The Pharmacologic Basis of Ifosfamide Use in Adult Patients with Advanced Soft Tissue Sarcomas

Tascilar, Metin; Loos, Walter J.; Seynaeve, C.; Verweij, Jaap; Sleijfer, Stefan

doi:10.1634/theoncologist.12-11-1351

Cited by 73 publications

(47 citation statements)

References 71 publications

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“…The disease control rate in leiomyosarcoma patients (40%) was lower than in patients with other histologic types. Synovial sarcoma in particular is thought to be highly sensitive to ifosfamide; however, this is based merely on a small series of patients, while randomized data are lacking [4,9,19]. In the present study of 5 patients with synovial sarcoma, tumor response was achieved in 4 (80%).…”

Section: Discussionmentioning

confidence: 60%

“…Of the chemotherapeutic agents that have been used to treat STS, the two most commonly used currently are doxorubicin and ifosfamide [2]. Doxorubicin, known as the most active agent, has been shown to induce a varied range of response rates (16–27%), and has remained the treatment of choice for patients with advanced STS [3,4]. Unfortunately, the use of doxorubicin is limited due to cumulative cardiotoxicity.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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: Discussionmentioning

confidence: 60%

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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“…With the exceptions of rhabdomyosarcomas and soft part Ewing sarcomas, systemic chemotherapy for the different STS subtypes is based on doxorubicin and ifosfamide, which remain the cornerstone first-line treatment in 2010. 10,11 In recent years, however, the insight has emerged that systemic therapy should become more tailored, and particularly for STS, according to histologic subtype. This approach is illustrated clearly by the relevant activity of imatinib in advanced dermatofibrosarcoma protuberans, 12,13 paclitaxel in angiosarcoma, 14,15 gemcitabine in leiomyosarcomas, 16,17 trabectedin in patients with myxoid/round cell liposarcomas, 18 and of mammalian target of rapamycin inhibitors in perivascular epithelioid cell tumors.…”

Section: Discussionmentioning

confidence: 99%

Trends in survival for patients with metastatic soft‐tissue sarcoma

Italiano

Mathoulin‐Pélissier²,

Cesne

et al. 2010

Cancer

259

179

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BACKGROUND:The objective of this study was to determine whether the overall survival of patients with metastatic soft tissue sarcoma (STS) has improved over the last 20 years. METHODS: In total, 1024 patients who had synchronous metastatic ( RESULTS:The proportion of patients with SM, the interval between diagnosis and MM, and the clinical characteristics of the patients were similar across the 4 periods. Although there was no significant difference in the median overall survival (OS) from P1 through P2 (P1, 12.3 months; 95% confidence interval [CI], 9.9-14.7 months; P2, 11.4 months; 95% CI, 9-13.9 months), significant improvements were observed in the later periods (P3, 15 months; 95% CI, 11.8-18.2 months; P4, 18 months; 95% CI, 15.3-20.7 months; P ¼ .029; log-rank test). The 2-year OS rate also increased throughout the study period from 28.1% during P1 to 38.7% during P4. On multivariate analysis, period of diagnosis, age, histologic subtype, time to metastatic recurrence, French Federation of Cancer Centers Sarcoma Group grade, and the number of metastatic sites were independent prognostic factors for OS. CONCLUSIONS: The current analysis revealed that the median OS of patients with metastatic STS had improved by 50% during the last 20 years. These data should be considered in the interpretation of results from ongoing and future STS trials.

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“…5,6 Ifosfamide, an alkylating agent, in combination with cisplatin and etoposide (VIP) increased median OS to 9 months compared with 7.3 months with cisplatin and etoposide alone. In addition, the 2-year OS was improved from 5% to 13% in favor of VIP.…”

Section: Introductionmentioning

confidence: 99%

“…Ifosfamide is a prodrug whose cytotoxic effects are largely exerted by its active metabolite isophosphoramide mustard. 6 However, the clinical utility of ifosfamide is limited by a number of toxic metabolites such as acrolein and chloracetaldehyde, which are associated with hemorrhagic cystitis and neurotoxicity, respectively. Palifosfamide (Zymafos, ZIO-201; ZIOPHARM Oncology, Boston, MA) is a salt formulation of isophosphoramide mustard, the active metabolite of ifosfamide that was developed by ZIO-PHARM Oncology.…”

Section: Introductionmentioning

confidence: 99%

Carboplatin and Etoposide With or Without Palifosfamide in Untreated Extensive-Stage Small-Cell Lung Cancer: A Multicenter, Adaptive, Randomized Phase III Study (MATISSE)

Jalal

Lavin²,

et al. 2017

JCO

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To evaluate the efficacy of the addition of palifosfamide to carboplatin and etoposide in extensive stage (ES) small-cell lung cancer (SCLC). Patients and MethodsMATISSE was a randomized, open-label, adaptive phase III study. Previously untreated patients with ES SCLC were randomly assigned in a 1:1 fashion to receive carboplatin at area under the serum concentration-time curve 5 on day 1 plus etoposide 100 mg/m 2 per day on days 1 to 3 every 21 days (CE) or carboplatin at area under the serum concentration-time curve 4 on day 1 plus etoposide 100 mg/m 2 per day plus palifosfamide 130 mg/m 2 per day on days 1 to 3 every 21 days (PaCE). The primary end point was overall survival. ResultsIn all, 188 patients were enrolled; 94 patients received CE and 94 patients received PaCE. The median age on both arms was 61 years. Six cycles of chemotherapy were completed on both arms of the study by approximately 50% of the patients. Serious adverse events were documented and did not differ significantly between patients receiving PaCE and those receiving CE. Median overall survival was similar between both arms with 10.03 months on PaCE and 10.37 months on CE (P = .096). ConclusionThe addition of palifosfamide to CE failed to improve survival in ES SCLC.

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The Pharmacologic Basis of Ifosfamide Use in Adult Patients with Advanced Soft Tissue Sarcomas

Cited by 73 publications

References 71 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

Trends in survival for patients with metastatic soft‐tissue sarcoma

Carboplatin and Etoposide With or Without Palifosfamide in Untreated Extensive-Stage Small-Cell Lung Cancer: A Multicenter, Adaptive, Randomized Phase III Study (MATISSE)

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