Phase II trial of first-line high-dose ifosfamide in advanced soft tissue sarcomas of the adult: A study of the Spanish Group for Research on Sarcomas (GEIS)

Buesa, J. M.; López‐Pousa, Antonio; Martín, Javier; Antón, A.; Muro, Javier García del; Bellmunt, J; Arranz, F.; Valentí, V.; Escudero, P.; Menéndez, D; Casado, Antonio; Poveda, Andrés

doi:10.1023/a:1008474802882

Cited by 61 publications

(46 citation statements)

References 20 publications

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“…Response rates to ifosfamide, however, have been observed to range from 20% to 60% in single-institution series in which higher-dose regimens or combination treatment with doxorubicin has been used. [62][63][64][65][66] A major deterrent to the use of adjuvant chemotherapy has been the risk of its causing adverse toxic effects in patients who do not otherwise respond to therapy. With the advent of growth factors such as granulocyte colony-stimulating factor and granulocyte-macrophage colonystimulating factor, the morbidity related to neutropenia has been minimized; however, doselimiting thrombocytopenia continues to pose a challenge in the treatment of patients with chemotherapy.…”

Section: Systemic Therapymentioning

confidence: 99%

Soft Tissue Sarcomas

Cormier

Pollock

2004

CA: A Cancer Journal for Clinicians

503

345

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Sarcomas are a heterogeneous group of rare tumors that arise predominantly from the embryonic mesoderm. They present most commonly as an asymptomatic mass originating in an extremity but can occur anywhere in the body, particularly the trunk, retroperitoneum, or the head and neck. Pretreatment radiologic imaging is critical for defining the local extent of a tumor, staging the disease, guiding biopsies, and aiding in diagnosis. Core-needle biopsy is the preferred biopsy technique for diagnosing soft tissue sarcomas. The American Joint Committee on Cancer (AJCC) staging system for soft tissue sarcomas is based on histologic grade, the tumor size and depth, and the presence of distant or nodal metastases.Despite improvements in local control rates with wide local resections and radiation therapy, metastasis and death remain a significant problem in 50% of patients who present with high-risk soft tissue sarcomas. The most common site of metastasis is the lungs, and metastasis generally occurs within two to three years after the completion of therapy. Progress in the molecular characteristics of these tumors should in the near future translate into molecularly based therapies that can be incorporated into standard treatment strategies. (CA Cancer J Clin 2004;54:94 -109.) © American Cancer Society, 2004.

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Section: Systemic Therapymentioning

confidence: 99%

Soft Tissue Sarcomas

Cormier

Pollock

2004

CA: A Cancer Journal for Clinicians

503

345

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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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“…This treatment was accompanied by grade 3 or 4 hematological and nonhematological toxicity to an extent that was deemed unacceptable, while there was no clear enhancement in antitumor activity. The disadvantageous therapeutic index of ifosfamide at higher doses was underscored in several other studies [64,65].…”

Section: Ifosfamide Monotherapymentioning

confidence: 95%

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

et al. 2007

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After completing this course, the reader will be able to:1. Describe the current role of ifosfamide in the treatment of soft tissue sarcomas in adult patients.2. Discuss factors that may affect ifosfamide metabolism and its therapeutic index.3. Explain the advantages of ifosfamide over doxorubicin in the context of new treatment combinations.4. Discuss strategies to improve survival outcome in patients with soft tissue sarcoma.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACTThe treatment outcome of patients with locally advanced and metastatic soft tissue sarcomas is poor. Doxorubicin is regarded as standard treatment, but its use is featured by the occurrence of cardiotoxicity. This hinders the administration of this drug at high doses or in combination with, in theory, attractive newly developed targeted drugs, such as vascular endothelial growth factor (VEGF) pathway inhibitors. The combination of doxorubicin and VEGF pathway inhibitors has been shown to yield an unacceptable high rate of cardiomyopathy. Ifosfamide is the only drug that consistently shows response rates comparable to those of doxorubicin. The lack of cardiotoxicity renders this drug a much more attractive alternative than doxorubicin to be explored at high doses or as part of new drug combinations. This review addresses the clinical pharmacology, metabolism, and present role of ifosfamide in the treatment of locally advanced and/or metastatic soft tissue sarcomas, excluding gastrointestinal stromal tumors, the Ewing-like sarcomas, and other small blue round cell tumors. Furthermore, this review focuses on the anticipated growing role of ifosfamide in the development of new treatment strategies. The Oncologist 2007;

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Phase II trial of first-line high-dose ifosfamide in advanced soft tissue sarcomas of the adult: A study of the Spanish Group for Research on Sarcomas (GEIS)

Abstract: HDI is an active drug in first-line therapy against adult STS. Different administration schedules should be evaluated in an attempt to improve its therapeutic index.

Cited by 61 publications

References 20 publications

Soft Tissue Sarcomas

Soft Tissue Sarcomas

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

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

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