Health and Prostate

Overview. A vast amount of R&D has been committed to the study of epidermal growth factor receptor (EGFR) inhibition. Although several EGFR inhibitors have been launched for other solid tumor types, results for CaP have been very disappointing. The two main approaches researchers have investigated are the specific inhibition of EGFR tyrosine kinase (e.g., gefitinib [AstraZeneca's Iressa]) and MAbs directed at the external domain of the EGFR (e.g., trastuzumab [Genen-tech / Roche's Herceptin] and, initially, panitumumab). Both approaches have failed to deliver results in CaP. The following sections discuss only trastuzumab and gefitinib because of their success in treating other tumor types. Please note that Panitumumab, has now been discontinued. One agent targeting the EGFR pathway that is in earlier-stage development is pertuzumab (Genentech / Roche / Chugai's Omnitarg). This next-generation, humanized, anti-HER / neu MAb is in Phase II development. Enrollment for the trial, which recruited men with hormone-refractory CaP who had received a taxane or epothilone, has been completed. Read more [...]

Overview. Despite its promise, no antisense therapy for the treatment of cancer has yet been approved. Genta (in collaboration with Sanofi-Aventis) and Isis are the main players in antisense approaches. This section focuses on Genta's agent, oblimersen (Genasense), because it has been the most extensively investigated for CaP. Another antisense oligonucleotide in development is Lorus Therapeutics' GTI-2501, which is targeted to the Rl component of ribonucleotide reductase, a highly regulated enzyme in the cell cycle of mammalian cells that plays an essential role in DNA synthesis and cell proliferation. The lack of published data precludes further discussion of it. Antisense oligonucleotides are short sequences of single-stranded DNA that can bind to a specific region of corresponding messenger RNA (mRNA) sequence, thereby blocking both the expression and translation of the mRNA itself and the generation of the corresponding protein encoded by the mRNA. In this way, antisense molecules can block the expression of undesirable genes and their proteins. Mechanism of Action. Oblimersen. Read more [...]

Cell Genesys's GVAX vaccine for CaP consists of tumor cells that have been irradiated and genetically modified to secrete GM-CSF, a hormone that plays a key role in stimulating the body's immune response. Unlike Provenge, the vaccine is not patient-specific and is administered by intradermal injection, making it significantly more convenient to deliver and less expensive to manufacture. GVAX has completed a Phase II trial, and the first of two planned Phase III trials among patients with metastatic, hormone-refractory CaP is ongoing. The ongoing Phase III trial (Vaccine ImmunoTherapy with Allogeneic CaP Cell Lines [VITAL-1]) aims to enroll 600 chemotherapy-naive, asymptomatic patients and will compare GVAX vaccine with taxane chemotherapy to determine the survival benefit. Patients will receive intradermal injections of the vaccine every two weeks for up to six months. The second trial (VITAL-2) will enroll symptomatic patients and compare the effect of GVAX vaccine plus taxane chemotherapy with that of taxane monotherapy on palliation of bone pain. Both trials will enroll patients at all levels Read more [...]

Satraplatin (GPC Biotech's JM-216) is a third-generation oral platinum agent. Satraplatin reentered Phase III development for second-line treatment of hormone-refractory CaP in September 2003; a previous Phase III trial was halted early by the previous developer, Bristol-Myers Squibb. The ongoing Phase III trial, whose primary endpoint is time to disease progression, is known as SPARC (Satraplatin and Prednisone Against Refractory Cancer). In 2003, the FDA granted satraplatin fast-track status, and in early 2004, the Phase III trial was extended to Europe. A Phase I study protocol that will combine satraplatin with docetaxel to treat various tumor types is in preparation. Because satraplatin is orally administered and does not require hydration to prevent renal toxicity, home administration is possible. In animal models, satraplatin has demonstrated efficacy in tumors that are resistant to platinum agents, possibly as a result of increased lipophilicity, allowing for more passive uptake of the platinum complexes by cancer cells. At ASCO 2003, investigators presented findings from the first Read more [...]