alpha-2b, and tamoxifen (CIT) immunochemotherapy with and without intraoperative photodynamic therapy (PDT) to determine (1) whether such a multimodal approach can be performed with minimum morbidity and mortality in malignant pleural mesothelioma (MPM), and (2) whether first-generation (i.e., 630-nm laser light, Photofrin II) intrapleural PDT impacts on local recurrence of survival.

Methods: From July 1993 to June 1996, 63 patients with localized MPM were randomized to either PDT or no PDT. The tumors of 15 patients could not be debulked to 5 mm. Patients assigned to PDT (n = 25) and no PDT (n = 23) were similar with respect to age, sex, tumor volume, and histology.

Results: The type of resection (11 pleurectomies and 14 pneumonectomies vs. 12 pleurectomies and 11 pneumonectomies), length postoperative stay, and ICU time were comparable (PDT vs. no PDT). There was one operative death (hemorrhage), and each group had two bronchopleural fistulas. Postoperative staging divided patients into the following categories: stage I: PDT, 2, no PDT, 2; stage II: PDT, 2, no PDT, 2; stage III, PDT, 21; no PDT, 17; stage IV, PDT, 0; no PDT, 2. Comparable numbers of CIT cycles were delivered. Median survival for the 15 non-debulked patients was 7.2 months, compared to 14 months for the 48 patients on protocol. There were no differences in median survival (14.4 vs. 14.1 months) or median progression-free time (8.5 vs. 7.7 months), and sites of first recurrence were similar.

Conclusions: Aggressive multimodal therapy can be delivered for patients with higher stage MPM. First-generation PDT does not prolong survival or increase local control for MPM.

In plain English

This Phase III randomized trial took place at the National Cancer Institute in Bethesda, Maryland. Between July 1993 and June 1996, 63 patients with malignant pleural mesothelioma were registered and randomized. Most had a history of asbestos exposure. Surgery aimed to leave no tumor thicker than 5 mm anywhere in the chest. This was followed by immunochemotherapy with cisplatin, interferon alpha-2b and tamoxifen. The randomization decided whether patients also received photodynamic therapy during surgery, which combines a light-activated drug (Photofrin II) with 630-nm laser light. Fifteen patients were taken off study (8 could not be debulked to 5 mm, 6 progressed before surgery, 1 withdrew), leaving 25 with photodynamic therapy and 23 without. Median survival was 14.1 months with photodynamic therapy and 14.4 months without, and the difference was not significant. Median recurrence-free survival was 8.5 and 7.7 months, and sites of first recurrence were similar. Complications and chemotherapy side effects did not differ between groups; there was one operative death. The trial stopped early, short of its planned 88 patients. The authors concluded that first-generation photodynamic therapy does not prolong survival or increase local control.

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 III randomized controlled trial (surgery plus postoperative immunochemotherapy, with versus without intraoperative photodynamic therapy)
• Who was studied: 63 patients with malignant pleural mesothelioma were registered and randomized at the National Cancer Institute, Bethesda, Maryland, from July 1993 to June 1996. 15 were taken off study, leaving 48 evaluable (25 photodynamic therapy, 23 no photodynamic therapy). There were 45 males and 18 females, and the majority had a history of asbestos exposure.
• Exposure: The treatment studied was intraoperative photodynamic therapy: Photofrin II 2 mg/kg intravenously 24 hours before surgery, then 630-nm laser light at a cumulative dose of 30 J/cm2 at each measuring site. All patients had surgical debulking (pleurectomy or extrapleural pneumonectomy) aiming for residual tumor no more than 5 mm thick at any intrathoracic site, followed by postoperative cisplatin, interferon alpha-2b and tamoxifen. Asbestos exposure is mentioned only as a patient characteristic.
• Main results:
  • Median survival was 14.1 months in the photodynamic therapy group and 14.4 months in the no photodynamic therapy group, with no significant difference. The median for all 48 evaluable patients was 14.4 months.
  • Median recurrence-free survival was 8 months for the entire group: 8.5 months with photodynamic therapy and 7.7 months without.
  • Recurrence patterns did not differ. First recurrence was local in 18 of 25 photodynamic therapy patients (72%) and in 16 of 23 no photodynamic therapy patients (70%).
  • The 15 patients taken off study, described by the authors as those whose tumors could not be surgically cytoreduced, had a median survival of 7.2 months.
  • Complications of surgery or immunochemotherapy did not differ between groups. There were 11 postoperative complications in 10 patients, including two bronchopleural fistulas in each group. There was one operative death, in a photodynamic therapy patient whose inferior vena cava avulsed.
  • Photodynamic therapy added 137 minutes to the operation. Measured tumor porphyrin levels were significantly higher in the photodynamic therapy group: 673 plus or minus 43 pg/mg tissue in 22 patients, versus 332 plus or minus 61 pg/mg in 19 no photodynamic therapy patients.
• The authors' conclusion: The authors concluded that aggressive multimodal therapy can be delivered to patients with higher-stage malignant pleural mesothelioma, and that first-generation photodynamic therapy does not prolong survival or increase local control. They added that the technique should not be discarded, because newer sensitizers and light delivery could improve it.
• Limitations the authors state:
  • The trial was stopped early because the principal investigator relocated. It did not reach the planned 44 patients per arm (88 total), and only 48 patients were evaluable. The authors judged that the smaller sample probably had minimal impact, given how similar the results were.

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, Cytoreductive Surgery, Cisplatin, Histology, Staging, Median Survival, Multimodal Therapy.

Related studies

• Radical pleurectomy and intraoperative photodynamic therapy for malignant pleural mesothelioma — J.S. Friedberg, M.J. Culligan, et al. (2012)
• A preclinical model to investigate the role of surgically-induced inflammation in tumor responses to intraoperative photodynamic therapy — R.W. Davis, E. Papasavvas, et al. (2018)
• Combination effect of photodynamic therapy using NPe6 with pemetrexed for human malignant pleural mesothelioma cells — S. Maehara, J. Usuda, et al. (2015)
• Intraoperative photodynamic therapy for malignant mesothelioma — H.I. Pass, Z. Tochner, et al. (1990)
• Randomized phase II trial of pemetrexed/cisplatin with or without CBP501 in patients with advanced malignant pleural mesothelioma — L.M. Krug, A.J. Wozniak, et al. (2014)
• A Novel Prospective Study Assessing the Combination of Photodynamic Therapy and Proton Radiation Therapy: Safety and Outcomes When Treating Malignant Pleural Mesothelioma — S.R. Rice, Y.R. Li, et al. (2019)

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