Gemcitabine, anthracycline, and taxane combinations for advanced breast cancer.
In patients with advanced breast cancer, treatment with paclitaxel and doxorubicin has been shown to produce impressive overall response rates (up to 94%) and to prolong overall survival significantly over a combination of fluorouracil (5-FU), doxorubicin, and cyclophosphamide (Cytoxan, Neosar) in one prospective phase III clinical study. These results have been challenged, however, by other data demonstrating no survival advantage for taxane-based therapies. In addition, the combination of paclitaxel and doxorubicin has repeatedly been shown to be complicated by the development of treatment-related congestive heart failure, when cumulative doxorubicin doses exceed 300-360 mg/m2. Consequently, attempts have been made to increase the complete remission rate and overall survival resulting from first-line treatment of metastatic breast cancer without compromising patient safety. Gemcitabine (Gemzar)--a relatively effective, well-tolerated and partially non-cross-resistant antitumor compound with limited toxicity--represents an attractive alternative to paclitaxel/anthracycline combinations. Initial studies of combination therapy with gemcitabine and paclitaxel have produced an average response rate of 52%, with time to progression ranging between 7.0 and 14.5 months. Three-drug regimens containing gemcitabine, an anthracycline, and paclitaxel have been tested in phase II studies and have produced impressive response rates of 82.9% with gemcitabine, doxorubicin, and paclitaxel and 92% with gemcitabine, epirubicin (Ellence), and paclitaxel (GET). The Central European Cooperative Oncology Group has evaluated the GET regimen vs a regimen containing 5-FU, epirubicin, and cyclophosphamide (FEC) in a randomized, prospective phase III study. Interim toxicity analysis showed that the GET regimen was well tolerated but produced more grade 4 neutropenia (64% vs 42%, P = .084) and significantly more grade 4 thrombocytopenia (12% vs 0%; P < .001) than FEC. Anaphylactic/allergic reactions, peripheral polyneuropathy, nausea, and cardiotoxicity constituted rare events and did not exceed grade 1 or 2 in severity. Although final data from this phase III trial are not yet available, preliminary analysis suggests the GET regimen represents an attractive option for patients with advanced breast cancer.
Zielinski
Christoph C
CC
Clinical Division of Oncology, Department of Medicine I, University Hospital, Central European Cooperative Oncology Group (CECOG), Vienna, Austria. christoph.zielinski@akh-wien.ac.at
D000293:Adolescent; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000008:administration & dosage*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003841:Deoxycytidine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012720:Severity of Illness Index; D043823:Taxoids / Q000008:administration & dosage*; D000093542:Gemcitabine
D018943:Anthracyclines; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D043823:Taxoids; D003841:Deoxycytidine; C080625:taxane; D000093542:Gemcitabine