Inclusion Criteria

DISEASE CHARACTERISTICS:

- Pathologically confirmed newly diagnosed acute myeloid leukemia (AML)

- Subtypes M0, M1, M2, M4-7 disease

- No newly diagnosed acute promyelocytic leukemia (M3)

- Any of the following diseases:

- De novo disease

- Secondary AML

- Myelodysplasia (MDS)-related AML (MDS/AML)

- Treatment-related AML

- Previously untreated disease

- Patients who have received prior hydroxyurea alone or non-cytotoxic therapies
for MDS (e.g., thalidomide, interferon, cytokines, 5-azacytidine, or revlimid)
will be eligible for this study

- Must be considered ineligible for traditional antileukemia chemotherapy

- No hyperleukocytosis with ≥ 30,000 blasts/uL or rapidly rising blast count with
projected doubling time of ≤ 2 days

- Patients may receive hydroxyurea to lower blast count to < 30,000 blasts/uL up
to 24 hours before beginning tipifarnib and etoposide

- No active CNS leukemia

PATIENT CHARACTERISTICS:

Inclusion criteria:

- ECOG performance status 0-2

- Serum creatinine ≤ 2.0 mg/dL

- SGOT and SGPT ≤ 3 times upper limit of normal

- Bilirubin ≤ 2 mg/dL

Exclusion criteria:

- Active, uncontrolled infection

- Patients with infection under active treatment and controlled with
antimicrobials are eligible

- Presence of other life-threatening illnesses

- Patients with mental deficits and/or psychiatric history that preclude them from
giving informed consent or from following protocol

- Allergies to imidazoles (e.g., clotrimazole, ketoconazole, miconazole, or econazole)

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior tipifarnib or etoposide

- No concurrent radiotherapy, immunotherapy, or other chemotherapy

- No concurrent enzyme-inducing anticonvulsants (e.g., phenytoin, fosphenytoin,
phenobarbital, primidone, carbamazepine, or oxcarbazepine)

- Patients may be changed to non-enzyme-inducing anticonvulsants and stabilized
before starting study treatment