Ifosfamide, carboplatin, and etoposide (ICE) reinduction chemotherapy in a large cohort of children and adolescents with recurrent/refractory sarcoma: The Children's Cancer Group (CCG) experience

Winkle, Patrick Van; Angiolillo, Anne; Krailo, Mark; Cheung, Ying Kuen; Anderson, Barry; Davenport, Virginia; Reaman, Gregory H.; Cairo, Mitchell S.

doi:10.1002/pbc.20227

Cited by 117 publications

(97 citation statements)

References 41 publications

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“…ICE in lower dosages has activity against various solid tumors, [18][19][20][21][22][23][24][25][26][27][28][29][30][31] but it may be particularly suitable for treating NB. Thus, NB is sensitive to all 3 components, whereas other major pediatric solid tumors (eg, Ewing sarcoma) are relatively resistant to platinum compounds.…”

Section: Discussionmentioning

confidence: 99%

“…In Children's Cancer Group studies that used higher dosing than previously reported in children (ifosfamide, 9000 mg/m 2 ; carboplatin, 800 mg/m 2 ; etoposide 500 mg/m 2 ), GM-CSF/interleukin-3 fusion protein, 24 G-CSF, 25 and interleukin-6 plus G-CSF, 26 produced no hematologic benefit; and the large patient population included only 2 cases of NB. 27 The studies pointed to a better response rate of refractory or recurrent sarcomas to this ICE regimen compared with lower dose ICE or 2-drug carboplatin-etoposide or ifosfamide-etoposide regimens. 27 Recently, ICE at dosages higher than in preceding phase 1 studies a) was used as salvage, with major responses in 24/64 (36%) patients treated for primary refractory or progressive NB 28 ; and b) was included in induction regimens for patients with newly diagnosed NB with responses defined according to International Neuroblastoma Response Criteria [29][30][31] (Table 3).…”

Section: Toxicitymentioning

confidence: 95%

“…27 The studies pointed to a better response rate of refractory or recurrent sarcomas to this ICE regimen compared with lower dose ICE or 2-drug carboplatin-etoposide or ifosfamide-etoposide regimens. 27 Recently, ICE at dosages higher than in preceding phase 1 studies a) was used as salvage, with major responses in 24/64 (36%) patients treated for primary refractory or progressive NB 28 ; and b) was included in induction regimens for patients with newly diagnosed NB with responses defined according to International Neuroblastoma Response Criteria [29][30][31] (Table 3). In previously untreated patients, ICE achieved a >70% major response rate.…”

Section: Toxicitymentioning

confidence: 95%

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Ifosfamide, carboplatin, and etoposide for neuroblastoma

Kushner

Modak

Krämer

et al. 2012

Cancer

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BACKGROUND:The authors report a retrospective analysis of high-dose ifosfamide, carboplatin, and etoposide (HD-ICE) for patients with refractory or relapsed neuroblastoma (NB). A major reason for using this regimen was the long time since patients received previous treatment with a platinum compound. The authors also summarized the published experience on ICE in patients with NB. METHODS: Treatment comprised ifosfamide (2000 mg/m 2 daily for 5 days), carboplatin (500 mg/m 2 daily for 2 days), and etoposide (100 mg/m 2 daily for 5 days). Patients who had poor hematologic reserve (platelet count <100,000/lL) from previous therapy received peripheral blood stem cells (PBSCs) after HD-ICE. Disease status before and after HD-ICE was defined according to International Neuroblastoma Response Criteria (expanded to include 123 I-metaiodobenzylguanidine findings). Publications that were informative about ICE for NB were reviewed. RESULTS: Seventy-four patients received 92 cycles of ICE, including 37 patients who received PBSC rescue. Grade 3 toxicities were rare: 1-3 patients had encephalopathy, mucositis, or gastroenteritis. Bacteremia was documented in 24 of 92 cycles (26%). The absolute neutrophil count reached 500/lL on day 17-30 (median, day 22) in patients who had satisfactory hematologic reserve. Disease regressions (major and minor responses) were achieved by 14 of 17 patients (82%) with a new relapse, 13 of 26 patients (50%) with refractory NB, and 12 of 34 patients (35%) who were treated for progressive disease during chemotherapy (P ¼ .005). In the literature, patients received ICE at lower dosages and achieved major response rates >36% in phase 1 and 2 studies (in which less comprehensive staging evaluations were used) that involved resistant NB and >70% in induction for newly diagnosed NB. CONCLUSIONS: HD-ICE is appealing as salvage treatment or consolidative therapy because of its anti-NB activity and the low risk of major nonhematologic toxicity. PBSC support is unnecessary for patients who had intact hematologic reserve.

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Section: Discussionmentioning

confidence: 99%

Section: Toxicitymentioning

confidence: 95%

Section: Toxicitymentioning

confidence: 95%

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Ifosfamide, carboplatin, and etoposide for neuroblastoma

Kushner

Modak

Krämer

et al. 2012

Cancer

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“…In another study, the combined treatment with carbo platin, ifosfamide and etoposide of children and adolescents with recurrent/refractory sarcomas (including 34 patients with HGOS) appeared to be of moderate efficacy, suggesting further exploration of this drug combination in relapsed patients [81].…”

Section: Pharmacogenomics Of Second-line Drugs In Osteosarcoma Reviewmentioning

confidence: 99%

Pharmacogenomics of Second-Line Drugs Used for Treatment of Unresponsive or Relapsed Osteosarcoma Patients

