scholarly journals OTHR-16. CONCURRENT USE OF APREPITANT AND IFOSFAMIDE IN PEDIATRIC CANCER PATIENTS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii424-iii424
Author(s):  
Shelby Winzent ◽  
Nathan Dahl ◽  
Molly Hemenway ◽  
Rachel Lovria ◽  
Kathleen Dorris
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
Hepatic Metabolism ◽  
High Dose ◽  
Tumor Type ◽  
Age Related ◽  
Concurrent Use ◽  
Pediatric Cancer Patients ◽  
Nongerminomatous Germ Cell Tumor ◽  
Neurokinin 1

Abstract BACKGROUND Aprepitant, a selective neurokinin-1 receptor antagonist, is commonly used for prevention of chemotherapy-induced nausea and vomiting. Its use with ifosfamide is controversial due to the putative risk of potentiating neurotoxicity via inhibition of cytochrome P450 3A4 (CYP3A4). The current literature examining this interaction is inconclusive, and little data exists in pediatrics. We seek to describe a single-institution experience with concurrent aprepitant and ifosfamide administration. METHODS A retrospective review of patients treated with ifosfamide and aprepitant from 2009–2018 was conducted. Data collected included demographics, tumor type, number of days of concurrent therapy, dosing, and documented of neurotoxicity. RESULTS Twenty patients aged 7–21 years (median 17 years) were identified. Diagnoses included thirteen sarcomas and seven CNS tumors (6 germ cell tumors; 1 intracranial sarcoma). Five patients received high dose ifosfamide (>2,000mg/m2/day). The number of concurrent ifosfamide and aprepitant doses ranged from 2–18 (median, 8.5). Only one patient (5%) developed ifosfamide-induced neurotoxicity: a 7-year-old female with a nongerminomatous germ cell tumor who presented with seizures and somnolence. She received methylene blue and returned to her neurologic baseline. She completed her ifosfamide course without incident. She was the only patient to require weight-based aprepitant dosing and to receive the liquid formulation. CONCLUSIONS Aprepitant should be used with caution when administered concurrently with ifosfamide due to the risk of neurotoxicity. However, the incidence of neurotoxicity in this retrospective pediatric cohort was low. This interaction may be more significant in younger patients due to age-related differences in hepatic metabolism, but further study is required.

scholarly journals Second-line high-dose chemotherapy in patients with mediastinal and retroperitoneal primary non-seminomatous germ cell tumors: the EBMT experience

2005 ◽  
Vol 16 (1) ◽  
pp. 146-151 ◽  
Author(s):  
U. De Giorgi ◽  
T. Demirer ◽  
H. Wandt ◽  
C. Taverna ◽  
W. Siegert ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Second Line

High-Dose Chemotherapy for Recurrent Ovarian Germ Cell Tumors

2015 ◽  
Vol 33 (2) ◽  
pp. 226-227 ◽  
Author(s):  
Natraj Reddy Ammakkanavar ◽  
Daniela Matei ◽  
Rafat Abonour ◽  
Lawrence H. Einhorn
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
High Dose Chemotherapy ◽  
High Dose

scholarly journals Testicular tumors

2011 ◽  
pp. 28-35
Author(s):  
Giovanni Rosti ◽  
Ornella Carminati ◽  
Claudia Casanova ◽  
Giorgio Papiani
Keyword(s):  
Germ Cell ◽  
Residual Disease ◽  
Clinical Stage ◽  
Germ Cell Tumors ◽  
Stage I ◽  
Prognostic Scores ◽  
Retroperitoneal Lymph Node Dissection ◽  
High Dose ◽  
Advanced Phase ◽  
Response To Chemotherapy

