Ranpirnase and its potential for the treatment of unresectable malignant mesothelioma

Figures & data

Figure 1 Anticancer agents usually target either DNA or proteins endowed with receptor and/or signal transduction properties. However, RNA, which is in between DNA and proteins, could also be targeted effectively by specific anticancer drugs such as ranpirnase.

Table 1 Prevalent type of response to ranpirnase observed in established human cancer cell lines in vitro

Human cell line	Author	Prevalent type of response to ranpirnase observed
A549 (NSCLC)	Lee et al 2000	cytotoxic
ASPC-1 (pancreas)
HepG2 (hepatoma)
LS174T (colon)
U937 (lymphoma)	Halicka et al 1996	pro-apoptotic
HL 60 (leukemia)
Colo 320 CM (colon)	Darzynkiewicz et al 1988	cell cycle delay (all phases) or arrest
A-253 (submaxillary carcinoma)
HL 60 (leukemia)
U937 (histocytic lymphoma)	Juan et al 1998	cell cycle arrest in G1

Table 2 In vivo activity of ranpirnase in animal models

Model	Author	Prevalent activity
HT29^MDR1 colon cancer xenograft	Rybak et al 1996	In association with vincristine, ranpirnase overcame MDR1-mediated resistance
M109 Madison mouse carcinoma in mice	Mikulski et al 1990	Ranpirnase slowed tumor growth, increasing survival (in the Madison mouse model)
MDA-MB-231 human breast cancer in nude mice	Mikulski et al1999	Ranpirnase synergized with doxorubicin, increasing survival
Daudi cells given intraperitoneally in SCID mice	Newton et al 2001	Ranpirnase synergized with the anti-CD22 monoclonal antibody epratuzumab, increasing survival
H411E rat hepatoma	Lee et al 2000b	Ranpirnase inhibited tumor growth
MCaIV murine adenocarcinoma
FSaII murine fibrosarcoma
DU145 human prostate cancer in nude mice
AsPC-1 human pancreatic carcinoma in nude mice	Lee et al 2003

Table 3 Results of the first phase III trial of ranpirnase vs doxorubicin in MMe patients according to the patient population considered: ITT (a) or TTG (b) (Vogelzang 2000)

a	Ranpirnase-treated patients	Doxorubicin-treated patients
Median survival	8.4 months	8.2 months
1-year survival rate	33.3%	34.8%
2-year survival rate	13.7%	10.9%
b	Ranpirnase-treated patients	Doxorubicin-treated patients
Median survival	11.6 months	9.6 months
1-year survival rate	46.8%	38.6%
2-year survival rate	20.9%	13.2%

Table 4 Grade III and IV toxicities observed in the phase III study of ranpirnase vs doxorubicin in MMe (according to the National Cancer Institute of Canada [NCIC] classification) (Vogelzang 2000)

	Ranpirnase
	G3		G4
Toxicity	no.	%	no.	%
Asthenia	9	10.8	1	1.2
Arthralgia/myalgia	4	4.8	0	0
Paresthesias	4	4.8	0	0
Dyspnea	4	4.8	0	0
Edema	2	2.4	0	0
Anaphylactoid reaction	0	0	1	1.2
Nausea and vomiting	0	0	1	1.2

	Doxorubicin
	G3		G4
Toxicity	no.	%	no.	%
Asthenia	2	4.5	0	0
Fever	2	4.5	1	2.3
Anorexia	1	2.3	0	0
Mucositis	1	2.3	0	0
Nausea and vomiting	1	2.3	1	2.3