Pancreatic cancer - Palliative therapy: Chemotherapy

The Chinese-German Journal of Clinical Oncology 04/2007; 6(2):142-148. DOI: 10.1007/s10330-007-0042-3


Single-agent Gemcitabine has been the standard treatment for advanced pancreatic adenocarcinoma in the past years. Due to
the aggressive and often chemotherapy-refractory character of this malignancy, systemic treatment options still remain limited.
Many combination therapies have been evaluated in clinical trials to improve survival over Gemcitabine alone, until recently
without satisfying results. Based on the positive results of a recent randomized trial, the combination of Gemcitabine and
Capecitabine might become a new standard as first-line treatment for advanced pancreatic cancer. The clinical advantage of
Erlotinib as a novel targeted agent in combination with Gemcitabine seems to be only marginal. Due to the small number of
studies, there is still no standard of care in second-line therapy, but Oxaliplatin seems to be an active treatment option
in Gemcitabine refractory disease. This article will review the development of cytotoxic antitumoral treatment for advanced
pancreatic adenocarcinoma (locally advanced, irresectable and/or metastatic disease) including monotherapies and newer approaches
with combination therapies.

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    ABSTRACT: To conduct a randomized phase II trial of dose-intense gemcitabine using a standard 30-minute infusion or the fixed dose rate (FDR) infusion (10 mg/m2/min) in patients with pancreatic adenocarcinoma. In this prospective trial, patients with locally advanced and metastatic pancreatic adenocarcinoma were treated with 2,200 mg/m2 gemcitabine over 30 minutes (standard arm) or 1,500 mg/m2 gemcitabine over 150 minutes (FDR arm) on days 1, 8, and 15 of every 4-week cycle. The primary end point of this trial was time to treatment failure. Secondary end points included time to progression, median survival, safety, and pharmacokinetic studies of gemcitabine. Ninety-two patients were enrolled onto this study; 91% of the patients had metastatic disease. Time to treatment failure was comparable in both treatment groups; however, the median survival for all patients was 5.0 months in the standard arm and 8.0 months in the FDR arm (P =.013). For patients with metastases, the median survival was 4.9 months in the standard arm and 7.3 months in FDR arm (P =.094). The 1- and 2-year survival rates for all patients were 9% (standard arm) versus 28.8% (FDR; P =.014) and 2.2% (standard arm) versus 18.3% (FDR; P =.007), respectively. Patients in the FDR infusion arm experienced consistently more hematologic toxicity. Pharmacokinetic analyses demonstrated a two-fold increase in intracellular gemcitabine triphosphate concentration in the FDR arm (P =.046). Pharmacokinetic and clinical data in this trial supports the continued evaluation of the FDR infusion strategy with gemcitabine.
    Journal of Clinical Oncology 10/2003; 21(18):3402-8. DOI:10.1200/JCO.2003.09.140 · 18.43 Impact Factor
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    ABSTRACT: Pancreatic carcinoma is considered among the most chemoresistant of human malignancies. The most commonly used cytotoxic single agents, 5-fluorouracil and 2'-deoxy-2',2'-difluorocytidine (gemcitabine), have objective response rates of less than 10% in large studies. Hypothesizing noncross resistance and a synergistic interaction between gemcitabine and cisplatin, early clinical studies have demonstrated significant activity with this combination in patients with several types of malignant disease. A Phase II study was undertaken to determine the efficacy of gemcitabine in combination with cisplatin in patients with locally advanced and metastatic pancreatic carcinoma based on these considerations. The eligibility criteria included histologically confirmed, locally advanced, unresectable or metastatic exocrine carcinoma of the pancreas with no prior gemcitabine therapy; prior adjuvant therapy was allowed provided the last day of therapy was at least 6 months prior to starting treatment; clinically measurable or evaluable disease; a Southwest Oncology Group scale performance status of 0-2; a life expectancy of > 12 weeks; and adequate bone marrow, hepatic, and renal function. A total of 42 patients, 4 patients with locally advanced, unresectable disease and 38 patients with metastatic disease, were treated and received a total of 211 cycles of therapy between May 1997 to March 1999. The median age of patients was 61.5 years. The patients were treated in the outpatient setting with a combination of gemcitabine 1,000 mg/M(2) intravenously over 30 minutes administered on Days 1, 8, and 15 of each cycle and cisplatin 50 mg/M(2) intravenously administered after gemcitabine infusion on Days 1 and 15 with adequate prehydration accompanied by adequate urinary output. Cycles were repeated every 28 days. Response and toxicity were assessed according to World Health Organization and standard criteria. The complete and partial response rate among all 42 registered patients was 11 of 42 patients (26%; 95% confidence interval, 0.14-0.42). Stabilization of disease was seen in 15 patients (38%). Two additional patients with metastatic disease who achieved major responses to chemotherapy were rendered free of disease surgically, achieving a complete response status. The median overall survival was 7.1 months (95% confidence interval [CI], 6.3-9.1 months), with 64% of patients alive at 6 months and 19% of patients alive at 12 months. The median time to disease progression was 5.4 months (range, 0.9-20.8 months). Major toxicities were neutropenia and thrombocytopenia, with one episode of neutropenic fever. The combination of gemcitabine and cisplatin appeared to have significantly greater activity than single-agent gemcitabine in this Phase II study, with tolerable toxicity. The antitumor activity of this combination needs to be confirmed in multi-institutional or comparative trials.
    Cancer 08/2001; 92(3):569-77. · 4.89 Impact Factor
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    ABSTRACT: In this study, we estimated the response rate, duration of response, and type, severity and reversibility of toxicities in patients with Stage IV adenocarcinoma of the pancreas treated with docetaxel. Twenty-one patients with locally advanced or metastatic pancreatic cancer, previously untreated or treated with surgery or radiation alone, were treated with 100 mg/m2 docetaxel as a 1 hr infusion once every 21 days. All the patients were pretreated with dexamethasone and diphenhydramine. Twenty patients were assessable for both response and toxicity. One patient was assessable for toxicity alone. However, all the patients were assessed for survival. The major side effect of the drug was neutropenia, which required a dose reduction to 75 mg/m2 in approximately half of the patients. Nine patients were hospitalized with neutropenic fever. Fluid retention was not a significant problem. One patient had a partial response lasting for 21 weeks and 7 patients had stable disease. The remaining patients had progressive disease. The median survival for all the patients was 5.9 months. Docetaxel as a single agent showed limited activity against adenocarcinoma of the pancreas. Since the completion of this study, molecular predictors of in vitro response to docetaxel have been described. Confirmation of the clinical relevance of such predictors in humans could allow for the identification of a subgroup of patients with a higher rate of response to docetaxel.
    Cancer Investigation 02/2002; 20(4):464-72. DOI:10.1081/CNV-120002146 · 2.22 Impact Factor
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