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 | |
| State | Published - Jun 2009 |
| Externally published | Yes |
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Keywords
- Capecitabine
- Fixed-dose rate
- Gemcitabine
- Phase I
ASJC Scopus subject areas
- Cancer Research
- Oncology
- Pharmacology
- Pharmacology (medical)
- Toxicology
Cite this
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
}
TY - JOUR
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
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
UR - http://www.scopus.com/inward/record.url?scp=67349243468&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67349243468&partnerID=8YFLogxK
U2 - 10.1007/s00280-008-0844-1
DO - 10.1007/s00280-008-0844-1
M3 - Article
VL - 64
SP - 45
EP - 51
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
SN - 0344-5704
IS - 1
ER -