| Abstract: |
G-3139 is an antisense phosphorothioate oligodeoxynucleotide (AS PS ON) which suppresses bcl-2 expression and is being developed by Genta Inc for the potential treatment of various cancers [308375]. G-3139 is in various stages of phase I/IIa trials. One study, initiated in May 1999, at the Lombardi Cancer Center at Georgetown University Medical Center, US, will examine G- 3139 in conjunction with docetaxel. In a phase I/IIa dose-escalating trial to treat non-Hodgkin's lymphoma (NHL), at the Royal Marsden NHS Trust, UK, no serious, clearly drug-attributable or dose-limiting adverse effects were noted and in some patients encouraging signs of potential drug activity were observed. The responses included one patient in whom cancer mass was reduced and one who developed a complete response for over 38 weeks in duration [239159,291608,325262]. A new phase II protocol using G-3139 combined with standard chemotherapies in relapsed NHL patients has also begun [325262]. Other phase I/IIa studies include: the safety and efficacy of G-3139 in the treatment of hormone-resistant, metastatic prostate cancer, when administered with mitoxantrone [305822]; the treatment of relapsed follicular NHL, when administered with cyclophosphamide [311217]; the treatment of Stage III and IV metastatic malignant melanoma in combination with dacarbazine [289755]; the treatment of hormone-resistant, metastatic prostate cancer when administered over a significantly longer duration than studied previously and in combination with an androgen-receptor blocking agent [291608 ]. The National Cancer Institute (NCI) funded and conducted preclinical studies of G-3139 in July 1996 and in June 1998, the NCI and Genta entered into a Cooperative Research and Development Agreement (CRADA) for the development of G3139 [290153]. Clinical trials, focusing on colorectal cancer, small cell lung cancer and leukemia, were underway as of April 1999. The company licensed the rights for the use of bcl-2 as a target for antisense and gene therapy-based treatments from the University of Pennsylvania. In June 1998, Genta received two patents relating to its antisense compounds [289685]. |
| Keywords: |
cancer chemotherapy; treatment outcome; clinical trial; drug activity; drug tolerability; review; drug efficacy; drug safety; nonhuman; united states; skin manifestation; paclitaxel; neoplasms; animals; mice; dacarbazine; melanoma; phase 2 clinical trial; antineoplastic combined chemotherapy protocols; neoplasm proteins; inflammation; cyclophosphamide; antineoplastic activity; drug screening; structure-activity relationship; mice, inbred balb c; docetaxel; prostate cancer; nonhodgkin lymphoma; drug distribution; rna, messenger; mitoxantrone; androgen antagonists; gene therapy; drug clearance; cancer care facilities; safety; taxoids; phase 1 clinical trial; antineoplastic agents, hormonal; rna, neoplasm; oblimersen; proto-oncogene proteins c-bcl-2; national institutes of health (u.s.); intravenous drug administration; drug elimination; clinical trials, phase ii; clinical trials, phase i; genes, bcl-2; thionucleotides; patents; cancer; humans; human; male; female
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