Back to Search
Start Over
Phase 1 study of the antimesothelin immunotoxin SS1P in combination with pemetrexed and cisplatin for front-line therapy of pleural mesothelioma and correlation of tumor response with serum mesothelin, megakaryocyte potentiating factor, and cancer antigen 125.
- Source :
-
Cancer [Cancer] 2014 Nov 01; Vol. 120 (21), pp. 3311-9. Date of Electronic Publication: 2014 Jul 02. - Publication Year :
- 2014
-
Abstract
- Background: The primary objective of this study was to determine the safety and maximum tolerated dose (MTD) of the antimesothelin immunotoxin SS1(dsFv)PE38 (SS1P) (a recombinant antimesothelin immunotoxin consisting of a murine antimesothelin variable antibody fragment [Fv] linked to PE38, a truncated portion of Pseudomonas exotoxin A) in combination with pemetrexed and cisplatin in chemotherapy-naive patients with advanced malignant pleural mesothelioma (MPM). Secondary objectives included tumor response, SS1P pharmacokinetics, and serum biomarkers of response.<br />Methods: Chemotherapy-naive patients with stage III or IV, unresectable, epithelial or biphasic MPM and normal organ functions were eligible. Pemetrexed (500 mg/m(2) on day 1) and cisplatin (75 mg/m(2) on day 1) were administered every 3 weeks for up to 6 cycles with escalating doses of SS1P administered intravenously on days 1, 3, and 5 during cycles 1 and 2. Tumor response was evaluated every 6 weeks.<br />Results: Twenty-four patients received SS1P at 4 dose levels from 25 to 55 mcg/kg. Grade 3 fatigue was dose-limiting in 1 patient at 55 mcg/kg. The MTD of SS1P was established as 45 mcg/kg. Other grade 3 toxicities associated with SS1P included hypoalbuminemia (21%), back pain (13%), and hypotension (8%). Of 20 evaluable patients, 12 (60%) had a partial response, 3 had stable disease, and 5 had progressive disease. Of 13 patients who received the MTD, 10 (77%) had a partial response, 1 had stable disease, and 2 had progressive disease. Objective radiologic responses were associated with significant decreases in serum mesothelin (P=.0030), megakaryocyte potentiating factor (P=.0005), and cancer antigen 125 (Pā<ā.0001).<br />Conclusions: SS1P given with pemetrexed and cisplatin is safe and well tolerated and exhibits significant antitumor activity in patients with unresectable, advanced pleural mesothelioma. Serum mesothelin, megakaryocyte potentiating factor, and cancer antigen 125 levels correlated with objective tumor responses.<br /> (Published 2014. This article is a U.S. Government work and is in the public domain in the USA.)
- Subjects :
- ADP Ribose Transferases
Aged
Antibodies, Monoclonal blood
Bacterial Toxins
CA-125 Antigen blood
Cisplatin administration & dosage
Exotoxins
Female
GPI-Linked Proteins administration & dosage
GPI-Linked Proteins blood
Guanine administration & dosage
Humans
Lung Neoplasms blood
Lung Neoplasms pathology
Male
Maximum Tolerated Dose
Mesothelin
Mesothelioma blood
Mesothelioma pathology
Mesothelioma, Malignant
Middle Aged
Neoplasm Staging
Pemetrexed
Pleural Neoplasms blood
Pleural Neoplasms pathology
Virulence Factors
Pseudomonas aeruginosa Exotoxin A
Antibodies, Monoclonal administration & dosage
Antineoplastic Combined Chemotherapy Protocols administration & dosage
Glutamates administration & dosage
Guanine analogs & derivatives
Lung Neoplasms drug therapy
Mesothelioma drug therapy
Pleural Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1097-0142
- Volume :
- 120
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 24989332
- Full Text :
- https://doi.org/10.1002/cncr.28875