A Phase I Trial of ZD1694 (TOMUDEX), an Inhibitor of Thymidylate Synthase, in Pediatric Patients With Advanced Neoplastic Disease

Inclusion Criteria

• •DISEASE CHARACTERISTICS:
• •Histologically proven malignancy considered refractory to standard therapy. Objective evidence of progression on prior therapy required.
• •No leukemia.
• •Bone marrow involvement by tumor acceptable. Marrow biopsy required if there is a history of involvement or peripheral counts are inadequate.
• •PRIOR/CONCURRENT THERAPY:
• •Biologic Therapy: Recovery from toxic effects of prior immunotherapy required.
• •Chemotherapy: No more than 2 prior chemotherapy regimens and recovered. At least 2 weeks since myelosuppressive therapy (6 weeks since nitrosoureas).
• •Endocrine Therapy: Not specified.
• •Radiotherapy:
• •No prior central axis irradiation (i.e., skull, spine, ribs, pelvis).
• •Recovery from toxic effects of prior radiotherapy required.
• •Surgery: Not specified.
• •Other: No prior bone marrow transplantation.
• •PATIENT CHARACTERISTICS:
• •Age: 21 and under.
• •Performance status: ECOG 0-2.
• •Life expectancy: At least 8 weeks.
• •Hematopoietic:
• •(unless histologic evidence of bone marrow involvement by tumor).
• •AGC at least 1,500/mm3.
• •Platelet count at least 100,000/mm3.
• •Hemoglobin at least 8.0 g/dL.
• •Prior transfusion acceptable.
• •Hepatic:
• •Bilirubin no greater than 2 times normal.
• •ALT no greater than 2 times normal.
• •Renal:
• •Creatinine less than 1.5 mg/dL OR
• •Creatinine clearance greater than 60 mL/min/1.73 sqm.
• •Cardiovascular: Not specified.
• •Pulmonary: Not specified.
• •OTHER:
• •No significant accumulation of third space fluid.
• •No significant systemic illness (e.g., infection).
• •No pregnant or nursing women.
• •Pregnancy test required in fertile women.
• •All patients or their guardians must sign an informed consent.