Hattinger¹,

Vella²,

Tavanti³

et al. 2016

Pharmacogenomics

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Second-line treatment of high-grade osteosarcoma (HGOS) patients is based on different approaches and chemotherapy protocols, which are not yet standardized. Although several drugs have been used in HGOS second-line protocols, none of them has provided fully satisfactory results and the role of rescue chemotherapy is not well defined yet. This article focuses on the drugs that have most frequently been used for second-line treatment of HGOS, highlighting the present knowledge on their mechanisms of action and resistance and on gene polymorphisms with possible impact on treatment sensitivity or toxicity. In the near future, validation of the so far identified candidate genetic biomarkers may constitute the basis for tailoring treatment by taking the patients' genetic background into account. Osteosarcoma is the most common tumor of bone, which can exibit different levels of malignancy [1,2]. High-grade osteo sarcoma (HGOS) is a very aggressive neoplasm that, in unselected populations, is responsible for death of approximately 40-50% of patients [2,3]. The subgroup of the so-called conventional HGOS includes patients with high-grade tumors located in the extremities, nonmetastatic at diagnosis and younger than 40 years [1]. In this subgroup of HGOS, prognosis is slightly better, reaching 60-65% when patients are treated with multiagent neoadjuvant chemotherapy [4][5][6].The major clinical problem limiting the cure rate of HGOS patients is relapse, which in most cases consists in development of lung metastasis within the first 24-36 months from diagnosis [7,8]. Treatment of relapsed HGOS is based on different approaches and second-line chemotherapy protocols which, however, are not standardized and can rescue no more than 20-25% of patients [4,5]. Methods of data searching & selectionA systematic literature search was performed using 'treatment' and 'osteosarcoma' as key words in PubMed [9]. We further restricted the selection to studies performed in humans. By using all the aforementioned different combinations and selections, the literature searches revealed a total of 13,976 results. The key terms 'polymorphism', 'toxicity', 'drug response', 'drug resistance', 'pharmaco genetic', 'pharmacogenomic', 'epigenetic', 'methylation' and 'clinical trial' were then used to refine the results of the previous search, in order to select the publications which were strictly related to each section of this review. Full-length articles and reviews in English were taken into consideration.Only drugs used in at least two different clinical trials with published results were included in this review and, consequently, we considered genes and gene poly morphisms with possible relevance for response and/or

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“…Doxorubicin (ADM) has been reported as an active agent against osteosarcoma (Cortes et al, 1972;Cortes et al, 1974). Carboplatin (CBDCA), a platinum-derived agent, has an anti-tumor activity against osteosarcoma (Meyer et al, 2001;Van Winkle et al, 2005;Daw et al, 2011) Cycle I II III IV V VI VII VIII Week 0 3 6 9 12 15 18 21 Day 1 2 3 1 2 3 1 2 3 1 2 3 1 2 3 1 2 3 1 2 3 1 2 …”

Section: Introductionmentioning

confidence: 99%

Carboplatin and Doxorubicin in Treatment of Pediatric Osteosarcoma: A 9-year Single Institute Experience in the Northern Region of Thailand

Choeyprasert¹,

Natesirinilkul²,

Charoenkwan³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: Osteosarcoma is the most common primary bone tumor in childhood and adolescence. Carboplatin, a platinum-derived agent, is used as neoadjuvant chemotherapy for pediatric osteosarcoma because of its anti-tumor activity and had low toxicity as compared to cisplatin. Objective: To determine demographic data, prognostic factors and outcome of childhood osteosarcoma treated with a carboplatin-based chemotherapeutic protocol at Chiang Mai University. Method: A retrospective analysis was conducted on 34 osteosarcoma patients aged less than 18 years and treated between 2003 and 2011. Results: Overall limb-salvage and amputation rates were 23.5% and 70.6%, respectively. With the mean follow-up time of 29.5 months (1.5-108.9), the Kaplan-Meier analysis for 3-year disease-free survival (DFS) and 3-year overall survival (OS) were 20.2±7.7% and 47.1±9.5% respectively. Patients who had initial pulmonary metastasis were at significantly greater risk for developing recurrence (p=0.02, OR=7; 1.2-40.1) and had a tendency to have lower 3-year OS compared to those without initial pulmonary metastasis (28.1±13%, 63.1±12.3%, respectively, p=0.202). On univariate analysis, age at diagnosis >14 years and patients who were declined surgery were significantly associated with lower 3-year OS (p=0.008 and <0.05, respectively). However, age at diagnosis, sex, tumor size and histological subtypes were not found to significantly affect recurrence or survival. Conclusions: In our study, the survival rate was far lower than those reported from developed countries. These might indicate the ineffectiveness of carboplatin in combination with doxorubicin as frontline treatment of pediatric osteosarcoma, especially in those with initial pulmonary metastasis. Refinement in risk and treatment stratification and dose intensification for pediatric osteosarcoma constitutes a future challenge to improve outcomes, especially in metastatic patients who may need a more intensive regimen.

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Ifosfamide, carboplatin, and etoposide (ICE) reinduction chemotherapy in a large cohort of children and adolescents with recurrent/refractory sarcoma: The Children's Cancer Group (CCG) experience

Abstract: The ORR to ICE reinduction chemotherapy in children with recurrent/refractory sarcoma was 51%. OS of 1 and 2 years appeared significantly improved in patients who had CR or PR following ICE reinduction therapy or who had rhabdomyosarcoma with embryonal histology.

Cited by 117 publications

References 41 publications

Ifosfamide, carboplatin, and etoposide for neuroblastoma

Ifosfamide, carboplatin, and etoposide for neuroblastoma

Pharmacogenomics of Second-Line Drugs Used for Treatment of Unresponsive or Relapsed Osteosarcoma Patients

Carboplatin and Doxorubicin in Treatment of Pediatric Osteosarcoma: A 9-year Single Institute Experience in the Northern Region of Thailand

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