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A dose escalation and pharmacokinetic study of the biweekly administration of paclitaxel, gemcitabine and oxaliplatin in patients with advanced solid tumors

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Abstract

Purpose

To determine the dose-limiting toxicities (DLTs) and the maximum tolerated doses (MTDs) of the paclitaxel, gemcitabine, oxaliplatin combination administered biweekly in patients with advanced solid tumors.

Patients and methods

Patients received escalated doses of paclitaxel (starting dose: 100 mg/m2), gemcitabine (starting dose: 800 mg/m2) and oxaliplatin (starting dose: 50 mg/m2) on days 1 and 15 in cycles of every 4 weeks. DLTs were evaluated during the first cycle.

Results

Twenty-seven patients (median age 65 years) with performance status 0–1 were treated on six dose escalation levels. Eleven patients (40.7%) were chemotherapy naïve, six (22.2%) had received 1 prior chemotherapy regimen and ten (37.1%) 2 or more. The DLT level was reached at the doses of paclitaxel 110 mg/m2, gemcitabine 1,150 mg/m2 and LOHP 70 mg/m2. The dose-limiting events were grade 4 neutropenia and grade 3 febrile neutropenia. Neutropenia was the most common adverse event. A median of 3 cycles per patient was administered. One complete and five partial responses were observed in patients with ovarian carcinoma, NSCLC, urothelial cancer, mesothelioma and cancer of unknown primary. No pharmacokinetic drug interactions were detected.

Conclusions

The recommended doses for future phase II studies of this combination are paclitaxel 110 mg/m2, gemcitabine 1,000 mg/m2 and oxaliplatin 70 mg/m2 every 2 weeks. The regimen is generally well tolerated and merits further evaluation.

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Acknowledgments

This work was partly supported by a research grant from the Cretan Association for Biomedical Research (CABR).

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Authors and Affiliations

  1. Department of Medical Oncology, University Hospital of Heraklion, 71110, Heraklion, Crete, Greece

    Zacharenia Saridaki, John Souglakos, Nikolaos Vardakis, Athanasios Kotsakis, Vassilis Georgoulias & Dimitris Mavroudis

  2. Department of Pharmacology, Medical School, University of Ioannina, 45110, Ioannina, Greece

    Periklis Pappas, Martha Nikolaidou & Marios Marselos

Authors
  1. Zacharenia Saridaki
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  2. Periklis Pappas
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  3. John Souglakos
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  4. Martha Nikolaidou
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  5. Nikolaos Vardakis
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  6. Athanasios Kotsakis
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  7. Marios Marselos
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  8. Vassilis Georgoulias
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  9. Dimitris Mavroudis
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Correspondence to Dimitris Mavroudis.

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Saridaki, Z., Pappas, P., Souglakos, J. et al. A dose escalation and pharmacokinetic study of the biweekly administration of paclitaxel, gemcitabine and oxaliplatin in patients with advanced solid tumors. Cancer Chemother Pharmacol 65, 121–128 (2009). https://doi.org/10.1007/s00280-009-1013-x

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  • DOI: https://doi.org/10.1007/s00280-009-1013-x

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