title: Primary chemotherapy with gemcitabine, liposomal doxorubicin and docetaxel in patients with locally advanced breast cancer: results of a phase I trial.
abstract: The primary objective was to determine the optimal doses for gemcitabine (prolonged infusion), liposomal doxorubicin (Myocet) and docetaxel as primary (neoadjuvant) chemotherapy for locally advanced breast cancer. Secondary objectives included evaluation of the safety and efficacy of the regimen. Patients (n=19) with histologically confirmed stage II or III breast cancer were treated with liposomal doxorubicin (50-60 mg/m2) and docetaxel (60-75 mg/m2) on day 1, and gemcitabine as 4-h infusion (350-400 mg/m2) on day 4. Treatment was repeated every 3 weeks for a maximum of 6 cycles. The maximum tolerated doses were gemcitabine 350 mg/m2, liposomal doxorubicin 60 mg/m2 and docetaxel 75 mg/m2. Dose-limiting toxicities were stomatitis, diarrhea and infection. The predominant hematologic toxicity was mild-to-moderate myelosuppression with grade 3/4 neutropenia in 20% of cycles. Non-hematologic toxicity was generally mild, with no grade 4 toxicities being observed. Predominant non-hematologic toxicity was stomatitis, which occurred in 95% of patients. Grade 3 toxicities were reported for stomatitis, nausea, diarrhea, infection and constipation. No cases of cardiac, renal, pulmonary or neurotoxicity were observed. The clinical response rate was 83% and histologically confirmed, clinically complete remissions occurred in two patients (11%). We conclude that the combination of gemcitabine (prolonged infusion), liposomal doxorubicin and docetaxel is safe and highly effective in patients with locally advanced breast cancer as defined by maximum tolerated doses. The evaluated schedule is suitable for phase II studies.
authors.affiliation: Department of Oncology and Hematology, Charité Campus Mitte, Humboldt University Berlin, Berlin. peter.schmid@charite.de
authors.forename: Peter
authors.initials: P
authors.lastname: Schmid
authors.forename: Jutta
authors.initials: J
authors.lastname: Krocker
authors.forename: Carsten-Oliver
authors.initials: CO
authors.lastname: Schulz
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Michniewicz
authors.forename: Annette
authors.initials: A
authors.lastname: Dieing
authors.forename: Holm
authors.initials: H
authors.lastname: Eggemann
authors.forename: Volker
authors.initials: V
authors.lastname: Heilmann
authors.forename: Jens-Uwe
authors.initials: JU
authors.lastname: Blohmer
authors.forename: Orhan
authors.initials: O
authors.lastname: Sezer
authors.forename: Dirk
authors.initials: D
authors.lastname: Elling
authors.forename: Kurt
authors.initials: K
authors.lastname: Possinger
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000473:pathology; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D004317:Doxorubicin; D000093542:Gemcitabine