Clin Cancer Res
-
Randomized Controlled Trial Clinical Trial
Approval summary for zoledronic acid for treatment of multiple myeloma and cancer bone metastases.
This article summarizes data submitted to the United States Food and Drug Administration for marketing approval of zoledronic acid (Zol; Novartis Pharmaceuticals, East Hanover, NJ), a bisphosphonate drug for treating patients with bone metastases. ⋯ In prostate cancer, both the proportions analysis and time-to-SRE analysis showed significantly less bone morbidity on Zol (4 mg) than placebo, but no significant difference between Zol (8 mg) and placebo in either analysis. In the solid tumor study, the time to SRE analysis but not the proportions analysis showed significantly less skeletal morbidity on Zol (4 mg) than placebo, and Zol (8 mg) was significantly better than placebo in both analyses. The breast cancer and myeloma study demonstrated noninferiority of Zol compared with Pam, with Zol retaining at least 49.3% of the Pam treatment effect previously demonstrated in placebo-controlled trials. Zol was approved on February 22, 2002, by the United States Food and Drug Administration for the "treatment of patients with multiple myeloma and documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy." The recommended dose and schedule is 4 mg of Zol infused over 15 min every 3-4 weeks. Increased Zol doses and shorter infusions are not recommended because of potential renal toxicity.
-
In Phase I, the purpose was to determine the maximum tolerated dose and pharmacokinetics of docetaxel plus cyclophosphamide (DC) with and without granulocyte colony-stimulating factor in the treatment of patients with solid tumors. For Phase II, the purpose was to determine the safety and efficacy of this combination as first-line treatment in patients with metastatic breast cancer (MBC). ⋯ DC combination therapy is an active regimen with acceptable toxicity and is appropriate regardless of prior anthracycline therapy. In view of the high activity and lack of cardiotoxicity, this combination warrants additional investigation in early stage breast cancer and in combination with trastuzumab.
-
Epithelial cell adhesion molecule (Ep-CAM) is a tumor-associated antigen overexpressed in many solid tumors but shows limited expression in normal epithelial tissues. To exploit this favorable expression pattern for targeted cancer therapy, an Ep-CAM-specific recombinant immunotoxin was developed and its antitumor activity investigated. ⋯ We describe for the first time the development of a fully recombinant Ep-CAM-specific immunotoxin and demonstrate its potent activity against solid tumors of various histological origins. 4D5MOCB-ETA is currently being evaluated in a Phase I study in patients with refractory squamous cell carcinoma of the head and neck.
-
Randomized Controlled Trial Clinical Trial
Approval summary: imatinib mesylate capsules for treatment of adult patients with newly diagnosed philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase.
The purpose is to describe the Food and Drug Administration (FDA) review and approval of imatinib (Gleevec; Novartis Pharmaceuticals, East Hanover, NJ) for treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myelogenous leukemia (CML) in chronic phase. ⋯ On December 20, 2002, imatinib was granted accelerated approval under subpart H, rather than regular approval. Follow-up is short compared with the natural history of chronic phase CML or more mature results with established therapies such as IFN-alpha or transplantation. If imatinib should stop working after 1.5-2 years, the results could be importantly different from the present analysis. As a Phase IV postmarketing commitment, the applicant has agreed to provide follow-up reports on this imatinib study annually for the next 6 years.
-
We investigated the potential of cyclooxygenase (COX)-2 as anappropriate chemopreventive and/or therapeutic target for oral cancer. ⋯ NS398 inhibits the growth of OSCC cells by mechanisms that are dependent and independent of suppression of PGE(2) synthesis. Molecular targeting of COX-2, PGE(2) synthase, or PGE(2) receptors may be useful as a chemopreventive or therapeutic strategy for oral cancer.