Pemetrexed Disodium and Docetaxel in Treating Patients With Advanced Solid Tumors

OBJECTIVES:

Primary

- To determine the maximum-tolerated dose of the combination of pemetrexed disodium and
docetaxel when administered on a day 1 and day 15 dosing schedule.

Secondary

- To specifically characterize the toxicity profile for the combination of biweekly
pemetrexed disodium and docetaxel.

- To investigate the antitumor activity in patients with advanced solid tumors as
measured by RECIST criteria for patients with measurable disease or tumor markers for
patients with non-measurable disease.

- To determine the recommended phase II dose of the combination of pemetrexed disodium
and docetaxel on a biweekly dosing schedule.

OUTLINE: This is a dose-escalation study.

Patients receive pemetrexed disodium IV over 10 minutes and docetaxel IV on days 1 and 15.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

DISEASE CHARACTERISTICS:

- Diagnosis of advanced or recurrent solid tumors

- Patients for whom docetaxel is considered appropriate anticancer therapy;
docetaxel is currently approved for use in patients with the following solid
tumors:

- Non-small cell lung (NSCLC)

- Breast

- Prostate

- Esophageal

- Head and neck

- Ovarian

- Gastric

- Measurable or non-measurable disease

- No squamous cell NSCLC

- Controlled brain metastases allowed

- Clinically stable with no signs of progression by MRI or CAT scan ≥ 60 days
after treatment

- Patients must be asymptomatic with no steroid requirements

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- Life expectancy ≥ 12 weeks

- WBC ≥ 3,000/mm^3*

- ANC ≥ 1,500/mm^3*

- Hemoglobin ≥ 9 g/dL

- Platelet count ≥ 100,000/mm^3

- Total bilirubin normal

- AST, ALT, and alkaline phosphatase (AP) must meet one of the following criteria:

- AST or ALT ≤ 3** times upper limit of normal (ULN) AND AP normal

- AST or ALT ≤ 1.5 times ULN AND AP ≤ 2.5 times ULN

- AST or ALT normal AND AP ≤ 5 times ULN

- Calculated creatinine clearance ≥ 45 mL/min OR GFR measured by Tc99m-DPTA serum
clearance method

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for ≥ 3 months after
completion of study treatment

- Able to interrupt aspirin or other NSAIDs pre- and post- twice-monthly drug dosing

- Able to take folic acid, vitamin B12, or corticosteroids

- No uncontrolled serious active infections

- No pre-existing peripheral neuropathy > grade 1

- No significant cardiac disease (i.e., uncontrolled high blood pressure, unstable
angina, congestive heart failure within the past 6 months, LVEF < normal, myocardial
infarction within the past year, or serious cardiac arrhythmias requiring medication)

- No known severe hypersensitivity reaction to docetaxel or other drugs formulated in
polysorbate 80 NOTE: *No concurrent colony-stimulating factors to maintain these
values

NOTE: **For patients with liver metastases, AST or ALT ≤ 5 times ULN AND AP normal

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Have received 0-1 prior systemic therapy regimens (prior adjuvant chemotherapy will
be considered a prior systemic therapy regimen)

- At least 4 weeks since prior systemic anticancer therapy (6 weeks for mitomycin C and
nitrosoureas)

- At least 2 weeks since prior radiotherapy and recovered from the side effects to ≤
grade 1

- At least 2 weeks since prior pleurodesis

- No concurrent radiotherapy