Efficacy of sequential high-dose doxorubicin and ifosfamide compared with standard-dose doxorubicin in patients with advanced soft tissue sarcoma: an open-label randomized phase II study of the Spanish group for research on sarcomas.
OBJECTIVE
To assess the progression-free survival (PFS) and antitumor response to standard-dose doxorubicin compared with sequential dose-dense doxorubicin and ifosfamide in first-line treatment of advanced soft tissue sarcoma.


METHODS
Patients with measurable advanced soft tissue sarcoma, Eastern Cooperative Oncology Group (ECOG) performance status (PS) < 2, between the ages 18 and 65 years, and with adequate bone marrow, liver, and renal function were entered in the study. The stratifications were: ECOG PS (0 v 1), location of metastases, and potentially resectable disease. Patients were randomly assigned to either doxorubicin 75 mg/m(2) given as a bolus injection every 3 weeks for 6 cycles (arm A) or doxorubicin at 30 mg/m(2) per day for 3 consecutive days once every 2 weeks for 3 cycles followed by ifosfamide at 12.5 g/m(2) delivered by continuous infusion over 5 days once every 3 weeks for 3 cycles with filgastrim or pegfilgastrim support (arm B).


RESULTS
Between December 2003 and September 2007, 132 patients were entered onto the study. Febrile neutropenia, asthenia, and mucositis were more frequent in the arm B. The interim preplanned analysis for futility allowed the premature closure. Objective responses were observed in 23.4% of assessable patients in arm A and 24.1% in arm B. PFS was 26 weeks in the arm A and 24 weeks in arm B (P = .88). Overall survival did not differ between the two therapeutic arms (P = .14).


CONCLUSIONS
Single-agent doxorubicin remains the standard treatment in fit patients with advanced soft tissue sarcoma.
Maurel
Joan
J
Medical Oncology Department, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Hospital Clínic, Barcelona, Spain. jmaurel@clinic.ub.es
López-Pousa
Antonio
A
de Las Peñas
Ramón
R
Fra
Joaquín
J
Martín
Javier
J
Cruz
Josefina
J
Casado
Antonio
A
Poveda
Andrés
A
Martínez-Trufero
Javier
J
Balañá
Carmen
C
Gómez
María Auxiliadora
MA
Cubedo
Ricardo
R
Gallego
Oscar
O
Rubio-Viqueira
Belen
B
Rubió
Jordi
J
Andrés
Raquel
R
Sevilla
Isabel
I
de la Cruz
Juan Jose
JJ
Del Muro
Xavier García
XG
Buesa
Jose María
JM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D012509:Sarcoma / Q000188:drug therapy*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy*; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
D000970:Antineoplastic Agents; D004317:Doxorubicin; D007069:Ifosfamide