A phase I study of oral uracil/ftorafur (UFT) plus leucovorin and bis-acetato-ammine-dichloro-cyclohexylamine-platinum IV (JM-216) each given over 14 days every 28 days.
OBJECTIVE
To determine the feasibility, maximal tolerated doses, and response rates for a combined regimen of the platinum and 5-fluorouracil oral analogues bis-acetato-ammine-dichloro-cyclohexyl-amine platinum(IV) (JM-216) and uracil/ftorafur (UFT) coadministered as a 14 consecutive-day every 28-day schedule.


METHODS
Of 20 patients enrolled in this investigation, 17 on the following dose escalation scheme were evaluable for toxicity and/or response: I UFT 300 mg/day, JM-216 5 mg/day (three patients), II UFT 300 mg/day, JM-216 10 mg/day (four patients), III UFT 300 mg/day, JM-216 20 mg/day (ten patients).


RESULTS
All 17 evaluable patients were evaluable for toxicity. At dose level III dose-limiting nausea and emesis were observed in one patient despite maximal antiemetic support. Importantly, neurotoxicity and nephrotoxicity were not observed at the JM-216 dose levels examined in this study. This observation is consistent with results seen with single agent JM-216.


CONCLUSIONS
For JM-216 and UFT administered at 20 mg/day and 300 mg/day over 14 days, nausea and emesis were observed as the principal dose-limiting toxicities. These doses are considerably below the maximally tolerated doses of single agent JM-216 and UFT. Shorter administration schedules should be explored in an attempt to increase the dose intensity and minimize the toxicity of this combination oral regimen.
DeMario
M D
MD
Department of Medicine, The University of Chicago, Medical Center, IL 60637-1470, USA.
Ratain
M J
MJ
Vogelzang
N J
NJ
Mani
S
S
Vokes
E E
EE
Fleming
G F
GF
Melton
K
K
Johnson
S
S
Benner
S
S
Lebwohl
D
D
D000284:Administration, Oral; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D009369:Neoplasms / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects; D014839:Vomiting / Q000139:chemically induced
D004338:Drug Combinations; D009944:Organoplatinum Compounds; C096910:UFT(R) drug; D005641:Tegafur; D014498:Uracil; C081294:satraplatin; D002955:Leucovorin