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

Steven Attia; Sherry Morgan-Meadows; 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

doi:10.1007/s00280-008-0844-1

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

Steven Attia, Sherry Morgan-Meadows, 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

Hematology / Oncology / Cancer Center / Breast Clinic

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

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.

Original language	English (US)
Pages (from-to)	45-51
Number of pages	7
Journal	Cancer chemotherapy and pharmacology
Volume	64
Issue number	1
DOIs	https://doi.org/10.1007/s00280-008-0844-1
State	Published - Jun 2009

Keywords

Capecitabine
Fixed-dose rate
Gemcitabine
Phase I

ASJC Scopus subject areas

Oncology
Toxicology
Pharmacology
Cancer Research
Pharmacology (medical)

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Attia, S., Morgan-Meadows, S., Holen, K. D., Bailey, H. H., Eickhoff, J. C., Schelman, W. R., Traynor, A. M., Mulkerin, D. L., Campbell, T. C., McFarland, T. A., Huie, M. S., Cleary, J. F., Tevaarwerk, A. J., Alberti, D. B., Wilding, G., & Liu, G. (2009). Dose-escalation study of fixed-dose rate gemcitabine combined with capecitabine in advanced solid malignancies. Cancer chemotherapy and pharmacology, 64(1), 45-51. https://doi.org/10.1007/s00280-008-0844-1

Dose-escalation study of fixed-dose rate gemcitabine combined with capecitabine in advanced solid malignancies. / Attia, Steven; Morgan-Meadows, Sherry; Holen, Kyle D.; Bailey, Howard H.; Eickhoff, Jens C.; Schelman, William R.; Traynor, Anne M.; Mulkerin, Daniel L.; Campbell, Toby C.; McFarland, Thomas A.; Huie, Michael S.; Cleary, James F.; Tevaarwerk, Amye J.; Alberti, Dona B.; Wilding, George; Liu, Glenn.

In: Cancer chemotherapy and pharmacology, Vol. 64, No. 1, 06.2009, p. 45-51.

Research output: Contribution to journal › Article › peer-review

Attia, S, Morgan-Meadows, S, Holen, KD, Bailey, HH, Eickhoff, JC, Schelman, WR, Traynor, AM, Mulkerin, DL, Campbell, TC, McFarland, TA, Huie, MS, Cleary, JF, Tevaarwerk, AJ, Alberti, DB, Wilding, G & Liu, G 2009, 'Dose-escalation study of fixed-dose rate gemcitabine combined with capecitabine in advanced solid malignancies', Cancer chemotherapy and pharmacology, vol. 64, no. 1, pp. 45-51. https://doi.org/10.1007/s00280-008-0844-1

Attia, Steven ; Morgan-Meadows, Sherry ; Holen, Kyle D. ; Bailey, Howard H. ; Eickhoff, Jens C. ; Schelman, William R. ; Traynor, Anne M. ; Mulkerin, Daniel L. ; Campbell, Toby C. ; McFarland, Thomas A. ; Huie, Michael S. ; Cleary, James F. ; Tevaarwerk, Amye J. ; Alberti, Dona B. ; Wilding, George ; Liu, Glenn. / Dose-escalation study of fixed-dose rate gemcitabine combined with capecitabine in advanced solid malignancies. In: Cancer chemotherapy and pharmacology. 2009 ; Vol. 64, No. 1. pp. 45-51.

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

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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note = "Funding Information: 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).",

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T1 - Dose-escalation study of fixed-dose rate gemcitabine combined with capecitabine in advanced solid malignancies

AU - Attia, Steven

AU - Morgan-Meadows, Sherry

AU - Holen, Kyle D.

AU - Bailey, Howard H.

AU - Eickhoff, Jens C.

AU - Schelman, William R.

AU - Traynor, Anne M.

AU - Mulkerin, Daniel L.

AU - Campbell, Toby C.

AU - McFarland, Thomas A.

AU - Huie, Michael S.

AU - Cleary, James F.

AU - Tevaarwerk, Amye J.

AU - Alberti, Dona B.

AU - Wilding, George

AU - Liu, Glenn

N1 - Funding Information: 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).

PY - 2009/6

Y1 - 2009/6

N2 - 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.

AB - 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.

KW - Capecitabine

KW - Fixed-dose rate

KW - Gemcitabine

KW - Phase I

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