Phase II trial of a single weekly intravenous dose of ranpirnase in patients with unresectable malignant mesothelioma.
OBJECTIVE
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.


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.


CONCLUSIONS
Ranpirnase demonstrated activity and a tolerable toxicity profile in patients with unresectable MM. The prognostic value of the CALGB groups was confirmed.
Mikulski
Stanislaw M
SM
Alfacell Corp, 225 Belleville Ave., Bloomfield, NJ 07003, USA. smikulski@alfacell.com
Costanzi
John J
JJ
Vogelzang
Nicholas J
NJ
McCachren
Spence
S
Taub
Robert N
RN
Chun
Hoo
H
Mittelman
Abraham
A
Panella
Timothy
T
Puccio
Carmelo
C
Fine
Robert
R
Shogen
Kuslima
K
D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012260:Ribonucleases / Q000009:adverse effects / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D015996:Survival Rate
D000970:Antineoplastic Agents; D012260:Ribonucleases; C058703:ranpirnase