Nonpegylated liposomal doxorubicin (TLC-D99), paclitaxel, and trastuzumab in HER-2-overexpressing breast cancer: a multicenter phase I/II study.

PURPOSE: To determine the recommended dose, cardiac safety, and antitumor activity of nonpegylated liposomal doxorubicin (TLC-D99), paclitaxel, and the anti-HER-2 monoclonal antibody trastuzumab in patients with HER-2-overexpressing locally advanced nonoperable breast cancer (LABC) and metastatic breast cancer (MBC). EXPERIMENTAL DESIGN: Women with measurable, previously untreated, HER-2-overexpressing LABC and MBC with a baseline left ventricular ejection fraction (LVEF) >50% received weekly trastuzumab in combination with escalating doses of weekly paclitaxel and TLC-D99 every 3 weeks for 6 cycles. LVEF monitoring was done every 3 weeks for the first 18 weeks and every 8 weeks thereafter. RESULTS: Sixty-nine patients participated, 15 in the dose escalating part and 54 at the recommended phase II dose (28 patients with LABC and 26 patients with MBC). The recommended doses of TLC-D99 and paclitaxel were 50 mg/m(2) every 3 weeks and 80 mg/m(2)/wk, respectively. Twelve (17%) patients developed asymptomatic declines in LVEF. In 8 of these patients, LVEF recovered to >or=50% after a median time of 9 weeks (range, 3-38 weeks). In the rest of patients, LVEF ranged from 44% to 49%. No patients developed symptomatic cardiac heart failure. The overall response rate was 98.1% (95% confidence interval, 90.1-99.9) with a median time to progression not reached in LABC and of 22.1 months (95% confidence interval, 16.4-46.3) in MBC patients. CONCLUSIONS: Nonpegylated doxorubicin, paclitaxel, and trastuzumab combination is safe, does not result in clinically manifest cardiac toxicity, and has a high rate of durable responses in HER-2-overexpressing breast cancer patients. Further exploration of this combination is warranted.

Incidence of hand-foot syndrome with capecitabine in combination with chemotherapy as first-line treatment in patients with advanced and/or metastatic gastric cancer suitable for treatment with a fluoropyrimidine-based regimen.

INTRODUCTION: Hand-foot syndrome (HFS) is a limiting toxicity of capecitabine, which is not life-threatening but could compromise capecitabine efficacy. MATERIALS AND METHODS: This phase II, multicenter, non-controlled study assessed the safety, particularly grade three HFS incidence, and efficacy of four capecitabine-based chemotherapy regimens [cisplatin/capecitabine (CX), epirubicin/cisplatin/capecitabine (ECX), epirubicin/oxaliplatin/capecitabine (EOX) and docetaxel/cisplatin/capecitabine (DCX)] as first-line treatment for advanced and/or metastatic gastric cancer. RESULTS: One hundred and eight patients were assigned to one of the four treatment groups, according to investigator's criteria, and grouped together for both safety and efficacy primary analyses. HFS was reported in 31 patients (19.6%) and its first presentation occurred at a median of 72 days (range 19-209 days). Grade 3 HFS developed in 6.3, 5.2, 3.7 and 2.4%, of patients receiving ECX, DCX, EOX or CX chemotherapy regimen, respectively. Capecitabine dose reduction/discontinuation due to HFS was required in 5.7% of patients (9/158). The most common (> 10%) grade 3-4 treatment-related AEs were neutropenia (15.2%), asthenia (12.0%) and diarrhoea (11.4%). CONCLUSIONS: A moderate incidence of HFS was reported in patients treated with capecitabine, which generally presented late and required dose reduction in < 1/3 of patients. The results suggest that capecitabine may be useful in combination with standard fluorouracil-based regimens in patients with advanced and/or metastatic gastric cancer with favourable safety profile.