High-dose methotrexate in the treatment of malignant mesothelioma of the pleura. A phase II study

Our plain-English summary of High-dose methotrexate in the treatment of malignant mesothelioma of the pleura. A phase II study, by O.P. Solheim, G. Saeter, A.M. Finnanger, et al (British Journal of Cancer, 1992).

The study

• Authors: O.P. Solheim, G. Saeter, A.M. Finnanger, A.E. Stenwig
• Journal: British Journal of Cancer
• Published: 1992;65(6):956-60
• Cited by: 110 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

From 1984 to 1989, 63 patients with diffuse, malignant mesothelioma of the pleura were treated with 4-8 courses of high-dose methotrexate (HDMTX, 3 g total dose) and citrovorum factor rescue. There were 61 male and two female patients of median age 60 years. CT scan was performed before and after treatment and used for response evaluation. Of 60 patients evaluable for response, 37% showed partial or complete remission, 32% showed no change and 32% showed progressive disease. Median survival from start of treatment for all patients was 11 months, for 42 patients with the epithelial type 12 months, and for 20 patients with sarcomatous or mixed types only 5 months. Toxicity was acceptable, with only five patients (8%) terminating therapy due to toxicity. One toxic death occurred. We conclude that HDMTX is an active regimen in malignant pleural mesothelioma. The significantly shorter survival for patients with the sarcomatous or mixed subtypes indicates that further investigations on the activity of HDMTX in mesothelioma should be limited to patients with the epithelial subtype.

In plain English

This was a phase II trial at The Norwegian Radium Hospital testing high-dose methotrexate, a chemotherapy drug, in malignant mesothelioma of the pleura. Of 73 patients admitted from 1984 to 1989, 63 (61 men, two women, median age 60) were reported on. Fifty-nine of the 73 admitted patients (81%) reported some previous asbestos exposure. Planned treatment was four courses of 3 g methotrexate with citrovorum factor rescue, plus four more if patients responded or improved; some had one or two. Response was judged by CT measurement of tumour thickness. Of 60 patients assessed, 37% had partial or complete remission, 32% no change and 32% progressive disease. Median survival from the start of treatment was 11 months overall, 12 months for the 42 epithelial-type patients and 5 months for the 20 with sarcomatous or mixed types, a statistically significant difference. One patient died from toxicity. The authors concluded that the treatment is an active regimen that should possibly be reserved for the epithelial type. They urged caution about the response rate and said randomised studies are needed to show whether it improves survival.

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 phase II treatment trial (chemotherapy study, not an exposure study)
• Who was studied: 63 patients (61 male, 2 female, median age 60) with diffuse malignant mesothelioma of the pleura treated at The Norwegian Radium Hospital, Oslo, from 1984 to 1989, out of 73 such patients admitted in that period
• Exposure: The treatment studied was high-dose methotrexate, 3 g per course, with citrovorum factor rescue. Four courses were planned first, with four more for patients who responded or had no change but felt better. Some patients received only one or two courses. Asbestos exposure was recorded only as background for all 73 admitted patients: 59 (81%) reported some previous exposure and 54% had been repeatedly exposed at work for prolonged periods. By degree of exposure, the counts were heavy 11 (15.1%), moderate 28 (38.4%), slight 20 (27.4%), none 12 (16.4%) and unknown 2 (2.7%). No fiber types were named.
• Main results:
  • Of 60 patients evaluable for response, 37% had partial or complete remission (21 partial, 1 complete), 32% (19) no change and 32% (19) progressive disease
  • Three patients could not be evaluated for response. One died from toxicity during the second course, one had only one course because of toxicity, and one was withdrawn after one course and lost to follow-up.
  • Among responders, median response duration was 7.5 months (range 4 to 70+ months). Median duration of stable disease was 10 months.
  • Median survival from start of treatment was 11 months for all patients, 12 months for the epithelial type (n = 42) and 5 months for sarcomatous or mixed types (n = 20), P = 0.001, log-rank test
  • After 2 years, 32% of patients with the epithelial type were alive, compared with one patient (5%) with the sarcomatous or mixed type
  • No toxicity was recorded in 27 patients (42%). Delayed methotrexate excretion occurred in 6 patients (9%) and led to stopping treatment in 5 of them. One patient died from toxicity.
  • There was no evidence of different response rates between histological subtypes, but the subgroups were too small for such comparisons
• The authors' conclusion: The authors concluded that high-dose methotrexate is an active regimen in malignant pleural mesothelioma. They concluded it is safe with careful monitoring for patients under 80 in fair condition, and that it should possibly be reserved for the epithelial type.
• Limitations the authors state:
  • Subgroups by histological type and stage were too small for comparisons of response rate
  • The response rate should be interpreted with caution because mesothelioma is difficult to evaluate and a new measurement method was used
  • Some patients later received doxorubicin or palliative radiotherapy, and its contribution to survival is unknown
  • The poorer outcome for sarcomatous or mixed types needs verification in more patients. Randomised studies are needed to establish any survival benefit.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Pleura, CT Scan, Median Overall Survival, Pleural Mesothelioma.

Related studies

• High-dose methotrexate in combination with interferons in the treatment of malignant pleural mesothelioma — M. Halme, A. Knuuttila, et al. (1999)
• Despite some expression of folate receptor alpha in human mesothelioma cells, internalization of methotrexate is predominantly carrier mediated — N.Z. Khokhar, A.F. Lam, et al. (2002)
• Combination chemotherapy with mitoxantrone, methotrexate, and mitomycin (MMM regimen) in malignant pleural mesothelioma: a phase II study — C. Pinto, A. Marino, et al. (2001)
• Leucovorin rescue allows effective high-dose pralatrexate treatment and an increase in therapeutic index in mesothelioma xenografts — P.M. Tedeschi, Y.K. Kathari, et al. (2014)
• Computed tomography-guided interstitial high-dose-rate brachytherapy in the local treatment of primary and secondary intrathoracic malignancies — N. Tselis, K. Ferentinos, et al. (2011)
• Epirubicin in malignant mesothelioma: a phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group — K. Mattson, G. Giaccone, et al. (1992)

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