High-dose methotrexate in combination with interferons in the treatment of malignant pleural mesothelioma

Abstract

Summary Twenty six patients with pleural mesothelioma of UICC stage I-IV excluding M1 disease (46% of whom had stage I disease and 38% stage III disease) were treated intravenously with high dose MTX (3 g) and calcium folinate rescue three times at intervals of 2 weeks and three times at intervals of 3 weeks. Natural interferon (IFN)-α (3 MIU days 2-10) and recombinant IFN-γ 1b (50 µg m -2 on days 2, 6 and 10) were injected subcutaneously after each MTX dose. At the end of MTX treatment the IFNs were continued as maintenance therapy until disease progression. Seven partial responses were observed among 24 patients evaluable for response (response rate 29%, 95% confidence interval 13-51%). Median duration of response was 10 months (range 3-24 months). Median survival was 17 months and 1-year and 2-year survival rates 62% and 31% respectively. The toxicity of the chemo-immunotherapy was acceptable. Treatment was stopped in one patient who developed grade IV neurological toxicity. MTX dose reductions were rare (two patients with grade 1-2 renal toxicity). The combination of high dose MTX and IFN-α and IFN-γ is active against malignant pleural mesothelioma and well-tolerated. The survival rates are encouraging.

The Use of Chemotherapy in Patients with Advanced Malignant Pleural Mesothelioma: A Systematic Review and Practice Guideline

“…Of the relevant studies retrieved (Table 1), eight were randomized trials 10 -17 and the remainder were noncomparative studies: 55 regimens (reported in 52 articles) focused on nonplatinum-based, single-agent chemotherapy 18 -69 ; 12 researched non-platinum-based combination chemotherapy 70 -81 ; 35 concentrated on platinum-based chemotherapy ; and 12 investigated chemotherapy and immunotherapy. [117][118][119][120][121][122][123][124][125][126][127][128] No evidence-based clinical practice guidelines for the treatment of mesothelioma were identified, although in 2001 the British Thoracic Society published a statement intended to guide the management of malignant mesothelioma. 129 The statement was developed through a review of literature and expert consensus; however, a comprehensive and systematic review of the literature was not attempted, and the British Thoracic Society indicated that limitations on the quality of evidence did not allow for the development of recommendations.…”

Successful Treatment With Novel Triple Drug Combination Consisting of Interferon-γ, Interferon Alfacon-1, and Ribavirin in a Nonresponder HCV Patient to Pegylated Interferon Therapy

“…No significant, unexpected adverse events were noted; there was an acceptable safety and tolerability profile in this group of patients. Beside hepatitis B, the experience with combination therapy with interferon-α and interferon-γ is in oncologic conditions, where significant, unexpected toxicities have not been seen (10)(11)(12)(13)(14).…”

Malignant Pleural Mesothelioma: From the Bench to the Bedside

“…Seven (29%) had a PR, and the 1- and 2-year survival rates were 62 and 31%, respectively [144]. A small study of epirubicin plus IL-2 showed only 1 PR among 25 patients with advanced disease [145].…”