Gemcitabine reverses platinum resistance in platinum-resistant ovarian and peritoneal carcinoma.
Platinum compounds are the key components of chemotherapy for ovarian cancer. Preclinical models in an ovarian cancer cell line (A2780) have demonstrated synergistic activity when gemcitabine is added to cisplatin compared with either single agent alone. Furthermore, the combination leads to increased platinum-adduct retention as a result of decreased DNA repair compared with cisplatin alone. Inhibition of specific exonucleases, such as excision repair cross-complementation group 1 (ERCC1), is integral to the platinum-gemcitabine synergy. In platinum-sensitive recurrent ovarian cancer patients (defined as those patients whose cancer recurs after > 6 months following primary therapy), platinum and gemcitabine have demonstrated an improvement in progression-free survival compared with platinum alone. This is also true for the patients who are only moderately platinum sensitive (defined as those patients who have cancer recurring 6-12 months after primary therapy). Increasing numbers of phase II experiences have demonstrated the activity of the platinum-gemcitabine combination in patients defined as platinum resistant (those with disease progression on therapy or whose disease recurs within 6 months of a platinum-based regimen).
Rose
P G
PG
Department of Obstetrics and Gynecology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. prose@metrohealth.org
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000494:pharmacology; D002986:Clinical Trials as Topic; D004260:DNA Repair; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine