[Anthracyclines in therapy of ovarian carcinoma: a systematic review of primary and 2nd-line therapy after platinum].
Despite being the subject of clinical research for more than 20 years, the role of anthracyclines in the treatment of ovarian cancer is still undefined. This review summarizes and re-evaluates the published data with the anthracylines doxorubicin, epirubicin (4'-epi-doxorubicin), daunorubicin (idarubicin), aclarubicin, and pirarubicin. The studies were identified by MEDLINE-search and analysis of the references cited in the identified articles and reviews covering this subject. First-line therapy: Studies from the 70ies could demonstrate that doxorubicin was as effective as alkylating agents. The combination of anthracylines and alkylating agents provided superior results compared with alkylating agents alone. Further improvements were gained by the introduction of platinum-anthracyline combination regimens. Doxorubicin and epirubicin showed comparable activity when combined with platinum. The comparison between platinum-anthracyline containing combination regimens with platinum based regimens without anthracylines did not provide definitive answers. The majority of studies (with relatively small patient numbers) did not reveal any significant benefit for the anthracyline containing regimens. In contrast, four meta-analyses combining several studies showed a significant improvement when anthracylines were added to platinum based regimens. This question came up again when standard treatment for ovarian cancer was modified by the introduction of paclitaxel in the mid 90ies. Currently, two randomized large intergroup trials evaluate the role of anthracyclines in combination with platinum and paclitaxel. Results from these studies will be available in 1-2 years and might help to describe the role for anthracyclines in ovarian cancer treatment more precisely. Until then, the use of anthracyclines in upfront chemotherapy of ovarian cancer outside of clinical trials cannot be recommended. 2n-line therapy: The anthracyclines doxorubicin and epirubicin are among the most active single agents for the treatment of platinum refractory ovarian cancer. Both agents achieved tumor responses in up to 25%. Preliminary data suggest, that the combination with paclitaxel could increase efficacy. No such effect was reported for any other combination. In contrast, single agent anthracyclines cannot be recommended for treatment of platinum sensitive tumors. However, combining anthracyclines with platinum resulted in remarkable response rates of more than 50% of patients with platinum sensitive tumors. Only few studies report the use of anthracylines after platinum and paclitaxel containing first-line chemotherapy. Preliminary data from small studies (40 patients) suggest that anthracyclines showed activity in this particular population. No final conclusions can be drawn. There is a need for developing effective 2nd-line therapies for patients failing platinum and paclitaxel combination regimens. Among others, anthracyclines should be evaluated in this clinical setting.
du Bois
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Klinik für Gynäkologie & gynäkologische Onkologie, Dr.-Horst-Schmidt-Kliniken Wiesbaden. AGO.OVAR.SEKR@UUMAIL.DE
Lück
H J
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Pfisterer
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Meier
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Bauknecht
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D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate
D000903:Antibiotics, Antineoplastic; D009944:Organoplatinum Compounds
Anthrazykline in der Therapie des Ovarialkarzinoms: eine systematische Ubersicht zur Primär- und 2nd-line-Therapie nach Platin.