Pemetrexed Disodium and Docetaxel in Treating Patients With Advanced Solid Tumors

Phase I Dose Escalation Trial of Biweekly Alimta (With Vitamin Supplementation) in Combination With Taxotere in Advanced Solid Tumor Patients

RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells of by stopping them from dividing. Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of giving pemetrexed disodium and docetaxel together 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