Dose-escalation study of fixed-dose rate gemcitabine combined with capecitabine in advanced solid malignancies.
OBJECTIVE
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 <or=2) received capecitabine 500 mg/m(2) PO BID days 1-14 and FDR gemcitabine (400-1,000 mg/m(2) escalated by 200 mg/m(2) increments) at 10 mg/m(2)/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 >or=3 toxicity was myelosuppression, particularly neutropenia. At dose level 4 (1,000 mg/m(2) gemcitabine), two out of five evaluable patients had a DLT (grade 4 neutropenia >or=7 days). At dose level 3 (800 mg/m(2) gemcitabine), one patient had a DLT (grade 3 neutropenia >or=7 days) among six evaluable patients. Therefore, the MTD and recommended phase II dose was designated as capecitabine 500 mg/m(2) PO BID days 1-14 with 800 mg/m(2) FDR gemcitabine days 1 and 8 infused at 10 mg/m(2) 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.
Attia
Steven
S
University of Wisconsin Paul P Carbone Comprehensive Cancer Center Madison, Madison, WI 53792, USA. attia@wisc.edu
Morgan-Meadows
Sherry
S
Holen
Kyle D
KD
Bailey
Howard H
HH
Eickhoff
Jens C
JC
Schelman
William R
WR
Traynor
Anne M
AM
Mulkerin
Daniel L
DL
Campbell
Toby C
TC
McFarland
Thomas A
TA
Huie
Michael S
MS
Cleary
James F
JF
Tevaarwerk
Amye J
AJ
Alberti
Dona B
DB
Wilding
George
G
Liu
Glenn
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D015331:Cohort Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced*; D016896:Treatment Outcome; D000093542:Gemcitabine
D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil; D000093542:Gemcitabine