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.

A phase II trial of neoadjuvant doxorrubicin plus gemcitabine, followed by weekly paclitaxel in lo- cally advanced breast cancer: an analysis of effectiveness and toxicity

“…This type of complication had been reported with gemcitabine combinations for neoadjuvant treatment in significantly variable rates (10 to 54%), making some authors to advocate for the use of granulocyte stimulating factor during the AG phase, while others do not [9, 13-15, 18, 19] .In our study, the use of weekly paclitaxel seemed not to have potentiated the neutropenic effect, which was more related to the AG combination, as observed in other studies [14,24,25] . Mucositis was much more frequent in our study than reported in other gemcitabine-combination strategies.…”

Trans-arterial chemoperfusion for the treatment of liver metastases of breast cancer and colorectal cancer: Clinical results in palliative care patients

“…Current therapy regimes are normally based on anthracycline or taxan chemotherapy protocols[ 22 ]. In some combination therapy studies, a median survival time of 10.3-24 mo and a 5-year survival rate of 18% maximum have been attained[ 23 , 24 ].…”

Use of liposomal doxorubicin for adjuvant chemotherapy of breast cancer in clinical practice

“…In this study, adverse reactions of patients mainly included stomatitis, nausea, diarrhea, infection, and constipation, while heart, kidney, lung, or neurotoxicity was not detected. Therefore, NPLD is considered to be able to enter phase-II clinical research in neoadjuvant chemotherapy of breast cancer (Schmid et al, 2005a). In addition, Schmid et al (2005b) found from a phase-II clinical study that a combination of NPLD (60 mg/m 2 ), paclitaxel (75 mg/m 2 ), and gemcitabine (350 mg/m 2 ) in the initial chemotherapy of breast cancer achieved a remission rate of 80% among phases II-III patients, and complete clinical remission was detected in about 25% of patients.…”