A phase I and pharmacokinetic study of BAY59: a novel taxane.
OBJECTIVE
To determine the maximum tolerated dose (MTD), the dose limiting toxicities (DLT) and the pharmacokinetics of BAY59, a novel taxane given as a 1-hour intravenous infusion every 3 weeks in patients with advanced refractory solid tumors.


METHODS
Initially, 15 patients with previously treated (median of 4 prior chemotherapy regimens) refractory cancers, but with normal marrow, hepatic and renal function were treated with BAY59 at doses of 15, 30, 50, 75 and 100 mg/m2 using a standard dose escalation design. Subsequently, 11 patients were treated, 5 at 90 mg/m2 and 6 who had had prior oxaliplatin at 75 mg/m2.


RESULTS
At 75 mg/m2, grade 4 neutropenia was noted in 2/6 patients, of whom 1 had grade 4 neutropenia lasting more than 5 days (DLT). At 100 mg/m2, 2/2 patients had febrile neutropenia, with 1 fatality. At 90 mg/m2, 2/5 patients had DLTs, including grade 3 neuropathy, severe lower extremity pain, dehydration and grade 4 neutropenia. The MTD was determined to be 75 mg/m2. A cohort of 6 patients, previously exposed to oxaliplatin, were enrolled at the MTD to evaluate the incidence of neurotoxicity. While DLTs (grade 3 arthralgia, grade 4 neutropenia) were noted in 3/6 patients, there was no increase in the incidence of neurotoxicity. There were no responses. Pharmacokinetics of BAY59 was linear over the doses studied, with a median terminal half-life of 21 h.


CONCLUSIONS
The recommended phase II dose for BAY59 is 75 mg/m2.
Ramnath
N
N
Roswell Park Cancer Institute, Buffalo, NY 14263, USA. nithya.ramnath@roswellpark.org
Hamm
J
J
Schwartz
G
G
Holden
S
S
Eckhardt
S G
SG
Vredenburg
M R
MR
Bernacki
R J
RJ
Lathia
C
C
Kanter
P
P
Creaven
P J
PJ
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D043823:Taxoids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016896:Treatment Outcome
D000972:Antineoplastic Agents, Phytogenic; C493260:BAY59; D043823:Taxoids