In a previous phase I study,
olanzapine was demonstrated to be a safe and effective agent for the prevention of delayed
emesis in
chemotherapy-naïve
cancer patients receiving
cyclophosphamide,
doxorubicin, and/or
cisplatin. Using the maximum tolerated dose of
olanzapine in the phase I trial, a phase II trial was performed for the prevention of
chemotherapy-induced
nausea and
vomiting in
chemotherapy-naïve patients. The regimen was 5 mg/day of oral
olanzapine on the 2 days prior to
chemotherapy, 10 mg on the day of
chemotherapy, day 1, (added to intravenous
granisetron, 10 mcg/kg and
dexamethasone 20 mg), and 10 mg/day on days 2-4 after
chemotherapy (added to
dexamethasone, 8 mg p.o. BID days 2 and 3, and 4 mg p.o. BID day 4). Thirty patients (median age 58.5 years, range 25-84; 23 women; ECOG PS 0, 1) consented to the protocol, and all were evaluable. Complete response (CR) (no
emesis, no rescue) was 100% for the acute period (24 h postchemotherapy), 80% for the delayed period (days 2-5 postchemotherapy), and 80% for the overall period (0-120 h postchemotherapy) in ten patients receiving highly emetogenic
chemotherapy (
cisplatin > or =70 mg/m(2)). CR was also 100% for the acute period, 85% for the delayed period, and 85% for the overall period in 20 patients receiving moderately emetogenic
chemotherapy (
doxorubicin > or =50 mg/m(2)).
Nausea was very well controlled in the patients receiving highly emetogenic
chemotherapy, with no patient having
nausea [0 on scale of 0-10, M.D. Anderson Symptom Inventory (MDASI)] in the acute or delayed periods.
Nausea was also well controlled in patients receiving moderately emetogenic
chemotherapy, with no
nausea in 85% of patients in the acute period and 65% in the delayed and overall periods. There were no grade 3 or 4 toxicities and no significant
pain,
fatigue, disturbed sleep, memory changes,
dyspnea, lack of appetite, drowsiness, dry mouth, mood changes, or
restlessness experienced by the patients. Complete response and control of
nausea in subsequent cycles of
chemotherapy (25 patients, cycle 2; 25 patients, cycle 3; 21 patients, cycle 4) were equal to or greater than cycle 1.
Olanzapine is safe and highly effective in controlling acute and delayed
chemotherapy-induced
nausea and
vomiting in patients receiving highly and moderately emetogenic
chemotherapy.