Phase I study of 3'-deamino-3'-(2-methoxy-4-morpholinyl)doxorubicin (FCE 23762, PNU 152243) administered on a daily x3 schedule.
BACKGROUND
3'-Deamino-3'-(2-methoxy-4-morpholinyl)doxorubicin (FCE 23762, PNU 152243) is a highly lipophilic doxorubicin derivative which possesses potent in vitro and in vivo antitumor activity. Previous phase I studies had been conducted using a single bolus every 28 days.


METHODS
We conducted a phase I study of FCE 23762 on a daily x3 every 28 days schedule. Thirty patients received 68 cycles of therapy at 5 dose levels (200-600 micrograms/m2/d).


RESULTS
Prolonged neutropenia and thrombocytopenia were the dose-limiting toxicities. Other nonhematological toxicities included nausea and vomiting, anorexia, fatigue and transient elevations of serum creatinine and hepatic transaminases. No cardiac toxicity was demonstrated. There were no partial or complete antitumor responses.


CONCLUSIONS
The recommended phase II dose using the schedule defined in this study is 500 micrograms/m2/dx3.
Ratain
M J
MJ
Department of Medicine, University of Chicago, IL, USA.
Skoog
L A
LA
O'Brien
S M
SM
Cooper
N
N
Schilsky
R L
RL
Vogelzang
N J
NJ
Gerber
M
M
Narang
P K
PK
Nicol
S J
SJ
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*
D000903:Antibiotics, Antineoplastic; C066998:methoxy-morpholinyl-doxorubicin; D004317:Doxorubicin