Germ cell tumors of the testes represent a unique paradigm of diseases which can be cured even in extremely advanced phase. Unfortunately, this makes them unique among adult solid tumors. Seminoma and non seminoma are relatively rare with approximatively 25,000 patients in Europe per year, but numbers are increasing world wide. Different strategies are needed depending on stage and prognostic scores. Seminoma is extremely sensitive to radiation therapy and chemotherapy, while all germ cell tumors show a very good response to chemotherapy. Clinical stage I seminoma is currently treated with radiation, single course carboplatin or surveillance policy. Clinical stage I non seminoma can also be approached with different strategies such as retroperitoneal lymph node dissection, observation or one-two courses of standard chemotherapy. Stage II seminoma may be treated with either radiation or chemotherapy, while for all advanced stages chemotherapy is mandatory. Since the mid-eighties PEB (Cisplatin, Etoposide and Bleomycin) is the regimen of choice and no other schedule has proved superior in terms of efficacy. Surgery on the residual disease is crucial to the whole strategy and should be performed or attempted in all cases. Consequently, the correct treatment strategy for these tumors does not depend only on the ability of a single physician, but on a skilled team specialized in this particular tumor. Second line therapies (VeIP, PEI, TIP) can cure 25%–40% of patients, but improved strategies for resistant tumors are desperately needed. High-dose chemotherapy has shown very good results in some studies while being less impressive in others. In any case, it should remain an option for relapsing patients and could be used in some cases of upfront chemotherapy in patients with slow marker decline, but this should only be considered in referring centers.

Salvage Treatment With Paclitaxel, Ifosfamide, and Cisplatin Plus High-Dose Carboplatin, Etoposide, and Thiotepa Followed by Autologous Stem-Cell Rescue in Patients With Relapsed or Refractory Germ Cell Cancer

2001 ◽  
Vol 19 (1) ◽  
pp. 81-88 ◽  
Author(s):  
O. Rick ◽  
C. Bokemeyer ◽  
J. Beyer ◽  
J. T. Hartmann ◽  
N. Schwella ◽  
...  
Keyword(s):  
Stem Cell ◽  
Germ Cell ◽  
Tumor Progression ◽  
Stable Disease ◽  
Multiorgan Failure ◽  
Cell Cancer ◽  
Germ Cell Tumors ◽  
Salvage Treatment ◽  
High Dose ◽  
Salvage Regimen

PURPOSE: To study feasibility and efficacy of a new salvage regimen in patients with relapsed and/or refractory germ cell tumors. PATIENTS AND METHODS: Between May 1995 and February 1997, 80 patients were entered onto a phase II study. Conventional-dose salvage treatment with three cycles of paclitaxel 175 mg/m2, ifosfamide 5 × 1.2 g/m2, and cisplatin 5 × 20 mg/m2 (TIP) was followed by one cycle of high-dose chemotherapy (HDCT) with carboplatin 500 mg/m2 × 3, etoposide 600 mg/m2 × 4, and thiotepa 150 to 250 mg/m2 × 3 (CET). In 23 patients, one additional cycle of paclitaxel 175 mg/m2 and ifosfamide 5 g/m2 (TI) was given immediately before TIP to improve stem-cell mobilization. RESULTS: Fifty-five (69%) of 80 patients responded to TIP, 24 (30%) of 80 patients had stable disease (n = 5) or tumor progression (n = 19), and one patient died. Only 62 (78%) of 80 patients received subsequent HDCT. Among those, 41 (66%) of 62 patients responded and 20 (32%) of 62 patients had stable disease (n = 3) or tumor progression (n = 17). One patient died after HDCT from multiorgan failure. Survival probabilities at 3 years were 30% for overall and 25% for event-free survival. Peripheral neurotoxicity with sensorimotor impairment grade 2 through 4 in 29%, paresthesias grade 2 through 4 in 24%, and skin toxicity grade 2 through 3 in 15% of patients were the most relevant side effects. CONCLUSION: Treatment with TIP followed by high-dose CET is feasible and can induce long-term remissions in 25% of patients with relapsed or refractory germ cell tumors. Peripheral nervous toxicity in approximately one third of patients is a disadvantage of this salvage strategy.

A randomized trial of standard chemotherapy v a high-dose chemotherapy regimen in the treatment of poor prognosis nonseminomatous germ-cell tumors.

1988 ◽  
Vol 6 (6) ◽  
pp. 1031-1040 ◽  
Author(s):  
R F Ozols ◽  
D C Ihde ◽  
W M Linehan ◽  
J Jacob ◽  
Y Ostchega ◽  
...  
Keyword(s):  
Germ Cell ◽  
Dose Regimen ◽  
Standard Therapy ◽  
Poor Prognosis ◽  
Cell Cancer ◽  
Germ Cell Tumors ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
High Dose Regimen ◽  
Disease Free

