BJ,
I hadn't seen that Trp-p8 work - looks pretty interesting.
I really haven't seen anything dramatic for PC on the horizon. DNA (again!) has something interesting with a Herceptin-like drug (abstract below), but it's still very early. Glivec in PC was a disappointment (reported at ASCO).
MEDI has MDX-070 in a Phase I - this is an anti-PSMA antibody that looks interesting. (I think I recall this discussed at the MEDI analyst day webcast, but I'm not sure). Vitaxin (also MEDI) sounds promising for bone mets.
Satraplatin (SPPI is the US play here - see abstract below) looks like a modest improvement for hormone refractory treatment, but generally things still seem very grim once PC is hormone refractory.
I don't follow the area that closely (give me a few more years and I'll likely start to pay much more attention <g>), so I could well have missed some interesting developments.
Here is a list of all targeted therapeutics in development:
hemonctoday.com
and these are all cancer therapeutics in development:
hemonctoday.com
Scanning both of them, there are a fair number of new prostate drugs in development I've never heard of. But overall I'm surprised prostate isn't more of a focus (seems like that male-dominated scientific/pharma establishment is not quite living up to its biases <g>)
Here are two abstracts:
Clinical activity in a phase I trial of HER-2-targeted rhuMAb 2C4 (pertuzumab) in patients with advanced solid malignancies (AST)
Year:
2003
Printable Version
Category:
Receptor-Targeted Antibodies/Ligands
Abstract No:
771
Author(s):
D. B. Agus, M. Gordon, C. Taylor, R. B. Natale, B. Karlan, D. Mendelson, S. Kelsey, G. Fyfe; Cedars-Sinai Medical Center, Los Angeles, CA; Arizona Cancer Ctr, Phoenix, AZ; Arizona Cancer Ctr, Tucson, AZ; Genentech Inc, South San Francisco, CA
Abstract:
RhuMAb 2C4 (2C4) is a humanized HER2 antibody that binds to an epitope distinct from trastuzumab (Herceptin). 2C4 blocks ligand-associated heterodimerization of HER2 with other HER-kinase family members [HER1 (EGFR), HER3, and HER4] and thereby inhibiting intracellular signaling through MAP kinase and PI3 kinase. Anti-tumor activity has been seen in tumor xenograft models, including HER2 non-overexpressing(0+/1+) as well as overexpressing tumors (2+/3+). 21 patients (12 female, 9 male) with AST received IV 2C4 every 3 weeks at one of the following dose levels: 0.5mg/kg (n=3), 2mg/kg (n=3), 5mg/kg (n=4), 10mg/kg (n=3), 15mg/kg (n=8). 19 patients completed a minimum of 2 cycles. Median age was 57 yrs, median ECOG PS was 1. Cancer types included breast (n=3), prostate (n=5), NSCLC (n=4), ovarian (n=3), colon (n=2), liposarcoma (n=1), pancreatic (n=2; 1 adenocarcinoma, 1 islet cell), and unknown primary (n=1). The majority of adverse events (AEs) reported were grade 1 or 2. Most frequently reported AEs to date were nausea (48%), vomiting (52%), fatigue (43%), diarrhea (33%), rash (38%), abdominal pain (33%) and anemia (38%). 24 events were graded 3 or 4; with two of these events felt to be possibly drug-related: a GI bleed (in a patient with pre-existing esophageal varices) and a patient with left ventricular failure following a myocardial infarction. Patients were closely monitored with 2-D echos and serologic cardiac markers and there was no other evidence of cardiac dysfunction observed. The pharmacokinetics of 2C4 were similar to other humanized IgG antibodies with a terminal half-life of ~3 weeks. Modeling of steady state trough plasma concentrations at all dose levels over 0.5mg/kg exceeded those required for anti-tumor activity in animal models (20ug/ml). Three patients (14%) achieved PRs: ovarian cancer (5mg/kg); prostate cancer (15mg/kg) and islet cell carcinoma (15mg/kg). Two remain on therapy at 44.6wks and 30.6wks. An additional 8 patients (38%) had SD after 2 cycles, persisting for a median of 13.7 weeks (range 6.1 - 24.4). We conclude that 2C4 is well tolerated at doses up to 15mg/kg q3wk. Clinical activity was observed.
-------
IRVINE, Calif., June 3, 2003 ? Spectrum Pharmaceuticals, Inc. (Nasdaq: SPPI ? News) today announced the presentation of positive clinical data on its lead compound, satraplatin, at the Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago. The study, entitled, ?Randomized phase III trial of a new oral platinum, satraplatin (JM-216) plus prednisone or prednisone alone in patients with hormone refractory prostate cancer,? (Abstract #1586) was presented by Cora N. Sternberg, M.D., FACP, Chief of the Department of Medical Oncology at the San Camillo and Forlanini Hospitals, Rome, Italy and Head of the Genitourinary Tract Group for the European Organization for the Research and Treatment of Cancer (EORTC). The study results demonstrated statistically significant superiority of the satraplatin arm (p=0.023) in time to disease progression, with doubling of progression-free survival.
The study involved 50 randomized patients and evaluated satraplatin plus prednisone (N=27) versus prednisone alone (N=23) for use as a first-line chemotherapy treatment in hormone-refractory prostate cancer (HRPC). Prednisone is a synthetic hormone often used in treating advanced prostate cancer. Compliance to treatment and tolerance were excellent in the study. Patients were followed until progression or death.
The study results showed that satraplatin treatment significantly lengthened the time to disease progression (p=0.023): the median time to disease progression was 5.2 months for satraplatin versus 2.5 months for the control arm. Additionally, at six months, 41% of patients treated in the satraplatin arm were progression free versus 22% of patients in the control arm. A greater than 50% decline in PSA (prostate-specific antigen) was experienced by 33% (9/27) of patients in the satraplatin arm versus 9% (2/23) of patients in the control arm. The median overall survival time was 15 months for patients treated in the satraplatin arm versus 12 months for patients in the control arm. At one year, 70 percent of the patients treated in the satraplatin arm were still alive, versus only 48 percent of the patients in the control arm.
Peter |
