Dose escalation study of tezacitabine in combination with cisplatin in patients with advanced cancer.
BACKGROUND
The authors performed a dose escalation study of cisplatin and the novel deoxycytidine analog, tezacitabine, to determine the maximum tolerated dose of the combination.


METHODS
Twenty-three patients with advanced cancer and good performance status were accrued to 3 dose levels of tezacitabine (150-270 mg/m(2)) and cisplatin (50 mg/m(2)). Using a 28-day treatment cycle, both drugs were administered on Days 1 and 15.


RESULTS
Hematologic toxicity was the most frequently observed side effect and was dose limiting. Grade 3 or 4 neutropenia and thrombocytopenia complicated 75% and 31% of all cycles, respectively. Nonhematologic toxicities were mild. Among 18 evaluable patients, 2 with upper gastrointestinal tract tumors achieved partial responses and 4 had stable disease.


CONCLUSIONS
Based on dose-limiting neutropenia and thrombocytopenia at the highest dose level, the recommended Phase II doses are 200 mg/m(2) of tezacitabine and 50 mg/m(2) of cisplatin.
Flaherty
Keith T
KT
Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ktflaherty@aol.com
Stevenson
James P
JP
Gallagher
Maryann
M
Giantonio
Bruce
B
Algazy
Kenneth M
KM
Sun
Weijing
W
Haller
Daniel G
DG
O'Dwyer
Peter J
PJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
D003841:Deoxycytidine; D002945:Cisplatin; C086432:tezacitabine