Treatment of refractory germ cell tumors in children with paclitaxel, ifosfamide, and carboplatin: A report from the Children's Oncology Group AGCT0521 study

Pashankar, Farzana; Frazier, Lindsay; Krailo, Mark; Xia, Chengcai; Pappo, Alberto S.; Malogolowkin, Marcio H.; Olson, Thomas A.; Rodríguez‐Galindo, Carlos

doi:10.1002/pbc.27111

Cited by 12 publications

(13 citation statements)

References 21 publications

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“…This cohort also experienced a reassuring safety profile with paclitaxel, as no patients experienced neurotoxicity or paclitaxel-induced anaphylaxis or severe allergic reactions, and other side effects were seen infrequently. The favorable safety profile seen in this pediatric cohort reassuringly was in line with other pediatric case reports that safely used paclitaxel to treat KS in low- [ 16 ], middle- [ 30 ], and high-income [ 31 ] settings, and to treat other pediatric cancers [ 32 , 33 ]. Similarly, in a large randomized controlled trial of adults with HIV associated KS in LMIC, paclitaxel was well tolerated with a favorable safety profile [ 15 ].…”

Section: Discussionsupporting

confidence: 84%

Use of Paclitaxel to Successfully Treat Children, Adolescents, and Young Adults with Kaposi Sarcoma in Southwestern Tanzania

et al. 2021

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Treating Kaposi sarcoma (KS) in children, adolescents, and young adults (AYA) remains a challenge in low- and middle-income countries (LMIC) where chemotherapy options and availability are limited. We describe a retrospective cohort review of pediatric patients with KS treated with paclitaxel in Mbeya, Tanzania, between 1 March 2011 and 31 December 2019. Paclitaxel was given to patients who had KS relapse, a contraindication to bleomycin, vincristine, and doxorubicin (ABV), special circumstances in which a clinician determined that paclitaxel was preferable to ABV, or experienced treatment failure, defined as persistent KS symptoms at the completion of treatment. All patients also received multidisciplinary palliative care. Seventeen patients aged 5.1–21.3 years received paclitaxel, of whom 47.1% (8/17) had treatment failure, 29.4% (5/17) received paclitaxel as initial treatment, and 23.5% (4/17) had relapsed. All HIV positive patients (16/17) were given anti-retroviral therapy (ART) and 87.5% (14/16) achieved viral load <1000 cp/mL. At censure, 82.3% (14/17) of patients were alive—71.4% (10/14) achieved complete clinical remission and 28.6% (4/14) achieved a partial response. The median follow up was 37.3 months (range 8.0–83.5, IQR 19.7–41.6), and no patients were lost to follow up. In this cohort, high rates of long-term survival and favorable outcomes were possible with paclitaxel treatment.

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Section: Discussionsupporting

confidence: 84%

Use of Paclitaxel to Successfully Treat Children, Adolescents, and Young Adults with Kaposi Sarcoma in Southwestern Tanzania

et al. 2021

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“…There is no consensus about this issue in adult series as well. Pashankar et al 11 reported more than 50% of children in PR after two courses of TIP (paclitaxel 135 mg/m 2 /day on day 1, ifosfamide 1800 mg/m 2 on days 1 to 5, and carboplatin with AUC 6.5 on day 1). In our experience, after SLCT based on "ICE," 19 of 21 patients reached PR or CR.…”

Section: F I G U R E 2 Os Of Relapsed and Refractory Patientsmentioning

confidence: 99%

“…Nonetheless, data and experience regarding secondline treatment for relapsed/refractory GCT in the pediatric setting are sparse, especially with regard to long-term outcome. [10][11][12] We present the experience of the Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP) concerning treatment of children with relapsed/refractory malignant GCTs after first-line platinumbased chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Salvage treatment for children with relapsed/refractory germ cell tumors: The Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) experience

