Ifosfamide/etoposide combination in the treatment of recurrent malignant solid tumors of childhood. A pediatric oncology group phase II study

Abstract

Background. The prognosis for children with recurrent or resistant malignant solid tumors remains dismal. More effective rescue therapy is needed for these children. Methods. Between August 1987 and November 1990, 311 children with recurrent or resistant malignant solid tumors were treated by investigators in the Pediatric Oncology Group with intravenous infusions of 2.0 g/m2 of ifosfamide and 100 mg/m2 of etoposide (VP‐16) plus mesna as uroprotection three times daily, with courses being repeated every 14–21 days for as long as the patients responded to therapy. Results. Seventy‐four percent of the 294 assessable patients entered in the study had metastatic disease and previously had been treated heavily. The complete response/partial response rate was 30%, and the overall response rate was 39.5%. Toxic effects included nephrotoxicity, mild liver dysfunction, neurotoxicity, and myelosuppression. Sixty‐eight percent had an absolute neutrophil count (ANC) of less than 500/μl. In 1606 courses of therapy administered, only 3.6% of patients developed a bacterial infection. Only two patients died of gram‐negative sepsis. Four percent of the patients had gross hematuria (> 50 erythrocytes/high‐power field), and 18.5% had microscopic hematuria (< 20 erythrocytes/high‐power field). Fanconi syndrome developed in eight children. Conclusions. Ifosfamide/VP‐16 is an active combination in children with recurrent malignant solid tumors. Although it was myelosuppressive, the incidence of infection was quite low (3.6%). Mesna was very effective in preventing the development of hematuria.

Mifamurtide for the treatment of nonmetastatic osteosarcoma

“…There are currently four chemotherapeutic agents, which consist of doxorubicin, cisplatin, high-dose methotrexate with leucovorin rescue, and ifosfamide [7][8][9][10][11]. Vigorous chemotherapy treatment with these agents has significantly improved survival of the osteosarcoma patients over the past several decades [12].…”

Clinical Study on Carboplatin for Treating Pediatric Patients with Wilms Tumors

“…Further, three-agent regimens containing carboplatin, e.g. the use of ICE for patients in this setting is associated with a response rate of 71% (Kung et al, 1993;Kung et al, 1995). The use of high-dose chemotherapy followed by autologous stem cell transplantation may be effective in salvaging patients with relapsed WT and poor prognostic features.…”

“…It was reported that the response rate of children with relapsed or resistant WT to a combination of carboplatin, ifosfamide, and etoposide, at the maximal tolerated dose of 635 mg/m 2 for carboplatin, is associated with a CR rate of 32% and a total response rate of 63% (Kung et al, 1993;Kung et al, 1995). In the field of cancer chemotherapy including in the treatment of WT, carboplatin is a common choice (Akkuzu et al, 2013;Bag et al, 2013;Butthongkomvong et al, 2013;Fu et al, 2013;Khemapech et al, 2013;Kucukoztas et al, 2013;Natukula et al, 2013;Oranratanaphan et al, 2013;Ozdemir et al, 2013;Zhang et al, 2013;Pitakkarnkul et al, 2013).…”

High histologic and overall response to dose intensification of ifosfamide, carboplatin, and etoposide with cyclophosphamide, doxorubicin, and vincristine in patients with high‐risk ewing sarcoma family tumors

“…The Pediatric Oncology Group reported an overall response rate of 43% (23% in ES) in 92 pediatric patients after administering ICE in a 3-day schedule. 36 Marina et al 37 tested carboplatin in association with ifosfamide at a dose of 2 g/m 2 for 2 days and etoposide at a dose of 100 mg/m 2 for 2 days and reported an area under the curve for carboplatin of 8 mg/mL per minute: Although their regimen produced a low CR rate, they reported approximately 33% major responses among patients with neuroblastoma, rhabdomyosarcoma, and ESFT. Our decision to use the ICE regimen in a 5-day schedule at maximum dosage derived from the report from Cairo et al, 25 who treated 123 patients with refractory or recurrent pediatric solid tumors and obtained a 63% overall response rate and 50% major response rate among patients with soft tissue sarcomas and ES.…”