Emerging drugs for ovarian cancer
- 10 May 2005
- journal article
- review article
- Published by Informa Healthcare in Emerging Drugs
- Vol. 10 (2), 413-424
- https://doi.org/10.1517/14728214.10.2.413
Abstract
Because most patients presenting with advanced ovarian cancer are not curable by surgery alone, chemotherapy represents an essential component of treatment. The disease may be considered as chemosensitive, as in around three-quarters of patients major (complete) responses are seen to initial treatment with the platinum-containing drugs cisplatin and carboplatin either used alone or in combination with the taxane, paclitaxel. However, only 15-20% of patients experience long-term remission as tumours often become resistant. The probability of achieving a second response depends on the duration of remission after first-line therapy: if this is < 6 months (considered as platinum resistant) second responses are uncommon and usually short-lived; if this is > 6, and especially if > 12 months (platinum sensitive), responses may be seen in about a quarter of patients, to the same drugs as used first line or to drugs such as pegylated liposomal doxorubicin, topotecan and hexamethylmelamine (all three are approved in this setting by the FDA). Gemcitabine, oral etoposide, docetaxel and oxaliplatin also show some activity either in sequential addition to existing approved of first-line therapy (as with gemcitabine) or as second-line therapy. However, there is an urgent unmet clinical need for new drugs capable of prolonging survival either by increasing long-term remission rates and/or duration as first-line treatment or to improve on outcomes of second-line treatment. Strategies currently being exploited in clinical trials include attempts to deliver more killing selectively to tumours (e.g., intraperitoneal administration of cisplatin or radiolabelled monoclonal antibodies), agents designed to target drug resistance mechanisms (e.g., TLK-286 activated by glutathione transferase), agents targeting proteins/receptors shown to be selectively expressed in the disease (e.g., monoclonal antibodies recognising CA-125 or HER1; small molecules targeting HER1 such as gefitinib) and disrupting established tumour vasculature (e.g., 5,6-dimethyl xanthenone 4-acetic acid). At the pre-clinical level, agents being developed to target the phosphatidylinositol 3 kinase/AKT/mTOR pathway, and K-Ras inhibitors, may offer efficacy in the future.Keywords
This publication has 55 references indexed in Scilit:
- Randomized, Placebo-Controlled Study of Oregovomab for Consolidation of Clinical Remission in Patients With Advanced Ovarian CancerJournal of Clinical Oncology, 2004
- Reduced expression of MYO18B, a candidate tumor‐suppressor gene on chromosome arm 22q, in ovarian cancerInternational Journal of Cancer, 2004
- Phase II study of gemcitabine and weekly paclitaxel in recurrent platinum-resistant ovarian cancerGynecologic Oncology, 2004
- Mucinous Epithelial Ovarian Cancer: A Separate Entity Requiring Specific TreatmentJournal of Clinical Oncology, 2004
- Ovarian cancer: strategies for overcoming resistance to chemotherapyNature Reviews Cancer, 2003
- Randomized Intergroup Trial of Cisplatin-Paclitaxel Versus Cisplatin-Cyclophosphamide in Women With Advanced Epithelial Ovarian Cancer: Three-Year ResultsJNCI Journal of the National Cancer Institute, 2000
- The Hallmarks of CancerCell, 2000
- A role for methylation of the hMLH1 promoter in loss of hMLH1 expression and drug resistance in ovarian cancerOncogene, 1999
- Cyclophosphamide and Cisplatin Compared with Paclitaxel and Cisplatin in Patients with Stage III and Stage IV Ovarian CancerNew England Journal of Medicine, 1996
- Treatment of relapsed carcinoma of the ovary with cisplatin or carboplatin following initial treatment with these compoundsGynecologic Oncology, 1990