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