The feasibility of high-dose chemotherapy in breast cancer patients with impaired left ventricular function.
Breast cancer patients with cardiac disease are usually excluded from clinical trials of high-dose chemotherapy. We treated 52 patients with inflammatory and/or metastatic disease with sequential high-dose melphalan and stem cell rescue followed by high-dose thiotepa and stem cell rescue. Stem cells were mobilized with cyclophosphamide and/or paclitaxel and filgrastim. Left ventricular ejection fraction (LVEF) was measured by equilibrium radionuclide angiocardiography (ERNA) at baseline, after each course of chemotherapy and 4 weeks after completing both transplants. The mean absolute decrease in LVEF after the two transplants was 3.6% (P = 0. 008 for the comparison with baseline LVEF), and most of this drop (-2.5%, P = 0.007) occurred after mobilization. Unexpectedly, paclitaxel was associated with a mean absolute decrease in LVEF of 3. 4% (P = 0.032, n = 19), cyclophosphamide alone was not associated with a significant change in LVEF (-1.3%, P = 0.23), but mobilization with sequential paclitaxel and cyclophosphamide resulted in a mean absolute drop of 4.9% in LVEF (P = 0.009). Twelve patients were found to have a reduced LVEF (<50%) at least once during treatment and had a mean absolute decrease in LVEF of 10% (P = 0.008) from baseline, compared with a drop of only 1.8% (P = 0. 176) in the patients without impaired LV function. Although two of these 12 patients developed symptomatic heart failure, their cardiac symptoms were easily treated and there were no cardiac deaths. We conclude that our protocol has acceptable cardiac toxicity and breast cancer patients with impaired LV function should not be denied high-dose chemotherapy if otherwise indicated.
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8032, USA.
M
M
Rose
F A
FA
Lee
A
A
Gollerkeri
E
E
D'Andrea
A
A
Psyrri
T
T
Bdolah-Abram
B A
BA
Burtness
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use / Q000633:toxicity*; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000628:therapy; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005500:Follow-Up Studies; D019650:Hematopoietic Stem Cell Mobilization / Q000009:adverse effects; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology; D013318:Stroke Volume / Q000187:drug effects; D015996:Survival Rate; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced*
D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel