Gemcitabine and vinorelbine in pemetrexed-pretreated patients with malignant pleural mesothelioma

Department of Medical Oncology and Hematology, Humanitas Clinical Institute of Rozzano, Milan, Italy.
Cancer (Impact Factor: 4.89). 04/2008; 112(7):1555-61. DOI: 10.1002/cncr.23337
Source: PubMed


Pemetrexed-cisplatin chemotherapy is the standard of care in the first-line treatment of unresectable malignant pleural mesothelioma (MPM). Second-line cytotoxic therapy is considered for a growing group of patients, but the optimal treatment has not been defined to date. Gemcitabine and vinorelbine have shown activity in the first-line setting. The objective of this study was to evaluate the activity and toxicity of the gemcitabine-vinorelbine combination in pemetrexed-pretreated patients with MPM.
From January 2004 to September 2006, 30 consecutive patients who were pretreated with pemetrexed with or without a platinum-derivative were enrolled. Gemcitabine 1000 mg/m(2) and vinorelbine 25 mg/m(2) were administered intravenously on Days 1 and 8 every 3 weeks. Treatment was repeated for a maximum of 6 cycles or until progression or unacceptable toxicity.
A partial response was observed in 3 patients (10%; 95% confidence interval [CI], 2.1-26.5%), and 10 patients (33.3%; 95% CI, 17.3-52.8%) had stable disease after treatment. Overall, 13 patients (43.3%; 95% CI, 25.5-62.6%) achieved disease control. The median time to progression was 2.8 months (range, 0.6-12.1 months), and the median survival was 10.9 months (range, 0.8-25.3 months). Hematologic toxicity was acceptable, with grade 3 or 4 neutropenia occurring in 11% of patients and thrombocytopenia occurring in 4% of patients; no case of febrile neutropenia was observed. Nonhematologic toxicity generally was mild.
The gemcitabine and vinorelbine combination was moderately active and had an acceptable toxicity profile in pemetrexed-pretreated patients with MPM. The role of second-line treatment in MPM needs to be evaluated in prospective trials in large series of patients who are stratified according to previous treatment and prognostic factors.

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Available from: Federico Cappuzzo, Jan 15, 2015
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    • "Gemcitabine is a polar deoxycytidine analogue. It can inhibit both DNA synthesis and ribonucleotide reductase [1] [2] [3] [4] [5] [6]. "
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    ABSTRACT: Gemcitabine (GEM), acyclovir, and 5-fluorouracil are synthetic nucleoside analogues. These drugs function by inhibiting both RNA and DNA synthesizes. In this study, we investigated the inhibition effects of these drugs (gemcitabine hydrochloride, acyclovir, and 5-fluorouracil) on hPON1 enzyme activity from human serum in vitro conditions. IC50 values for gemcitabine hydrochloride, acyclovir, and 5-fluorouracil were determined to be 26.610 mM, 255.885 mM, and 564.334 mM, respectively. hPON1 enzyme was purified from human serum using ammonium sulphate precipitation, DEAE-Sephadex A-50 ion-exchange chromatography and Sephadex G-200 gel-filtration chromatography. It was purified approximately 231 fold with 34.2% yield. For purity determination of the enzyme SDS polyacrylamide gel electrophoresis was used and molecular mass was approximately determined 43 kDa by this method.
    The Open Biochemistry Journal 05/2014; 1(1):15-24. DOI:10.15764/BIOC.2014.01002
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    • "Another target of gemcitabine is the enzyme ribonucleotide reductase (Table 1). Gemcitabine and the vinca-derived vinorelbine, which have shown activity as the first-line setting, have been recently also investigated in association with the objective of evaluating their activity and toxicity in pemetrexed (a new generation antifolate)-pretreated hMPM patients: the combination was only moderately active showing an acceptable toxicity profile (Zucali et al., 2008). "
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    ABSTRACT: Malignant pleural mesothelioma is a neoplasm characterized by an increasing incidence and poor prognosis. When surgical treatment cannot be performed, systemic chemotherapy remains the main therapeutic option. Here we report the case of a 41-year-old female patient with epithelioid malignant pleural mesothelioma who was treated with carboplatin and pemetrexed despite her critical condition. She showed an impressive response to this first-line chemotherapy and, after disease progression, to further chemotherapy with gemcitabine and vinorelbine. She is still alive, with unexpectedly long-lasting survival.
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