A Phase I Trial of Lometrexol Sodium and Paclitaxel Adminsitered Intravenously Every 21 Days in Conjunction With Oral Folic Acid in Patients With Solid Tumors

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically proven locally advanced or metastatic solid tumor
that is refractory to standard therapies or for which there are no therapies of
potential major benefit

- Measurable disease

- No hematologic malignancies, including leukemia, lymphoma, or multiple myeloma

- No symptomatic effusions or ascites unless drained before study entry

- No clinically apparent CNS metastases or carcinomatous meningitis

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- WHO 0-1

Life expectancy:

- At least 12 weeks

Hematopoietic:

- Absolute neutrophil count at least 1,500/mm^3*

- Platelet count at least 100,000/mm^3*

- Hemoglobin at least 9.0 g/dL* NOTE: * Without growth factor support

Hepatic:

- Bilirubin no greater than 2.0 mg/dL

- SGOT and SGPT no greater than 2.5 times upper limit of normal (ULN) (5 times ULN if
tumor involvement of liver)

- Albumin greater than 2.5 g/dL

Renal:

- Glomerular filtration rate at least 65 mL/min

Gastrointestinal:

- No inflammatory bowel disease

- No radiation enteritis

- No malabsorption syndrome

Other:

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No known hypersensitivity to study drugs or related compounds (e.g., LY309887,
multi-targeted antifolate, AG-2034, methotrexate, docetaxel, or polyoxyethylated
castor oil)

- No active uncontrolled infection unless approved by the investigator

- No other severe concurrent disease that would preclude study therapy

- No body surface area greater than 3.0 m^2

- No known vitamin B12 deficiency

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- No concurrent routine or prophylactic filgrastim (G-CSF), sargramostim (GM-CSF), or
epoetin alfa

- No concurrent biologic-response modifiers

Chemotherapy:

- At least 4 weeks since prior chemotherapy (6 weeks for mitomycin, carboplatin, or
nitrosourea) and recovered

- No other concurrent cytotoxic chemotherapy

Endocrine therapy:

- No concurrent hormonal therapy

Radiotherapy:

- Recovered from prior radiotherapy

- No prior radiotherapy to 25% or more of bone marrow (e.g., whole-pelvic irradiation)

- No concurrent radiotherapy (including palliative radiotherapy)

Surgery:

- At least 4 weeks since prior major surgery and recovered

Other:

- At least 4 weeks since prior investigational agent

- No more than 2 prior therapies for locally advanced or metastatic solid tumor

- No other concurrent investigational agent

- No concurrent trimethoprim, co-trimoxazole, proguanil, or pyrimethamine