Phase II study of gemcitabine, doxorubicin and paclitaxel (GAT) as first-line chemotherapy for metastatic breast cancer: a translational research experience

BACKGROUND: Patients with metastatic breast cancer are frequently treated with anthracyclines and taxanes, which are among the most active agents in this disease. Gemcitabine is an interesting candidate for a three-drug combination because of its different mechanism of action and non-overlapping toxicity with respect to the other two drugs. We aimed to evaluate the activity and toxicity of the GAT (gemcitabine, doxorubicin and paclitaxel) regimen, derived from experimental preclinical studies, as first-line chemotherapy in patients with stage IIIB-IV breast cancer. METHODS: Patients with locally advanced or metastatic breast cancer and at least one bidimensionally measurable lesion were included in the present study. Adequate bone marrow reserve, normal cardiac, hepatic and renal function, and an ECOG performance status of 0 to 2 were required. Only prior adjuvant non anthracycline-based chemotherapy was permitted. Treatment consisted of doxorubicin 50 mg/m(2 )on day 1, paclitaxel 160 mg/m(2 )on day 2 and gemcitabine 800 mg/m(2 )on day 6, repeated every 21–28 days. RESULTS: Thirty-three consecutive breast cancer patients were enrolled onto the trial (7 stage IIIB and 26 stage IV). All patients were evaluable for toxicity and 29 were assessable for response. A total of 169 cycles were administered, with a median of 6 cycles per patient (range 1–8 cycles). Complete and partial responses were observed in 6.9% and 48.3% of patients, respectively, for an overall response rate of 55.2%. A response was reported in all metastatic sites, with a median duration of 16.4 months. Median time to progression and overall survival were 10.2 and 36.4 months, respectively. The most important toxicity was hematological, with grade III-IV neutropenia observed in 69% of patients, sometimes requiring the use of granulocyte colony-stimulating factor (27%). Non hematological toxicity was rare and mild. One patient died from sepsis during the first treatment cycle before the administration of gemcitabine. CONCLUSION: The strong synergism among the three drugs found in the preclinical setting was confirmed in terms of both clinical activity and hematological toxicity. Our results seem to indicate that the GAT regimen is effective in anthracycline-naïve metastatic breast cancer and provides a feasible chemotherapeutic option in this clinical setting

Randomized phase II study with two gemcitabine- and docetaxel-based combinations as first-line chemotherapy for metastatic non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Docetaxel and gemcitabine combinations have proven active for the treatment of non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate and compare two treatment schedules, one based on our own preclinical data and the other selected from the literature.</p> <p>Methods</p> <p>Patients with stage IV NSCLC and at least one bidimensionally-measurable lesion were eligible. Adequate bone marrow reserve, normal hepatic and renal function, and an ECOG performance status of 0 to 2 were required. No prior chemotherapy was permitted. Patients were randomized to arm A (docetaxel 70 mg/m²on day 1 and gemcitabine 900 mg/m²on days 3–8, every 3 weeks) or B (gemcitabine 900 mg/m2 on days 1 and 8, and docetaxel 70 mg/m2 on day 8, every 3 weeks).</p> <p>Results</p> <p>The objective response rate was 20% (95% CI:10.0–35.9) and 18% (95% CI:8.6–33.9) in arms A and B, respectively. Disease control rates were very similar (54% in arm A and 53% in arm B). No differences were noted in median survival (32 vs. 33 weeks) or 1-year survival (33% vs. 35%). Toxicity was mild in both treatment arms.</p> <p>Conclusion</p> <p>Our results highlighted acceptable activity and survival outcomes for both experimental and empirical schedules as first-line treatment of NSCLC, suggesting the potential usefulness of drug sequencing based on preclinical models.</p> <p>Trial registration number</p> <p>IOR 162 02</p

PEG Intron in Essential Thrombocythemia: Two Years Treatment in 90 Patients.

In Essential Thrombocythemia (ET) the optimized pharmacokinetics of the weekly-administered pegilated Interferons a (IFN) may increase the patient compliance to a long-lasting IFN treatment. This phase II study has been designed to evaluate in ET patients efficacy, safety and tolerability of a two years treatment with PEG Interferon a - 2b (PEG Intron, Schering-Plough). In 16 Hematological Institutions of the Gruppo Italiano Malattie Mieloproliferative Croniche (GIMMC) the PEG Intron treatment has been started in 90 ET patients, 30 Males and 60 Females, median age 45 years (18-72), previously treated with Alkylating agents (14%), Hydroxyurea (64%), IFN a (31%), Anagrelide (7%) and Antiplatelet drugs (91%). The patients showed: age over 60 (19%), previous thrombosis (4%), disease related symptoms (40%), thrombotic general risk factors (57%), platelet count > 1000 x109/L (81%), peripheral granulocyte precursors (8%), splenomegaly (22%), mean platelet count 1093 x 109/L. In the first year (Part I of the study) the very low initial dose of PEG Intron (25 mg/week) was increased to 50, 75 and 100 mg/week in the patients not reaching the Hematological Response (HR=PLT <500 x109/L) at weeks 13, 26 and 39, respectively. The HR was obtained in 17%, 55%, 79% and 79% of cases after 13, 26, 39 and 52 weeks of treatment, respectively. The PEG Intron toxicity, never of WHO grade IV and only in two cases of grade III, was cause of dose reduction, transitory interruption and drug withdrawal in 7%, 17% and 7% of cases, respectively. Ten patients showed laboratory signs of thyroid dysfunction. Neither thrombotic nor hemorrhagic events were observed. In the second year (Part 2 of the study) 76 responding patients continued PEG Intron treatment at progressively decreasing dose in order to maintain the HR. In detail, the mean PEG Intron dose (mg/week) from the baseline level of 52 was reduced to the values of 33, 34, 30 and 29 at weeks 13, 26, 39 and 52, respectively. In the patients still on PEG Intron treatment at weeks 13, 26, 39 and 52 the rate of the HR was 94.2%, 83.2%, 81.5% and 84.9%, respectively. A withdrawal of PEG Intron was registered after 8-44 weeks (median 23.5) in 10 patients, in 8 of them as consequence of drug related toxicity. The reduction of the PEG Intron dose allowed at week 52 to a significant decrease of the toxicity, respect the baseline. These preliminary data show that PEG Intron at relatively low dose is able to induce and to maintain the HR in the majority of ET patients, with acceptable safety and toxicity

Correction to: Which elderly newly diagnosed glioblastoma patients can benefit from radiotherapy and temozolomide? A PERNO prospective study (Journal of Neuro-Oncology, (2016), 128, 1, (157-162), 10.1007/s11060-016-2093-1)

The members of the PERNO Study Group were not individually captured in the metadata of the original publication. They are included in the metadata of this publication