Phase I Study Of Octreotide Acetate (Sandostatin) (SMS) As A Biomodulator Of Doxorubicin (DOX)
Phase I Study Of Octreotide Acetate (Sandostatin) (SMS) As A Biomodulator Of Doxorubicin (DOX)
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Octreotide may help doxorubicin kill more cancer cells by making tumor cells more sensitive to the drug.
PURPOSE: Phase I trial to study the effectiveness of octreotide and doxorubicin in treating patients who have advanced cancer.
OBJECTIVES: I. Determine the toxicity and maximum tolerated dose of octreotide administered with doxorubicin in patients with advanced cancer. II. Determine the pharmacokinetics and pharmacodynamics of this treatment regimen in these patients.
OUTLINE: This is a dose escalation study of octreotide. Patients receive doxorubicin IV over 5 minutes on day 1 of course 1. For all subsequent courses, patients receive octreotide SC continuously on days 1-7 and doxorubicin IV over 5 minutes on day 5. Treatment continues every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients with stable or responsive disease after 3 courses of therapy receive a maximum of 6 additional courses. Cohorts of 3-6 patients receive escalating doses of octreotide 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 21-30 patients will be accrued for this study.
DISEASE CHARACTERISTICS: Histologically confirmed malignancy ineligible for therapy of proven greater benefit than doxorubicin alone Measurable or evaluable disease
PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: WBC at least 3,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 2 mg/dL SGOT no greater than 4 times normal Renal: Creatinine no greater than 2 mg/dL Cardiovascular: LVEF at least 50% No compensated or uncompensated congestive heart failure Other: Not pregnant Fertile patients must use effective contraception during and for 2 months after study No history of gallstones with gallbladder in place
PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics At least 3 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosourea) and recovered No more than 240 mg/m2 total cumulative dose of prior doxorubicin Endocrine therapy: Prior octreotide allowed Recovered from prior octreotide Radiotherapy: At least 3 weeks since prior radiotherapy and recovered Surgery: Not specified