High-dose ifosfamide plus adriamycin in the treatment of adult advanced soft tissue sarcomas: Is it feasible?

Pas, Tommaso De; Braud, Filippo de; Orlando, Luis; Nolè, F.; Munzone, Elisabetta; Zampino, M. G.; Fazio, Nicola; Aapro, Matti; Goldhirsch, A.

doi:10.1023/a:1008311901856

Cited by 37 publications

(20 citation statements)

References 5 publications

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“…Ifosfamide, a prodrug that is metabolized in the liver to the active alkylating agent, has provided single-agent activity in patients with pretreated advanced STS [5,6,7]. Several phase II studies with high-dose ifosfamide (HDI), ranging from 12 to 18 g/m 2 , have reported significantly higher response rates, even in patients previously treated with ifosfamide [6,8,9]. A few other chemotherapeutic agents have shown less antitumor activity.…”

Section: Introductionmentioning

confidence: 99%

High-Dose Ifosfamide as Second- or Third-Line Chemotherapy in Refractory Bone and Soft Tissue Sarcoma Patients

et al. 2011

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Introduction: For patients with refractory bone and soft tissue sarcoma (STS), treatment options have been limited. Ifosfamide is an alkylating agent with well-demonstrated efficacy against STS, and dose-dependent activity. The aim of this retrospective study was to evaluate the response rate, progression-free survival (PFS), progression-free rate (PFR), and median duration of response to high-dose ifosfamide (HDI) as at least second-line chemotherapy for patients with advanced bone sarcoma and STS. Patients and Methods: Thirty metastatic, unresectable sarcoma patients who were treated with HDI chemotherapy between May 1999 and November 2007 were included in the analysis. In total, 106 cycles (median 3 cycles; range 1–8 cycles) were administered. Twenty-one patients received treatment as second-line chemotherapy, and 9 patients as third-line treatment. HDI was given at a dose of 2 g/m² over 3 h, and at a dose of 2 g/m² per day; continuous infusion was administered on 6 consecutive days (2 g/m²/6 days) every 3 weeks. Results: After a median follow-up of 49 months (range 10–114), median PFS was 2.9 months (range 0.4–9.3) and median overall survival 8.7 months (range 0.4–57.8). The 3- and 6-month PFR were 47% (SE 9.1%) and 20% (SE 7.3%), respectively. Median response duration of HDI was 2.9 months (range 0.7–7.6). Of the 28 evaluable patients, 2 (7%) achieved complete response, 5 (18%) partial response, and 4 (14%) stable disease, and overall disease control was 39%. Two responders out of 7 (28.5%) and 4 patients out of 11 (36%) with controlled disease by HDI had a synovial sarcoma. Two patients were not evaluable because they were switched to another treatment due to ifosfamide-induced encephalopathy. Grade 3–4 neutropenia was seen in 13 (43%) patients, and treatment-related death was observed in one patient. Conclusion: HDI at a total dose of 14 g/m² with mesna is still an active salvage regimen, particularly in patients with synovial sarcomas.

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Section: Introductionmentioning

confidence: 99%

High-Dose Ifosfamide as Second- or Third-Line Chemotherapy in Refractory Bone and Soft Tissue Sarcoma Patients

et al. 2011

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“…High-dose ifosfamide is generally given in a 4-to 5-day infusion, however, and is usually associated with severe neutropenia [21][22][23][24][25]. This side-effect must be taken into account, particularly when treating relapsing patients, whose quality of life is an important goal.…”

Section: Introductionmentioning

confidence: 99%

Prolonged 14‐day continuous infusion of high‐dose ifosfamide with an external portable pump: Feasibility and efficacy in refractory pediatric sarcoma

Meazza

Casanova

Luksch

et al. 2010

Pediatric Blood & Cancer

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BackgroundIfosfamide is currently used to treat pediatric sarcomas and increasing its dosage may be associated with a better response rate. Prolonged continuous infusion seems an attractive administration modality.MethodsIfosfamide 14 g/m2 (with mesna 14 g/m2) was administered through an ambulatory portable pump over 14 days as a continuous infusion, starting every 3 weeks, in 14 patients with relapsing sarcomas. No growth factors were given.ResultsAcute grade 3 hematological toxicity was observed in only 13/66 cycles and red cell transfusions were given in two patients. Hematuria and dysuria occurred in three cases. The response rate was: five partial responses, five stable disease. The median time to progression was 3 months (range: 2–19 months). The best response rate was seen for synovial sarcoma and Ewing sarcoma.ConclusionProlonged 14‐day continuous infusion of high‐dose ifosfamide is well tolerated. Potentially interesting preliminary responses in pediatric patients already treated with ifosfamide are reported. Pediatr Blood Cancer. 2010;55:617–620. © 2010 Wiley‐Liss, Inc.

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“…Although response rates did appear to be somewhat higher with combination chemotherapy, this did not translate into prolongation of time to progression (TTP) or OS, and came at the expense of greater toxicity (Table 1) [15][16][17][18]. Subsequent small phase II studies then sought to dose intensify by use of colony stimulated factors, using doses of doxorubicin of 60-90 mg/m 2 , and ifosfamide 10-12.5 g/m 2 , achieving increased ORR of 50-66% [19][20][21]. These studies demonstrated…”

Section: Combination Chemotherapymentioning

confidence: 99%

First-line treatment in advanced or metastatic disease: one size fits all or adapted to specific histiotypes?

Seddon

2016

Current Opinion in Oncology

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High-dose ifosfamide plus adriamycin in the treatment of adult advanced soft tissue sarcomas: Is it feasible?

Abstract: While feasible, this regimen showed heavy toxicity. Nevertheless, 74% of the patients were able to complete the planned treatment. Adjustment of the schedule of IFO continuous infusion to improve this combination is currently under investigation.

Cited by 37 publications

References 5 publications

High-Dose Ifosfamide as Second- or Third-Line Chemotherapy in Refractory Bone and Soft Tissue Sarcoma Patients

High-Dose Ifosfamide as Second- or Third-Line Chemotherapy in Refractory Bone and Soft Tissue Sarcoma Patients

Prolonged 14‐day continuous infusion of high‐dose ifosfamide with an external portable pump: Feasibility and efficacy in refractory pediatric sarcoma

First-line treatment in advanced or metastatic disease: one size fits all or adapted to specific histiotypes?

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