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Dose-escalation study of fixed-dose rate gemcitabine combined with capecitabine in advanced solid malignancies

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Abstract

Purpose

To define dose limiting toxicities (DLTs) and the maximum tolerated dose (MTD) of capecitabine with fixed-dose rate (FDR) gemcitabine.

Methods

Eligible adults (advanced solid tumor; performance status ≤2) received capecitabine 500 mg/m2 PO BID days 1–14 and FDR gemcitabine (400–1,000 mg/m2 escalated by 200 mg/m2 increments) at 10 mg/m2/min days 1 and 8 on a 21-day cycle. A traditional 3 + 3 cohort design was used to determine the MTD.

Results

Thirty patients (median age 59 years) were enrolled. The predominant grade ≥3 toxicity was myelosuppression, particularly neutropenia. At dose level 4 (1,000 mg/m2 gemcitabine), two out of five evaluable patients had a DLT (grade 4 neutropenia ≥7 days). At dose level 3 (800 mg/m2 gemcitabine), one patient had a DLT (grade 3 neutropenia ≥7 days) among six evaluable patients. Therefore, the MTD and recommended phase II dose was designated as capecitabine 500 mg/m2 PO BID days 1–14 with 800 mg/m2 FDR gemcitabine days 1 and 8 infused at 10 mg/m2 per min on a 21-day cycle. Partial responses occurred in pretreated patients with esophageal, renal cell and bladder carcinomas.

Conclusions

This regimen was well tolerated and may deserve evaluation in advanced gastrointestinal and genitourinary carcinomas.

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Acknowledgments

We thank our patients and their families for their participation in this study. We thank the nurses and research specialists of the University of Wisconsin Phase I Program for their devotion to these patients and this study. The study was partially supported by Roche. We acknowledge support from National Institutes of Health grant T32 CA009614 Physician Scientist Training in Cancer Medicine (Dr. Attia).

Disclosures

None.

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Authors and Affiliations

  1. University of Wisconsin Paul P. Carbone Comprehensive Cancer Center Madison, 600 Highland Avenue, Box 5669, Madison, WI, 53792, USA

    Steven Attia, Kyle D. Holen, Howard H. Bailey, Jens C. Eickhoff, William R. Schelman, Anne M. Traynor, Daniel L. Mulkerin, Toby C. Campbell, Thomas A. McFarland, Michael S. Huie, James F. Cleary, Amye J. Tevaarwerk, Dona B. Alberti, George Wilding & Glenn Liu

  2. Gulf Coast Minority-Based Clinical Oncology Program, Mobile, AL, 36607, USA

    Sherry Morgan-Meadows

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  1. Steven Attia
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  16. Glenn Liu
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Corresponding author

Correspondence to Glenn Liu.

Additional information

The results of this research appeared as abstract ID 13509 at the 2008 American Association of Clinical Oncology meeting in Chicago, IL, USA.

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Attia, S., Morgan-Meadows, S., Holen, K.D. et al. Dose-escalation study of fixed-dose rate gemcitabine combined with capecitabine in advanced solid malignancies. Cancer Chemother Pharmacol 64, 45–51 (2009). https://doi.org/10.1007/s00280-008-0844-1

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  • DOI: https://doi.org/10.1007/s00280-008-0844-1

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