Palonosetron and Dexamethasone With or Without Dronabinol in Preventing Nausea and Vomiting in Patients Receiving Chemotherapy For Cancer

OBJECTIVES:

- To determine whether dronabinol can add significantly to the antiemetic protection
provided by a standard palonosetron hydrochloride and dexamethasone regimen for
patients receiving moderately emetogenic chemotherapy.

- To determine the tolerability of dronabinol when added to a regimen of dexamethasone
and palonosetron hydrochloride administered for the prevention of acute and delayed
nausea and vomiting caused by moderately emetogenic chemotherapy.

- To determine tolerability, in terms of treatment-limiting toxicities, observed with the
three-drug combination.

OUTLINE: This is a multicenter study. Patients are stratified according to study center.
Patients receive scheduled chemotherapy (cyclophosphamide and/or doxorubicin hydrochloride)
beginning on day 1. Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive palonosetron hydrochloride IV and dexamethasone IV 30 minutes
before chemotherapy administration on day 1. Patients also receive oral dronabinol 3
times a day for 5 days beginning 30 minutes before chemotherapy administration on day
1.

- Arm II: Patients receive palonosetron hydrochloride and dexamethasone as in arm I.
Patients also receive an oral placebo 3 times a day for 5 days beginning 30 minutes
before chemotherapy on day 1.

In both arms, treatment continues in the absence of nausea or vomiting within 24 hours after
initiation of chemotherapy.

Patients complete a Daily Assessment of Nausea and Vomiting questionnaire after the
administration of chemotherapy on days 1-5.

Patients are followed at the completion of course 1 of chemotherapy (days 14-28).

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed solid tumors

- Receiving a moderately emetogenic chemotherapy regimen for the first time

- Patients may be chemotherapy naive or may have previously received a mildly
emetogenic agent, such as a taxane, if no nausea/vomiting was experienced with
that chemotherapy

- Scheduled to receive cyclophosphamide ≤ 1,500 mg/m^2 IV and/or doxorubicin
hydrochloride ≥ 40 mg/m^2 IV given as single doses on day 1 of chemotherapy
regimen

- Patients on combination regimens with these agents are eligible

- No concurrent moderately emetogenic chemotherapy (Hesketh Level 3-4) after day 1
of the study period

- Hesketh Level 1-2 chemotherapy on days 2-5 allowed

- No other physical causes for nausea or vomiting not related to chemotherapy
administration (i.e., bowel obstruction)

- No recent history of unexplained nausea or vomiting or history of frequent nausea or
vomiting

- No uncontrolled primary or metastatic CNS tumor (including those with uncontrolled
seizures)

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- WBC ≥ 3,000/mm^3

- Absolute granulocyte count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Creatinine ≤ 1.5 x upper limit of normal (ULN)

- Bilirubin ≤ 2.5 x ULN

- Transaminases ≤ 2.5 x ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No active bacterial or fungal infection for which administration of a corticosteroid
would be contraindicated

- No hypersensitivity to any of the study agents

- No sensitivity to sesame oil

- No previous poor tolerance of cannabinoids

- No habitual cannabinoid use or unwillingness to avoid the use of marijuana during the
study period

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- At least 30 days since prior treatment with any investigational agent

- No prior chemotherapy

- No prior dronabinol or nabilone

- No concurrent highly emetogenic chemotherapy (i.e.,cisplatin, streptozotocin,
dacarbazine, carmustine, hexamethylmelamine, mechlorethamine, procarbazine) [Hesketh
Level 5])

- No concurrent cranial, abdominal, or pelvic radiotherapy

- No concurrent corticosteroid treatment other than the study drug dose

- No other concurrent potential or known prophylactic antiemetic agents

- Chronically used benzodiazepines may be continued as a single nightly dose for
sleep

- No other concurrent investigational agents