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The Therapeutic Options in Platinum-Resistant Ovarian Cancer

October-December 2007, Volume 02, Number 4
Ángel J. Lacave, Paula J. Fonseca, Guillermo Crespo and Noemí Villanueva
Medical Oncology Service, Hospital Universitario Central de Asturias, Oviedo, Spain

Patients with advanced ovarian cancer who fail to respond to first-line therapy or who relapse within the first six months, that is, platinum-resistant patients, have a poor prognosis. Prospective, randomized phase III studies in secondline therapy have demonstrated that pegylated liposomal doxorubicin, topotecan, and gemcitabine appear to have similar activity in platinumresistant patients. These validated drugs achieve a response rate of approximately 15% in these patients, depending on the predictive factor of response. At present, pegylated liposomal doxorubicin constitutes the reference treatment, given its good therapeutic index. After having revisited all the therapeutic agents classically included in the list of active drugs in second-line chemotherapy for ovarian cancer, we have found that in phase II trials, only etoposide and hexamethylmelamine have demonstrated similar activity to the validated drugs in platinum-resistant patients, so they could be a treatment option when these validated drugs have failed. Carboplatin can be another treatment alternative, mainly when the disease-free interval is close to six months since it does not appear to lose activity despite non-platinum pretreatment. Weekly paclitaxel has shown good activity in platinum/paclitaxelresistant ovarian cancer and can also be contemplated in this scenario. In patients in whom chemotherapy is not indicated or in whom other drugs have failed, antihormone treatment can be considered. Of all the antihormone therapeutic agents available, the ones that have proven greatest efficacy are tamoxifen (20 mg twice daily) and letrozole. Although the clinical trials performed until now are not robust enough to propose estrogen receptors as a predictive factor for response, it seems that tumors with a high level of estrogen receptors (e.g. more than 100 fmoles/mg) are those that present a greater probability of response at least with letrozole. The most promising investigational new drugs are bevacizumab, epothilones, and oregovomab. Ongoing phase III preliminary data with these drugs are hopeful and could involve a step forward in the treatment of platinum-resistant ovarian cancer.

Key words:
Platinum-resistant. Platinum-refractory. Recurrent ovarian cancer. Relapsed ovarian cancer. Second-line chemotherapy. Ovarian cancer.
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