Ruxandra Irimia, Ioana Teodora Tofolean, Roxana Gabriela Sandu, Oana Elena Băran, Maria Cătălina Ceauşescu, Vlad Coşoreanu, Maria Teodora Ilie, Ramona Babeş, Constanţa Ganea and Irina Băran
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Hend Ahmed El-Hadaad, Hanan Ahmed Wahba and Hayam Fathy Abd-El Hay Ghazy
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Renata Rezonja, Lea Knez, Tanja Cufer and Aleš Mrhar
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16. Slevin ML
Renata Rezonja Kukec, Iztok Grabnar, Tomaz Vovk, Ales Mrhar, Viljem Kovac and Tanja Cufer
Background. Chemotherapy with platinum agent and etoposide for small-cell lung cancer (SCLC) is supposed to be associated with intermediate risk (10-20%) of febrile neutropenia. Primary prophylaxis with granulocyte colonystimulating factors (G-CSFs) is not routinely recommended by the treatment guidelines. However, in clinical practice febrile neutropenia is often observed with standard etoposide/platinum regimen. The aim of this analysis was to evaluate the frequency of neutropenia and febrile neutropenia in advanced SCLC patients in the first cycle of standard chemotherapy. Furthermore, we explored the association between severe neutropenia and etoposide peak plasma levels in the same patients.
Methods. The case series based analysis of 17 patients with advanced SCLC treated with standard platinum/etoposide chemotherapy, already included in the pharmacokinetics study with etoposide, was performed. Grade 3/4 neutropenia and febrile neutropenia, observed after the first cycle are reported. The neutrophil counts were determined on day one of the second cycle unless symptoms potentially related to neutropenia occurred. Adverse events were classified according to Common Toxicity Criteria 4.0. Additionally, association between severe neutropenia and etoposide peak plasma concentrations, which were measured in the scope of pharmacokinetic study, was explored.
Results. Two out of 17 patients received primary GCS-F prophylaxis. In 15 patient who did not receive primary prophylaxis the rates of both grade 3/4 neutropenia and febrile neutropenia were high (8/15 (53.3%) and 2/15 (13.3%), respectively), already in the first cycle of chemotherapy. One patient died due to febrile neutropenia related pneumonia. Neutropenic events are assumed to be related to increased etoposide plasma concentrations after a standard etoposide and cisplatin dose. While the mean etoposide peak plasma concentration in the first cycle of chemotherapy was 17.6 mg/l, the highest levels of 27.07 and 27.49 mg/l were determined in two patients with febrile neutropenia.
Conclusions. Our study indicates that there is a need to reduce the risk of neutropenic events in chemotherapy treated advanced SCLC, starting in the first cycle. Mandatory use of primary G-CSF prophylaxis might be considered. Alternatively, use of improved risk models for identification of patients with increased risk for neutropenia and individualization of primary prophylaxis based on not only clinical characteristics but also on etoposide plasma concentration measurement, could be a new, promising options that deserves further evaluation.
Nina Erculj, Barbara Faganel Kotnik, Marusa Debeljak, Janez Jazbec and Vita Dolzan
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Robert Königsberg, Julia Maierhofer, Tanja Steininger, Gabriele Kienzer and Christian Dittrich
chemotherapy plus trastuzumab plus bevacizumab. Available at http://clinicaltrials.gov/ct2/show/NCT00625898?term=BETH&rank=1
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Ciardiello F, Cervantes A, Vega-Villegas ME, Casado E, Rodriguez-Braun E, Martinelli E., et al. Optimal dose for an every 2 week (q2w) cetuximab (C) regimen in patients (pts) metastatic colorectal cancer (mCRC): a phase I safety, pharmacokinetics(PK) and pharmacodynamics (PD) study of weekly (q1w) add q2w schedules. [Abstract]. Eur J Cancer 2007; 5(4): 247.
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