The role of gemcitabine-based doublets in the management of ovarian carcinoma.
Efforts to improve further therapy for advanced ovarian carcinoma currently focus on addition of a third active agent to front-line chemotherapy. Three agents with activity against disease clinically resistant to paclitaxel and the platinum compounds are of greatest interest: gemcitabine, topotecan, and liposome-encapsulated doxorubicin. Three strategies to add a third agent include a triplet regimen that adds a third agent concurrently; a sequential doublet regimen giving three to four cycles of the new agent plus a platinum followed by three to four cycles of paclitaxel plus a platinum; and sequential single agents consisting of three to four cycles of the new agent with three to four cycles each of paclitaxel and a platinum. Gemcitabine in combination with another agent has been evaluated to develop doublet regimens for the second of these three strategies. Combinations both feasible and active include gemcitabine plus cisplatin or carboplatin, gemcitabine plus paclitaxel, gemcitabine plus topotecan, gemcitabine plus liposome-encapsulated doxorubicin, gemcitabine plus vinorelbine, and gemcitabine plus treosulfan. The combinations of gemcitabine plus a platinum compound appear most promising with synergism suggested by the data. A gemcitabine/carboplatin doublet for four cycles followed by four cycles of paclitaxel/carboplatin is currently under evaluation in a randomized phase III trial (Gynecologic Oncology Group [GOG] protocol 0182).
Thigpen
Tate
T
Division of Oncology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA. jtthigpen@worldnet.att.net
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016190:Carboplatin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D002986:Clinical Trials as Topic; D003841:Deoxycytidine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D019772:Topotecan / Q000008:administration & dosage; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077235:Vinorelbine; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D014747:Vinblastine; D005047:Etoposide; D019772:Topotecan; D004317:Doxorubicin; D016190:Carboplatin; C018404:treosulfan; D002066:Busulfan; D017239:Paclitaxel; D002945:Cisplatin; D000077235:Vinorelbine; D000093542:Gemcitabine