Randomized comparison of cyclophosphamide, imidazole carboxamide, and adriamycin versus cyclophosphamide and adriamycin in patients with advanced stage malignant mesothelioma: a Sarcoma Intergroup Study.

Abstract

In 1980, a consensus chemotherapy intergroup study for advanced malignant mesothelioma was initiated based on a collaborative agreement among the Eastern Cooperative Oncology Group (ECOG), the Southwest Oncology Group (SWOG), and the Southeastern Cancer Study Group (SECSG). The purpose of the study was to evaluate cyclophosphamide (500 mg/m2 day 1), imidazole carboxamide (250 mg/m2 days 1 through 5), and doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) (50 mg/m2 day 1) v cyclophosphamide (500 mg/m2) and doxorubicin (50 mg/m2) in a randomized prospective clinical trial involving 76 fully evaluable patients with advanced stages II to IV malignant mesothelioma. A total of nine responses (12%) were documented, including three complete and six partial responses. There was no significant difference in response duration or survival between treatment arms. Leukopenia (greater than 2,000/microL) was observed in 46% of patients treated with the three-drug combination and 38% of patients receiving the two-drug combination. The variables of performance status 0-1 and the absence of prior chemotherapy/radiotherapy were significant with respect to favorable impact on survival. We conclude, based on the minimal benefit observed, that the combination of cyclophosphamide and doxorubicin with or without imidazole carboxamide does not warrant further investigation in patients with advanced-stage malignant mesothelioma.

Chemotherapy for malignant pleural mesothelioma: past results and recent developments

“…A multi -institutional randomised study was designed to compare the activity of doxorubicin-cyclophosphamide with a triplet consisting of these agents in addition to dacarbazine. With a response rate of 13%, the triplet did not prove superior to the doublet (RR: 11%) (Samson et al, 1987).…”

Novel systemic therapy against malignant pleural mesothelioma

“…In the late 1980's and 1990's, randomized trials evaluated the efficacy of multiple single-agent chemotherapeutics including anthracyclines, topoisomerase inhibitors, taxanes, alkylating agents, and platinum analogues in MPM with low response rates of 0-13%, progression free survival of 2-5 months, and median overall survival ranging 5-8 months (39)(40)(41)(42)(43) (36,44).…”

Osteopontin-mediated enhanced hyaluronan binding induces multidrug resistance in mesothelioma cells

“…As a result, chemotherapy is still the mainstay of disease therapy. Various drugs including doxorubicin, cyclophosphamide, cisplatin (CDDP), carboplatin, gemcitabine (GEM), and pemetrexed have been tested in different combinations (Samson et al, 1987;Chahinian et al, 1993;White et al, 2000;Kindler et al, 2001;Hughes et al, 2002). However, the limited combinations of these agents have marginally provided some clinical benefit because of multidrug resistance.…”