Journal of Clinical Oncology, Vol 20, Issue 1
(January), 2002: 274-281
© 2002 American Society for Clinical Oncology
Phase II Trial of a Single Weekly Intravenous Dose of Ranpirnase in Patients With Unresectable Malignant Mesothelioma
By Stanislaw M. Mikulski,
John J. Costanzi,
Nicholas J. Vogelzang,
Spence McCachren,
Robert N. Taub,
Hoo Chun,
Abraham Mittelman,
Timothy Panella,
Carmelo Puccio,
Robert Fine,
Kuslima Shogen
From the Alfacell Corp, Bloomfield, NJ; Lone Star Oncology, Austin, TX; University of Chicago Cancer Center, Chicago, IL; Thompson Cancer Survival Center, Knoxville, TN; Columbia University, Department of Medical Oncology, New York; and New York Medical College, Valhalla, NY.
Address reprint requests to Stanislaw M. Mikulski, MD, Alfacell Corporation, 225 Belleville Ave, Bloomfield, NJ, 07003; email: smikulski{at}alfacell.com
PURPOSE: A multicenter phase II trial of ranpirnase (Onconase; Alfacell Corp, Bloomfield, NJ) as a single agent was conducted to further assess the safety and clinical efficacy of this novel antitumor ribonuclease. Patients with unresectable and histologically confirmed malignant mesothelioma (MM) were eligible.
PATIENTS AND METHODS: One hundred five patients with Eastern Cooperative Oncology Group performance status 0 to 2 were enrolled onto the study. Thirty-seven percent of patients had not responded to prior chemotherapy. The primary end point of the study was survival. Tumor responses and time to progression were also assessed. The Cancer and Leukemia Group B (CALGB) prognostic group criteria were used to define a treatment target group (TTG). Both the intent-to-treat (ITT) and the TTG populations were analyzed for survival.
RESULTS: Median survival times of 6 months for the ITT and 8.3 months for the TTG populations were observed. The 1- and 2-year survival rates were 34.3% and 21.6% for ITT, respectively, and 42% and 26.8% for TTG, respectively. Among the 81 patients assessable for tumor response, four had partial responses, two had minor regressions, and thirty-five experienced stabilization of previously progressive disease. Patients with responses and stable disease demonstrated markedly prolonged survival. Ranpirnase was well tolerated in the majority of patients, and there were no drug-related deaths.
CONCLUSION: Ranpirnase demonstrated activity and a tolerable toxicity profile in patients with unresectable MM. The prognostic value of the CALGB groups was confirmed.
K.S. is the Chief Executive Officer and S.M. the Excutive Vice President and Medical Director of Alfacell Corporation, of which Onconase is a registered trademark.
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