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 tumor cells.
PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy in treating
patients who have advanced solid tumors.
- Determine the pharmacokinetic profile of gemcitabine, doxorubicin HCl liposome, and
vinorelbine in patients with advanced solid tumors.
- Determine the maximum tolerated dose of this regimen in these patients.
- Determine the toxicity profile of this regimen in these patients.
OUTLINE: This is a dose escalation study.
Patients receive doxorubicin HCl liposome IV over 1-2.5 hours on day 1, gemcitabine IV over
30 minutes on days 1 and 8, and vinorelbine IV over 6-10 minutes on days 1 and 15. Treatment
continues every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of doxorubicin HCl liposome, gemcitabine,
and vinorelbine until the maximum tolerated dose (MTD) is determined. The MTD is defined as
the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting
Patients are followed every 3 months for up to 1 year.
PROJECTED ACCRUAL: Approximately 9-24 patients will be accrued for this study within 12-18
- Histologically confirmed solid tumor not amenable to curative surgery, radiotherapy,
- No brain metastases or primary brain tumors
- 18 and over
- ECOG 0-2
- At least 12 weeks
- WBC at least 3,500/mm3
- Absolute neutrophil count at least 1,500/mm3
- Platelet count at least 100,000/mm3
- Hemoglobin greater than 10 g/dL
- Bilirubin no greater than 1.2 mg/dL
- AST and/or ALT less than 2.5 times upper limit of normal (ULN)
- PT no greater than ULN (anticoagulant independent)
- Creatinine no greater than 1.5 mg/dL AND/OR
- Creatinine clearance greater than 60 mL/min
- No New York Heart Association class III or IV heart disease
- LVEF at least 45% by MUGA or echocardiogram
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- No prior bone marrow or peripheral blood stem cell transplantation following high
- At least 3 weeks since prior biologic therapy for cancer and recovered
- No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)
- See Disease Characteristics
- See Biologic therapy
- No more than 1 prior chemotherapy regimen
- No prior vinca alkaloids
- Prior anthracycline allowed if total dose no greater than 300 mg/m2
- At least 3 weeks since prior chemotherapy (6 weeks for mitomycin or carmustine) and
- At least 3 weeks since prior endocrine therapy for cancer and recovered
- See Disease Characteristics
- No more than 1 prior radiotherapy regimen
- At least 4 weeks since prior large field radiotherapy
- At least 3 weeks since prior radiotherapy for cancer and recovered
- Not specified
Beth A. Overmoyer, MD, FACP
Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center