A phase II evaluation of ifosfamide and mesna in unresectable diffuse malignant mesothelioma: A southwest oncology group study

Abstract

Background. Malignant mesothelioma is a highly treatment‐resistant neoplasm. This study represents an attempt to define an effective form of systemic therapy. Methods. Twenty‐six patients with unresectable diffuse malignant mesothelioma were enrolled in Southwest Oncology Group (SWOG) study 8731 and treated with ifosfamide, 2 g/m2 intravenously for 4 days, and mesna 2 g/m2 intravenously for 5 days, every 3 weeks. Patients were either previously untreated with chemotherapy or had at most one prior systemic treatment. Results. Two patients, or 8% (95% confidence interval, 1‐25%), achieved partial response, with response durations of 4 and 6 months. One additional patient met criteria for tumor size reduction but not duration criteria. Thirteen (50%) patients had stable disease of 4 months' median duration (range, 1‐13 months). The median survival of the entire group was 6.5 months. The dose‐limiting toxicity was granulocytopenia (11 patients, ≤ 250/μl). Conclusions. Ifosfamide/mesna has modest activity in malignant mesothelioma. It could be tested using alternate dosage schedules and in combination with other agents in treating this highly resistant neoplasm.

Aggregation‐Induced Emission and Efficient Solid‐State Fluorescence from Tetraphenylethene‐Based N,C‐Chelate Four‐Coordinate Organoborons

“…Grade 4 hematologic toxicity was reported to occur in 24 patients (63%), and nonhematologic toxicity was reported to occur in 7 patients (18%). Therefore, our current results are similar to the 8% response rate observed in our prior SWOG study (8731), which was associated with a 42% incidence of Grade 4 hematologic toxicity,17 and a European study of ifosfamide that reported 1 partial response among 40 eligible patients, with significant hematologic toxicity 25…”

“…Interest in ifosfamide has reemerged because of its use with the uroprotector 2‐mercaptoethane sodium sulfonate (mesna). Ifosfamide has been reported to have antitumor activity at standard doses in patients with soft tissue sarcoma and osteogenic sarcomas,14–16 and was studied in malignant mesothelioma patients in a prior Southwestern Oncology Group (SWOG) study (SWOG‐8731) 17. There was a reported response rate of 8% (two partial responses).…”

Malignant Pleural Mesothelioma and the Role of Non– Operative Therapies

“…In general, the single agent studies have been hard pressed to obtain response rates of over 20% and complete responses were rare. Of the single agent chemotherapy trials, many agents such as the vinca alkaloids (with the exception of vinorelbine) had no efficacy, and responders were few for the alkylating agents [126] [127] [128] [129]. The three classes of agents which showed some degree of response, albeit with response rates that rarely exceeded 20%, were the anthracyclines, platinum compounds and the antimetabolites/antifolates [130].…”

Current concepts in chemotherapy for malignant pleural mesothelioma

“…With respect to alkylating agents, cyclophosphamide appears to be without activity (1), while varying results have been obtained with ifosfamide, with RRs ranging from 3% to 24% (19–21). Also, mitomycin C may possess activity (22).…”