Urokinase combination chemotherapy in small cell lung cancer. A phase II study
Calvo F.A., Hidalgo O.F., González F., Rebollo J., Martín Algarra S., Ortiz de Urbina D., Brugarolas A.
Department of Oncology, Clínica Universitaria de Navarra, Pamplona, Spain.
BACKGROUND AND METHODS
Fifty-one patients with small cell lung cancer (SCLC) were treated with alternating urokinase (UK)-cyclophosphamide-doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH)-vincristine and cisplatin-etoposide-vincristine. UK was given as a loading dose of 3000 micrograms/kg body weight, followed by 3000 micrograms/kg/h for 6 hours. Thoracic irradiation with split technique (46 Gy) and prophylactic cranial irradiation (25 Gy) were administered to responding patients. A second staging was performed in patients exhibiting a clinical complete response (CR) after 1 year.
In 27 patients with limited disease, there were 23 CR and 8 partial responses (PR) (CR, 85.1%; 66.2-95.8% at 95% confidence intervals); in 24 patients with extensive disease, there were 17 CR, 4 PR, and 3 cases with progression. Pathologically proven CR were observed in 59.2% patients with limited disease and 33.3% patients with extensive disease. Survival rates were as follows: in patients with limited disease, 1 year, 85.1%; 2 years, 55.5%; and 3 years, 25.9%; in patients with extensive disease, 1 year, 54.1; and 2 years, 16.9%. Median survival times were 26.3 months (patients with limited disease) and 13.3 months (patients with extensive disease). UK-related toxic effects included four episodes of mild to moderate bleeding, one allergic reaction, and one cerebrovascular accident. Myelotoxicity was severe, with a median of two episodes of Grade III-IV (World Health Organization classification) aplasia per patient.
These results are consistent with a potential benefit of fibrinolytic therapy in combination with chemotherapy in patients with SCLC with limited disease. Additional trials are indicated.
CITATIOIN Cancer. 1992 Dec 1;70(11):2624-30