Phase III Comparison of Doxorubicin and Dacarbazine Given by Bolus Versus Infusion in Patients With Soft-Tissue Sarcomas: A Southwest Oncology Group Study

Abstract

Disseminated soft-tissue sarcomas are a group of uncommon malignancies generally treated in a uniform manner. This study questioned the impact of schedule on response rate and toxicity in patients with metastatic soft-tissue sarcoma treated with the two-drug combination doxorubicin and dacarbazine. Patients were randomly assigned to receive either bolus therapy with doxorubicin at a dose of 60 mg/m2 and dacarbazine at a dose of 750 mg/m2 intravenously on day 1 (118 patients) or infusional therapy with doxorubicin at 60 mg/m2 and dacarbazine at 750 mg/m2 delivered by continuous intravenous infusion for 96 hours on days 1-4 (122 patients). Chemotherapy was to be repeated every 3 weeks. A unique feature of this cooperative group protocol was a provision for surgical resection of residual disease in patients with a partial response or with stable disease following chemotherapy. Similar overall response rates (17% in both treatment arms) and complete response rates (5% in both treatment arms) were observed. For patients receiving bolus therapy, the median response duration was 19.6 months for those in complete remission and 6.6 months for those in partial remission. For patients receiving infusional therapy, the median response duration was 12.6 months for those in complete remission and 9.3 months for those in partial remission. Examination of dose intensity received when combining treatment arms revealed a weak doxorubicin dose-response relationship. There was no difference in median survival times between the two treatment arms (bolus therapy, 10.6 months; infusional therapy, 10.5 months; logrank P = .97). Analysis of toxic effects favored infusional therapy. Significant reductions in cardiac toxicity (all events, P = .04; clinical events, P = .01) and nausea and emesis (P = .04) were seen in infusional therapy. Of 47 patients eligible for cytoreductive surgery following chemotherapy, 12 received surgery, and of those 12, eight were rendered disease free. The use of a 96-hour continuous intravenous infusion of doxorubicin-dacarbazine was comparable therapeutically with bolus dosing of these two agents and was better tolerated by the patients.

Ki67 and p53 in gastrointestinal stromal tumors - GIST

“…Imatinib is a potent inhibitor of KIT signaling tyrosine kinase inhibitor (5,6,10,20,29) . Before the use of imatinib, the median survival of the patients with resectable disease was 66 months (5,9) and 9 to 12 months in irresectable disease (3,4,9,11,12,14,38) .…”

Gastrointestinal Stromal Tumor of the Rectovaginal Septum, a Diagnosis Challenge

“…The use of antibodies to kit, as part of an immunohistochemical panel and in combination with traditional histological and clinical examinations, means that it is possible to distinguish clearly GISTs from other gastrointestinal tract tumours. In addition, the tyrosine kinase inhibitor imatinib mesilate (Gleevec™) represents a major breakthrough in the treatment of GISTs, as it has significant antitumour activity in these neoplasms, which are generally resistant to cytotoxic chemotherapy (Zalupski et al 1991;Ronellenfitsch et al, 2008). A second targeted tyrosine kinase inhibitor, sunitinib malate (Sutent™), has been approved for the treatment of imatinibresistant gastrointestinal stromal tumors.…”

Tumores del estroma gastrointestinal (GIST), un particular tipo de neoplasia

“…La quimioterapia sistémica no ha sido efectiva. Hay algunos estudios con baja tasa de respuesta a combinaciones de doxorrubicina y dacarbacina 39 , dacarbacina más mitomicina c, doxorrubicina y cisplatino 40 y no hay respuesta a etopósido e ifosfamida 41 . La falta de respuesta a las drogas usualmente usadas en sarcomas de partes blandas se debería a la frecuente expresión de la glicoproteína P y proteína a multiresistencia a drogas 1(MDR1) en estos tumores, relacionados con la resistencia a drogas 42 .…”