Patient case: 84-year-old male with glioblastoma; genetic feature: CDK6

Clinical trial: Fluorouracil Plus UCN-01 in Treating Patients With Advanced or Refractory Solid Tumors

Summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. UCN-01 may increase the effectiveness of a chemotherapy drug by making tumor cells more sensitive to the drug.
  PURPOSE: Phase I trial to study the effectiveness of fluorouracil plus UCN-01 in treating patients who have advanced or refractory solid tumors.

Detailed description: OBJECTIVES:
  -  Determine the maximum tolerated dose, dose limiting toxicity, and toxicity profile of fluorouracil with UCN-01 in patients with advanced or refractory solid tumors.
  -  Assess the clinical pharmacokinetics of this regimen and correlate with observed toxicities in these patients.
  -  Obtain preliminary data on the therapeutic activity of this regimen in these patients.
  OUTLINE: This is a dose escalation study of fluorouracil.
  Patients receive fluorouracil IV over 24 hours on days 1, 8, 15, and 22. Patients receive an initial dose of UCN-01 IV over 72 hours beginning on day 2 during course 1 and then maintenance UCN-01 IV over 36 hours beginning on day 2 during subsequent courses. Treatment repeats every 4 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity.
  Cohorts of 3-6 patients receive escalating doses of fluorouracil until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicity.
  PROJECTED ACCRUAL: Approximately 6-48 patients will be accrued for this study within approximately 14 months.

Eligibility: DISEASE CHARACTERISTICS:
  -  Histologically confirmed solid tumor that is refractory to standard therapy or for which no standard therapy exists
  -  Measurable or evaluable disease
  -  No CNS metastasis or primary CNS malignancy
  PATIENT CHARACTERISTICS:
  Age:
  -  18 and over
  Performance status:
  -  Karnofsky 60-100%
  Life expectancy:
  -  Not specified
  Hematopoietic:
  -  WBC greater than 3,500/mm^3
  -  Absolute neutrophil count at least 1,500/mm^3
  -  Platelet count at least 100,000/mm^3
  Hepatic:
  -  Bilirubin no greater than 1.5 mg/dL
  -  SGOT and SGPT no greater than 2.5 times upper limit of normal
  Renal:
  -  Creatinine no greater than 1.5 mg/dL OR
  -  Creatinine clearance greater than 60 mL/min
  Cardiovascular:
  -  No history of coronary artery disease documented by prior myocardial infarction, angiography, or coronary-artery bypass grafting
  -  No cardiac arrhythmias or congestive heart failure within the past 6 months
  -  Stable atrial fibrillation on standard treatment allowed at discretion of investigator
  Pulmonary:
  -  DLCO at least 60% of predicted
  Other:
  -  Not pregnant or nursing
  -  Negative pregnancy test
  -  Fertile patients must use effective contraception during and for 2 months after study
  -  No active serious or uncontrolled infection
  -  HIV negative
  -  No diabetes
  -  No other medical condition that would preclude study
  PRIOR CONCURRENT THERAPY:
  -  See Disease Characteristics
  Biologic therapy:
  -  At least 4 weeks since prior immunotherapy and recovered
  Chemotherapy:
  -  At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin) and recovered
  -  Prior fluorouracil allowed
  Endocrine therapy:
  -  Not specified
  Radiotherapy:
  -  No prior mediastinal radiotherapy
  -  At least 4 weeks since prior radiotherapy and recovered
  Surgery:
  -  Not specified
  Other:
  -  No concurrent anticonvulsant medications

Relevance to patient case: not relevant