Phase I trial of a twice-daily regimen of amifostine with ifosfamide, carboplatin, and etoposide chemotherapy in children with refractory carcinoma

Fouladi, Maryam; Stempak, Diana; Gammon, R N Janet; Klein, Julia; Grant, Ron; Greenberg, Mark; Koren, Gideon; Baruchel, Sylvain

doi:10.1002/1097-0142(20010815)92:4<914::aid-cncr1401>3.0.co;2-s

Cited by 23 publications

(16 citation statements)

References 27 publications

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“…Antioxidant agents like amifostine, a thiol antioxidant, have cytoprotective action against platinuminduced renal toxicity. However, amifostine is not used due to its toxic effects: hypocalcaemia, anxiety, and hypotension [12].…”

Section: Introductionmentioning

confidence: 99%

Seleno l-Methionine Acts on Cyclophosphamide-Induced Kidney Toxicity

Ayhancı

Güneş

Şahıntürk

et al. 2009

Biol Trace Elem Res

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The anticancer drug cyclophosphamide (CP) has nephrotoxic effects besides its urotoxicity, which both in turn limit its clinical utility. The nephrotoxicity of CP is less common compared to its urotoxicity, and not much importance has been given for the study of mechanism of CP-induced nephrotoxicity so far. Overproduction of reactive oxygen species (ROS) during inflammation is one of the reasons of the kidney injury. Selenoproteins play crucial roles in regulating ROS and redox status in nearly all tissues; therefore, in this study, the nephrotoxicity of CP and the possible protective effects of seleno L-methionine (SLM) on rat kidneys were investigated. Forty-two Sprague-Dawley rats were equally divided into six groups of seven rats each. The control group received saline, and other rats were injected with CP (100 mg/kg), SLM (0.5 or 1 mg/kg), or CP+ SLM intraperitoneally. Malondialdehyde (MDA) and glutathione (GSH) levels in kidney homogenates of rats were measured, and kidney tissues were examined under the microscope. CP-treated rats showed a depletion of renal GSH levels (28% of control), while CP+SLM-injected rats had GSH values close to the control group. MDA levels increased 36% of control following CP administration, which were significantly decreased after SLM treatment. Furthermore, these biochemical results were supported by microscopical observations. In conclusion, the present study not only points to the therapeutic potential of SLM in CP-induced kidney toxicity but also indicates a significant role for ROS and their relation to kidney dysfunction.

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Section: Introductionmentioning

confidence: 99%

Seleno l-Methionine Acts on Cyclophosphamide-Induced Kidney Toxicity

Ayhancı

Güneş

Şahıntürk

et al. 2009

Biol Trace Elem Res

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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%

“…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. 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.…”

Section: Toxicitymentioning

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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“…These conflicting findings may be related to differences in the schedule and dosage of amifostine, inadequate statistical power, and differences in the underlying chemotherapy and patient populations studied. Fouladi and colleagues conducted a phase 1 evaluation of amifostine in combination with a 6 hour cisplatin infusion and concluded the optimum schedule was 600 mg/m 2 just prior to and 3 hours into a 6 hour cisplatin infusion (14). This schedule of administration significantly reduced the ototoxicity associated with the treatment of medulloblastoma (5).…”

Section: Introductionmentioning

confidence: 99%

Clinical Pharmacokinetics of Amifostine and WR1065 in Pediatric Patients with Medulloblastoma

McKibbin

Panetta

Fouladi

et al. 2010

Clinical Cancer Research

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Purpose: We evaluated the pharmacokinetics of amifostine and WR1065 in pediatric patients with newly diagnosed medulloblastoma to assess the influence of patient covariates, including demographics, clinical characteristics, and genetic polymorphisms, on amifostine and WR1065 pharmacokinetic parameters.Experimental Design: We assessed the pharmacokinetics of amifostine and WR1065 in 33 children who received amifostine (1-minute infusion, 600 mg/m 2 ) just before the start of and 3 hours into a 6-hour cisplatin infusion. Serial blood samples were collected after doses 1 (0 hour) and 2 (3 hours) of course 1. Amifostine and WR1065 were quantitated by high performance liquid chromatography with electrochemical detection. A pharmacokinetic model was simultaneously fit to amifostine and WR1065 plasma or whole blood concentration-versus-time data. The influence of demographic, biochemical, and pharmacogenetic covariates on amifostine and WR1065 disposition was evaluated.Results: Body surface area was the primary size-based covariate for amifostine pharmacokinetics explaining 53% and 56% of interindividual variability in plasma and whole-blood amifostine clearance, respectively. , and 12.5 L/h/m 2 . Conclusions: These results support using body surface area for calculating doses of amifostine in children. Similar to data in adults, amifostine and WR1065 are rapidly cleared from plasma and whole blood in children.

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Phase I trial of a twice-daily regimen of amifostine with ifosfamide, carboplatin, and etoposide chemotherapy in children with refractory carcinoma

Cited by 23 publications

References 27 publications

Seleno l-Methionine Acts on Cyclophosphamide-Induced Kidney Toxicity

Seleno l-Methionine Acts on Cyclophosphamide-Induced Kidney Toxicity

Ifosfamide, carboplatin, and etoposide for neuroblastoma

Clinical Pharmacokinetics of Amifostine and WR1065 in Pediatric Patients with Medulloblastoma

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