Ifosfamide/Carboplatin/Etoposide (ICE) for Recurrent Malignant Solid Tumors of Childhood

Kung, Faith; Desai, Shaili; Dickerman, Joseph D.; Goorin, Allen M.; Harris, MB; Inoue, Shuhei; Krischer, Jeffrey P.; Murphy, S.; Pratt, Charles B.; Toledano, Stuart

doi:10.1097/00043426-199508000-00009

Cited by 64 publications

(51 citation statements)

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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%

“…Comparisons of response rates between HD-ICE versus lower dose ICE regimens in published reports are of limited value, because the latter do not specify whether patients underwent BM tests and MIBG scans. 18,[20][21][22][23] We previously reported that response to salvage chemotherapy is significantly more likely in patients with NB who are treated for a new relapse that occurs off therapy than in patients who are treated for NB that is persistent (ie, refractory) or progressing on treatment. 9 Results with HD-ICE are consistent with that observation as regards major responses (CR/VGPR/PR; P < .0005) as well as disease regressions overall (major responses and MRs; P ¼ .005).…”

Section: Discussionmentioning

confidence: 99%

“…Literature Review: Ifosfamide, Carboplatin, and Etoposide for Neuroblastoma Pediatric phase 1 trials of ICE [18][19][20][21] were based on promising antitumor activity and tolerable toxicity of each agent and the antitumor synergism of carboplatin plus Abbreviations: AE, with or without; AUC, area under the curve (mg minute/mL); CR, complete response; GM-CSF, granulocyte-colony-stimulating factor; NB, neuroblastoma; NS, not specified; PR, partial response; VGPR, very good partial remission.…”

Section: Toxicitymentioning

confidence: 99%

“…Similar encouraging results were seen in the Pediatric Oncology Group experience, first, with a phase 1 trial that also investigated carboplatin dose escalation with fixed dosing of ifosfamide plus etoposide and, subsequently, with a phase 2 trial of ifosfamide 6000 mg/m 2 , carboplatin 635 mg/m 2 , and etoposide 300 mg/m 2 . 20 That dosing was used in a phase 1 study of amifostine, but this chemoprotectant caused grade 3 and 4 toxicities. 23 The studies described above did not specify whether NB responses included MIBG scans or BM findings.…”

Section: Toxicitymentioning

confidence: 99%

“…Second, the combination's lack of cardiotoxicity, hepatotoxicity, and gastrointestinal toxicity is appealing, and there is little risk of undue morbidity (eg, mucositis or nephrotoxicity). [12][13][14] Third, ototoxicity is a concern in this patient population, but hearing is minimally affected by carboplatin in nonmyeloablative doses. Finally, risks from myelosuppression were deemed acceptable with a) standard supportive measures in patients who have adequate bone marrow (BM) reserve, or b) infusion of peripheral blood stem cells (PBSCs) in patients who have poor hematologic reserve because of prior therapy.…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Toxicitymentioning

confidence: 99%

Section: Toxicitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ifosfamide, carboplatin, and etoposide for neuroblastoma

Kushner

Modak

Krämer

et al. 2012

Cancer

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Medication Development and Testing in Children and Adolescents

Vitiello

Jensen

1997

Arch Gen Psychiatry

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Progress in pediatric psychopharmacological research has suffered notable delay, especially compared with the achievements in adult psychopharmacology. Although safety and efficacy of the use of many psychotropic agents in children remain largely unproved, their pediatric use has been increasing and their widespread off-label prescribing by practitioners has raised some important concerns. The National Institute of Mental Health, in cooperation with the Food and Drug Administration and leading researchers, has coordinated systematic efforts to identify the major obstacles to research in pediatric psychopharmacology and to propose feasible solutions. In 1995, a conference cosponsored by the national Institute of Mental Health and the Food and Drug Administration gathered more than 100 research experts, family and patient advocates, and representatives of mental health professional associations. Participants met in working groups focused on specific aspects of child research and reached consensus on various recommendations. Each of the various aspects relevant to conducting research in this area (methodological, ethical, legal, regulatory, financial, and family or community context) presents specific challenges, which are herein outlined. Recommendations for possible solutions are presented, some of which are being implemented. Because data about drug safety and efficacy in adults can rarely be extrapolated to children, there is no substitute for pediatric psychopharmacological research. Successful strategies for overcoming the many obstacles with which this research has to contend must enlist the concerted efforts of all the relevant parties (investigators, clinicians, industry, federal agencies, ethicists, families, and community representatives).

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