TY - JOUR
T1 - Efficacy of ifosfamide and doxorubicin given as a phase II "window" in children with newly diagnosed metastatic rhabdomyosarcoma
T2 - A report from the intergroup rhabdomyosarcoma study group
AU - Sandler, E.
AU - Lyden, E.
AU - Ruymann, F.
AU - Maurer, H.
AU - Wharam, M.
AU - Parham, D.
AU - Link, M.
AU - Crist, W.
PY - 2001
Y1 - 2001
N2 - Background. The cure rate for children/ adolescents with localized rhabdomyosarcoma (RMS) has tripled over the past 25 years, but patients with metastatic disease at presentation have not benefited similarly, and urgently need new therapy. We evaluated a new drug pair, ifosfamide+doxorubicin, for such patients. Procedure. We estimated the complete and partial response rates (i.e., CR and PR) of 152 previously untreated children/adolescents with metastatic RMS entered on the IRS-IV pilot from July 1988 to October 1991 who received an "up-front window" of ifosfamide (1.8 gm/m2/ day for 5 days) and doxorubicin (30 mg/m2/day for 2 days) given every 3 weeks for 12 weeks. This was followed by combination chemotherapy with vincristine, actinomycin D, and cyclophosphamide (VAC), given every 3 weeks for an additional 36 weeks. Results. Of 115 patients evaluable for early response at 12 weeks, 28 (20%) had CR and 66 (43%) had PR. The ultimate CR rate was 52%. Overall, about one-third of patients survived. Prognostic factor analysis revealed that patients < 10 years old (P < 0.001), those with embryonal tumors (P = 0.002), or a GU primary site (P = 0.010), and those who lacked nodal disease (P = 0.041), and those who lacked bone or bone marrow metastasis (P < 0.001) fared better than did others. Conclusions. The 63% CR + PR rate achieved at 12 weeks and overall 5-year FFS seen with this drug pair is similar to that achieved with previously evaluated drug combinations. We conclude that ifosfamide/doxorubicin is highly active in advanced RMS, and should be considered for inclusion in frontline therapy for children with intermediate or highrisk RMS.
AB - Background. The cure rate for children/ adolescents with localized rhabdomyosarcoma (RMS) has tripled over the past 25 years, but patients with metastatic disease at presentation have not benefited similarly, and urgently need new therapy. We evaluated a new drug pair, ifosfamide+doxorubicin, for such patients. Procedure. We estimated the complete and partial response rates (i.e., CR and PR) of 152 previously untreated children/adolescents with metastatic RMS entered on the IRS-IV pilot from July 1988 to October 1991 who received an "up-front window" of ifosfamide (1.8 gm/m2/ day for 5 days) and doxorubicin (30 mg/m2/day for 2 days) given every 3 weeks for 12 weeks. This was followed by combination chemotherapy with vincristine, actinomycin D, and cyclophosphamide (VAC), given every 3 weeks for an additional 36 weeks. Results. Of 115 patients evaluable for early response at 12 weeks, 28 (20%) had CR and 66 (43%) had PR. The ultimate CR rate was 52%. Overall, about one-third of patients survived. Prognostic factor analysis revealed that patients < 10 years old (P < 0.001), those with embryonal tumors (P = 0.002), or a GU primary site (P = 0.010), and those who lacked nodal disease (P = 0.041), and those who lacked bone or bone marrow metastasis (P < 0.001) fared better than did others. Conclusions. The 63% CR + PR rate achieved at 12 weeks and overall 5-year FFS seen with this drug pair is similar to that achieved with previously evaluated drug combinations. We conclude that ifosfamide/doxorubicin is highly active in advanced RMS, and should be considered for inclusion in frontline therapy for children with intermediate or highrisk RMS.
KW - Doxorubicin
KW - IRSG
KW - Ifosfamide
KW - Rhabdomyosarcoma
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U2 - 10.1002/mpo.1227
DO - 10.1002/mpo.1227
M3 - Article
C2 - 11745872
AN - SCOPUS:0034764658
SN - 0098-1532
VL - 37
SP - 442
EP - 448
JO - Medical and Pediatric Oncology
JF - Medical and Pediatric Oncology
IS - 5
ER -