Biweekly gemcitabine (GEM) in combination with erlotinib (ERL): an active and convenient regimen for advanced pancreatic cancer.

First Department of Medical Oncology, St. Savvas Anticancer Hospital, Athens, Greece.
Anticancer research (Impact Factor: 1.83). 12/2009; 29(12):5211-7.
Source: PubMed

ABSTRACT Pancreatic cancer remains a disease of high mortality and one of the most frustrating, resistant solid neoplasms to treat. The aim of this study was to evaluate a biweekly gemcitabine plus daily erlotinib regimen in patients with advanced (stage III-IV) pancreatic cancer in terms of overall survival and time to progression of the disease. The secondary aim was to record treatment related toxicities.
Twenty-seven patients with metastatic non-operable pancreatic adenocarcinoma, stage III-IV, consented to receive chemotherapy with gemcitabine and erlotinib. Patients received first-line treatment with gemcitabine (2 g/m(2) via 90 min i.v. infusion every two weeks) and 100 mg erlotinib per os every day, for at least 12 consecutive courses (6 cycles). Treatment was discontinued at disease progression and/or serious toxicity.
The objective response rate was 25.9% (95% confidence interval [CI]: 11.1-46.3%) and the stable disease rate was 59.3% (95% CI: 38.8-77.6%). The one-year overall survival was 20%. The median overall survival and time to progression at the time of assessment was 7.5 months (95% CI: 3.6-42 months) and 5.5 months (95% CI: 1.5-10 months), respectively. Overall survival and time to progression were related to response (p<0.001), while time to progression was further related to disease stage (p=0.011). No grade 4 haematological or non-haematological toxicities were observed.
The biweekly regimen of gemcitabine plus erlotinib has similar toxicity and efficacy to weekly administration, presenting both patients and hospital resource departments with a clearly more convenient therapy alternative.

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    • "Objective response rates were reported in 12 studies [6], [21]–[24], [26], [32]–[37], ranging from 0% to 28.6% with significant between-study heterogeneity (P = 0.003, I2 = 37.8%). The combined objective response rate estimated by the random-effects model was 12.9% (95% CI 9.4%–17.5%) "
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    ABSTRACT: Background This study aims to comprehensively summarize the currently available evidences on the efficacy and safety of gemcitabine plus erlotinib for treating advanced pancreatic cancer. Methodology/Principal Findings PubMed, EMBASE, The Cochrane Library and abstracts of recent major conferences were systematically searched to identify relevant publications. Studies that were conducted in advanced pancreatic cancer patients treated with gemcitabine plus erlotinib (with or without comparison with gemcitabine alone) and reporting objective response rate, disease control rate, progression-free survival, time-to-progression, overall survival, 1-year survival rate and/or adverse events were included. Data on objective response rate, disease control rate, 1-year survival rate and adverse events rate, respectively, were combined mainly by using Meta-Analyst software with a random-effects model. Data on progression-free survival, time-to-progression and overall survival were summarized descriptively. Sixteen studies containing 1,308 advanced pancreatic cancer patients treated with gemcitabine plus erlotinib were included. The reported median progression-free survival (or time-to-progression), median overall survival, 1-year survival rates, objective response rates and disease control rates were 2–9.6 months, 5–12.5 months, 20%–51%, 0%–28.6% and 25.0%–83.3%, respectively. The weighted 1-year survival rate, objective response rate and disease control rate based on studies reporting robust results were 27.9%, 9.1% and 57.0%, respectively. According to the studies with relevant data, the incidences of total and severe adverse events were 96.3% and 62.9%, respectively. The most frequently reported adverse events were leucopenia, rash, diarrhea, vomitting, neutropenia, thrombocytopenia, anaemia, stomatitis, drug-induced liver injury, fatigue and fever. Compared with gemcitabine alone, the progression-free survival and overall survival with gemcitabine plus erlotinib were significantly longer, but there were also more deaths and interstitial lung disease-like syndrome related to this treatment. Conclusions/Significance Gemcitabine plus erlotinib represent a new option for the treatment of advanced pancreatic cancer, with mild but clinically meaningful additive efficacy compared with gemcitabine alone. Its safety profile is generally acceptable, although careful management is needed for some specific adverse events.
    PLoS ONE 03/2013; 8(3):e57528. DOI:10.1371/journal.pone.0057528 · 3.23 Impact Factor
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    ABSTRACT: Preclinical data support further investigation of ascorbic acid in pancreatic cancer. There are currently insufficient safety data in human subjects, particularly when ascorbic acid is combined with chemotherapy. 14 subjects with metastatic stage IV pancreatic cancer were recruited to receive an eight week cycle of intravenous ascorbic acid (three infusions per week), using a dose escalation design, along with standard treatment of gemcitabine and erlotinib. Of 14 recruited subjects enrolled, nine completed the study (three in each dosage tier). There were fifteen non-serious adverse events and eight serious adverse events, all likely related to progression of disease or treatment with gemcitabine or erlotinib. Applying RECIST 1.0 criteria, seven of the nine subjects had stable disease while the other two had progressive disease. These initial safety data do not reveal increased toxicity with the addition of ascorbic acid to gemcitabine and erlotinib in pancreatic cancer patients. This, combined with the observed response to treatment, suggests the need for a phase II study of longer duration. NCT00954525.
    PLoS ONE 01/2012; 7(1):e29794. DOI:10.1371/journal.pone.0029794 · 3.23 Impact Factor
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    ABSTRACT: To investigate the effect of mirtazapine on tumor growth, food intake, body weight, and nutritional status in gemcitabine-induced mild cachexia. Fourteen mice with subcutaneous xenografts of a pancreatic cancer cell line (SW1990) were randomly divided into mirtazapine and control groups. Either mirtazapine (10 mg/kg) or saline solution was orally fed to the mice every day after tumor implantation. A model of mild cachexia was then established in both groups by intraperitoneal injection of gemcitabine (50 mg/kg) 10 d, 13 d, and 16 d after tumor implantation. Tumor size, food intake, body weight, and nutritional status were measured during the experiment. All mice were sacrificed at day 28. (1) After 7 d of gemcitabine administration, body-weight losses of 5%-7% which suggested mild cachexia were measured; (2) No significant difference in tumor size was detected between the mirtazapine and control groups (P > 0.05); and (3) During the entire experimental period, food intake and body weight were slightly greater for the mirtazapine group compared with controls (although these differences were not statistically significant). After 21 d, mice in the mirtazapine group consumed significantly more food than control mice (3.95 ± 0.14 g vs 3.54 ± 0.10 g, P = 0.004). After 25 d, mice in the mirtazapine group were also significantly heavier than control mice (17.24 ± 0.53 g vs 18.05 ± 0.68 g, P = 0.014). Mild cachexia model was successfully established by gemcitabine in pancreatic tumor-bearing mice. Mirtazapine can improve gemcitabine-induced mild cachexia in pancreatic tumor-bearing mice. It was believed to provide a potential therapeutic perspective for further studies on cachexia.
    World Journal of Gastroenterology 06/2012; 18(22):2867-71. DOI:10.3748/wjg.v18.i22.2867 · 2.37 Impact Factor
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