We performed a prospective randomized trial of a high-dose chemotherapy regimen v standard cisplatin-based chemotherapy in poor prognosis nonseminomatous germ-cell cancer patients. The high-dose regimen consisting of twice the standard dose of cisplatin (P), along with vinblastine (Ve), bleomycin (B), and the epipodophylotoxin etoposide (VP-16) (V) (PVeBV) was compared to the classic regimen with normal dose cisplatin, vinblastine, and bleomycin (PVeB). Eligibility criteria included large abdominal masses, liver metastases, multiple pulmonary metastases, brain metastases, marked elevations in serum tumor markers (alpha-fetoprotein greater than 1,000 ng/mL or the beta-subunit of human chorionic gonadotropin greater than 10,000 mIU), unfavorable histology (pure choriocarcinoma), or extragonadal germ-cell tumors. Fifty-two consecutive patients with poor prognostic features were randomized to receive either PVeBV or PVeB. The median follow-up is 4 years. Treatment with the high-dose regimen increased the complete remission rate (88% v 67%, P = .14) and was associated with a lower relapse rate (17% v 41%, P = .2). The median survival of patients receiving standard therapy was 30 months, while the median survival for patients receiving the high-dose regimen has not been reached. Actuarial 5-year survival for patients treated with the high-dose regimen is 78%, compared with 48% for patients receiving standard therapy (two-sided Mantel-Cox test = .06). Disease-free survival was also superior for patients randomized to PVeBV (P = .03). Sixty-eight percent of patients (23 of 34) randomized to PVeBV are alive and continuously disease-free, compared with 33% (six of 18) for PVeB (P = .02). The major difference in toxicity between the high-dose regimen and standard therapy was the severity of myelosuppression and the incidence of severe hearing loss. Ninety-one percent of patients treated with PVeBV had a WBC count less than 1,000/microL, compared with 50% of patients receiving PVeB (P less than .05). Hearing aids were recommended for 12 patients who received PVeBV and two who received PVeB. The increased effectiveness of the PVeBV regimen in poor prognosis germ-cell cancer patients may relate to the double-dose cisplatin, the addition of VP-16, or to a synergistic effect of these two drugs.

scholarly journals Clinical Characteristics and Treatment Outcomes of Patients With Advanced Germ Cell Tumor Treated at a Tertiary Cancer Center in Brazil

2019 ◽  
pp. 1-8
Author(s):  
Vitor Fiorin Vasconcellos ◽  
Diogo Assed Bastos ◽  
Allan A. Lima Pereira ◽  
Gabriel Yoshiyuki Watarai ◽  
Bruno Rodriguez Pereira ◽  
...  
Keyword(s):  
Germ Cell ◽  
Treatment Outcomes ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Multivariable Analysis ◽  
Germ Cell Tumors ◽  
Cancer Center ◽  
High Dose ◽  
Poor Risk

PURPOSE Reported treatment outcomes for patients with advanced germ cell tumors (aGCT) are based mainly on series from developed nations. Data from low- and middle-income countries are underrepresented. MATERIAL AND METHODS From 2000 to 2015, a retrospective analysis identified 300 patients with aGCT treated at our institution. Kaplan-Meier methods were used for analysis of progression-free survival (PFS) and overall survival (OS) according to the International Germ Cell Consensus Classification Group (IGCCCG). RESULTS Patients’ median age was 28 years. According to the IGCCCG, 57% had good-, 18.3% intermediate-, and 24.7% poor-risk disease. Median α-fetoprotein levels were 2.9, 243, and 3,998 ng/mL, and those of human chorionic gonadotropin were 0.4, 113, and 301.5 mUI/mL in IGCCCG good-, intermediate-, and poor-risk groups, respectively. At a median 46 months of follow-up, 93 PFS events and 45 deaths had occurred and estimated 5-year PFS and OS were 69% and 85%, respectively, including 83% and 95.3% in good-risk, 70.9% and 83.6% in intermediate-risk, and 35.1% and 62.2% in poor-risk patients, respectively. In multivariable analysis, Eastern Cooperative Oncology Group performance status ≥ 2 was a significant independent prognostic factor with a hazard ratio of 2.58 (95% CI, 1.55 to 4.29; P < .001) and 6.20 (95% CI, 2.97 to 12.92; P < .001) for PFS and OS, respectively. CONCLUSION Brazilian patients with aGCT in this cohort had similar outcomes as patients in the IGCCCG database. In comparison with contemporary series, patients with intermediate- and poor-risk aGCT had slightly inferior PFS and OS, possibly due to a high percentage of patients with poor performance status and less use of high-dose chemotherapy.

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