ABSTRACT
Because tamoxifen and all-trans-retinoic acid (ATRA) have additive antitumor effects in preclinical systems, we performed a Phase I/II clinical trial of this combination in patients with advanced breast cancer. Patients with potentially hormone-responsive advanced breast cancer were enrolled. All received 20 mg of tamoxifen by mouth daily. Consecutive cohorts of 3-6 patients were treated on odd-numbered weeks with ATRA at doses of 70, 110, 150, 190, or 230 mg/m2/day. Twenty-six patients were entered in this trial; 25 were evaluable. A dose of 230 mg/m2 ATRA produced unacceptable headache and dermatological toxicity, but doses < or = 190 mg/m2 were tolerable. Two of 7 patients with measurable disease responded. Seven of 18 patients with evaluable, nonmeasurable disease achieved disease stability for more than 6 months. Plasma AUCs on day 1 of successive weeks of treatment were stable over time. A nonsignificant decrease in serum insulin-like growth factor I levels was noted during treatment, but this trend was similar to that observed in three "control" patients treated with tamoxifen alone. When given with daily tamoxifen, the maximum tolerated dose of ATRA that could be given on alternate weeks was 190 mg/m2/day. This schedule of ATRA resulted in repeated periods of exposure to potentially therapeutic concentrations of ATRA. Declines in the serum insulin-like growth factor I concentrations observed in patients treated with tamoxifen and ATRA were similar to those observed in patients treated with tamoxifen alone. Objective responses were observed, some in patients who had previously progressed while receiving tamoxifen, suggesting that further studies would be of interest.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Tamoxifen/therapeutic use , Tretinoin/therapeutic use , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Biomarkers/blood , Breast Neoplasms/pathology , Drug Administration Schedule , Female , Humans , Insulin-Like Growth Factor Binding Protein 1/blood , Insulin-Like Growth Factor Binding Protein 3/blood , Insulin-Like Growth Factor I/analysis , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Tamoxifen/administration & dosage , Tamoxifen/adverse effects , Tretinoin/administration & dosage , Tretinoin/adverse effectsABSTRACT
OBJECTIVE: To provide an overview of the most common toxic effects associated with biotherapy and strategies for effective patient management, predominantly in the outpatient setting. DATA SOURCES: Review articles and book chapters related to nursing care of patients receiving biotherapy. CONCLUSIONS: Biological response modifiers can produce several toxic effects that may have a significant impact on the patient's quality of life. Additionally, biotherapy is being delivered more frequently in the ambulatory and home care settings. IMPLICATIONS FOR NURSING PRACTICE: As the role of biotherapy expands in the treatment of cancer, oncology nurses must be attuned to the special needs of patients receiving this therapy. Nurses must be knowledgeable of not only symptom management but reimbursement and managed care issues as well.
