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A dose escalation and pharmacokinetic study of biweekly pegylated liposomal doxorubicin, paclitaxel and oxaliplatin in patients with advanced solid tumors

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Abstract

Purpose

To evaluate the maximum tolerated doses (MTD) and the dose-limiting toxicities (DLT) of the combination of pegylated liposomal doxorubicin (PEG-LD), paclitaxel and oxaliplatin (L-OHP) administered every 2 weeks in patients with advanced solid tumors.

Methods

Thirty-nine pretreated patients with advanced solid tumors received escalated doses of PEG-LD (10–16 mg/m2), paclitaxel (100–120 mg/m2) and L-OHP (50–70 mg/m2) every 2 weeks. As one cycle of treatment was considered the administration of both drugs on days 1 and 15 of a 4-week cycle.

Results

The MTDs were PEG-LD 14 mg/m2, paclitaxel 120 mg/m2 and L-OHP 70 mg/m2. Neutropenia was the DLT in all but one case with only one episode of febrile neutropenia and no toxic deaths. Four (4%) and 13 (12%) cycles were complicated by grades 4 and 3 neutropenia, respectively. Grades 2–3 fatigue and neurotoxicity occurred in 13 and 12% of cycles, respectively. Responses were observed in patients with breast, endometrial and ovarian carcinomas.

Conclusions

This is a quite well-tolerated regimen which merits further evaluation in phase II studies.

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Acknowledgments

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

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Authors and Affiliations

  1. Department of Medical Oncology, University General Hospital of Heraklion, PO BOX 1352, 711 10, Heraklion, Crete, Greece

    Kostas Kalbakis, Charalambos Kouroussis, Lambros Vamvakas, Antonia Kalykaki, Nikolaos Vardakis, Vassilis Georgoulias & Dimitris Mavroudis

  2. Department of Pharmacology, School of Medicine, University of Ioannina, Ioannina, Greece

    Periklis Pappas, Martha Nikolaidou & Marios Marselos

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  1. Kostas Kalbakis
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  2. Periklis Pappas
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  9. Vassilis Georgoulias
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  10. Dimitris Mavroudis
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Correspondence to Dimitris Mavroudis.

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Kalbakis, K., Pappas, P., Kouroussis, C. et al. A dose escalation and pharmacokinetic study of biweekly pegylated liposomal doxorubicin, paclitaxel and oxaliplatin in patients with advanced solid tumors. Cancer Chemother Pharmacol 62, 449–456 (2008). https://doi.org/10.1007/s00280-007-0624-3

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  • DOI: https://doi.org/10.1007/s00280-007-0624-3

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