RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die. Combining more than one drug may kill more cancer cells.
PURPOSE: Phase I trial to study the effectiveness of combining ZD0473 and doxorubicin in
treating patients who have advanced solid tumors or lymphoma.
OBJECTIVES: I. Determine the maximum tolerated dose of ZD0473 and doxorubicin HCl liposome
in patients with advanced or metastatic solid tumors or lymphoma. II. Determine the
qualitative and quantitative toxic effects of this regimen in this patient population. III.
Determine the pharmacokinetics of these drugs in this patient population. IV. Determine the
antitumor activity of this regimen in this patient population.
OUTLINE: This is a dose-escalation study. Patients receive doxorubicin HCl liposome IV over
60 minutes followed by ZD0473 IV over 60 minutes on day 1. Treatment repeats every 28 days
for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity.
Patients with partial response (PR) or complete response (CR) may continue treatment until
disease progression or until 2 courses after maximum response. Cohorts of 3-6 patients
receive escalating doses of doxorubicin HCl liposome and ZD0473 until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose at which 2 of 3 or 3 of 6 patients
experience dose-limiting toxicity. Patients are followed at 4 weeks and 3 months. Patients
with PR or CR ongoing continue follow-up every 3 months until relapse.
PROJECTED ACCRUAL: Approximately 24 patients will be accrued for this study.
DISEASE CHARACTERISTICS: Histologically confirmed advanced or metastatic solid tumors or
lymphoma Refractory to standard curative therapy OR No curative therapy exists
Serologically, clinically, and/or radiographically assessable disease No newly diagnosed
brain metastases Intracranial disease that is stable for at least 6 months allowed
PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy:
Not specified Hematopoietic: Absolute granulocyte count at least 1,500/mm3 Platelet count
at least 100,000/mm3 Hepatic: Bilirubin no greater than upper limit of normal (ULN) AST or
ALT no greater than 2.0 times ULN Alkaline phosphatase no greater than 2.0 times ULN
Renal: Creatinine no greater than ULN Creatinine clearance at least 60 mL/min
Cardiovascular: Ejection fraction at least 50% Other: No underlying medical condition that
would preclude study or that is uncontrolled No active serious infection No neurotoxicity
or preexisting grade 3 or higher neuropathy Not pregnant or nursing Negative pregnancy
test Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY: Biologic therapy: At least 5 days since prior immunotherapy
Chemotherapy: At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas and
similar compounds) No more than 3 prior chemotherapy regimens for metastatic disease No
prior anthracycline exposure exceeding 300 mg/m2 doxorubicin No prior doxorubicin HCl
liposome Endocrine therapy: At least 5 days since prior hormonal therapy Radiotherapy: At
least 3 weeks since prior radiotherapy and recovered No prior radiotherapy to more than
30% of functioning bone marrow Surgery: At least 3 weeks since prior major surgery Other:
No other concurrent experimental drugs No other concurrent anticancer therapy