Pasquale

D’Angelo²,

Crocoli

et al. 2019

Pediatric Blood & Cancer

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Background: Malignant germ cell tumors (GCTs) are a heterogeneous group of rare neoplasms in children. Optimal outcome is achieved with multimodal therapies for patients with both localized and advanced disease, especially after the introduction of platinum-based chemotherapy regimens. In this respect, data on salvage treatment for children with relapsed or platinum-refractory disease are still limited.Methods: Retrospective analysis of data regarding patients affected by malignant GCTs with platinum-refractory or relapsed disease after first-line treatment according to AIEOP TCGM 2004 protocol was conducted.Results: Twenty-one patients, 15 females and 6 males, were considered for the analysis. All 21 patients received second-line conventional chemotherapy (SLCT), two of these immediately after surgery for local relapse removal. Two patients showed a progression of disease during SLCT and died of disease shortly thereafter, whereas 19 patients were in partial remission (PR) or complete remission (CR) after SLCT. Treatment after SLCT consisted in surgery on residual tumor mass (9/19) followed by high dose of chemotherapy (HDCT) with autologous hematopoietic stem cell support (16/19). The overall survival (OS) and event-free survival of the whole populations are 71% and 66.6%, respectively. Platinum-refractory patients OS is 54.5% compared with 91.5% of the relapsed group. There were no treatment-related deaths. Conclusion:SLCT followed or not by HDCT is an effective salvage treatment for children with relapsed/refractory GCTs. However, the role of HDCT following SLCT needs to be further investigated, especially regarding the identification of specific patient subgroups, which can benefit from this more intensive treatment.

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“…The conditioning in the French cohort was based on etoposide–thiotepa in five cases and carboPEC in four patients [ 15 , 16 ]. The Children’s Oncology Group (COG) group used a paclitaxel, ifosfamide, and carboplatin (TIC) regimen (paclitaxel 135 mg/m 2 /day on day 1, ifosfamide 1800 mg/m 2 /dose on days 1–5, and carboplatin with area under curve (AUC) 6.5 on day 1) as a second-line therapy in children with relapsed GCT and reported that the overall response rate was 44% using combined Response Evaluation Criteria in Solid Tumors (RECIST) response and tumor marker decline [ 17 ]. In this study, ACST was performed in five patients; however, only one of five patients was cured, and no details on the HDCT regimen were provided.…”

Section: Discussionmentioning

confidence: 99%

Melphalan, Etoposide, and Carboplatin Megatherapy with Autologous Stem Cell Transplantation in Children with Relapsing or Therapy-Resistant Extracranial Germ-Cell Tumors—A Retrospective Analysis

Ussowicz

Mielcarek‐Siedziuk

Musiał³

et al. 2020

Cancers

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Pediatric germ cell tumors (GCTs) are a group of chemosensitive malignancies with a 90% curability rate. We report a series of children with relapsing or therapy-resistant GCT treated with melphalan–etoposide–carboplatin high-dose chemotherapy (HDCT) and autologous stem cell transplantation. This consisted of 18 children, either with GCTs after relapse (nine patients) or with an unsatisfactory response to first-line chemotherapy (nine patients), who underwent HDCT. The HDCT regimens MEC1 (carboplatin 1500 mg/m2, etoposide 1800 mg/m2, and melphalan 140 mg/m2) and MEC2 (carboplatin 800 mg/m2, etoposide 800 mg/m2, and melphalan 140 mg/m2) were each used in nine patients. The median observation time was 81 months, the 5-year overall survival (OS) was 76%, and the event-free survival (EFS) was 70.8%. Non-relapse mortality was 0%, and four patients died after HDCT due to progression of the malignancy. No difference in OS or EFS was noted between the MEC1 and MEC2 protocols. The 5-year OS and 5-year EFS were higher in children treated with autologous stem cell transplantation before the age of four years. The presence of metastatic disease or time of HDCT consolidation during first/subsequent line chemotherapy did not affect patient survival. The melphalan–etoposide–carboplatin protocol is feasible in pediatric GCT, but is associated with potentially life-threatening complications. In conclusion, the use of HDCT must be examined in well-designed clinical trials, and the identification of patients who can benefit from this approach is critical to avoid overtreatment.

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Treatment of refractory germ cell tumors in children with paclitaxel, ifosfamide, and carboplatin: A report from the Children's Oncology Group AGCT0521 study

Abstract: TIC is active in relapsed pediatric MGCT and should be considered for salvage therapy in children. In adolescents and older adults with relapse MGCT, TIP or high-dose chemotherapy with stem cell remain the standard therapy.

Cited by 12 publications

References 21 publications

Use of Paclitaxel to Successfully Treat Children, Adolescents, and Young Adults with Kaposi Sarcoma in Southwestern Tanzania

Use of Paclitaxel to Successfully Treat Children, Adolescents, and Young Adults with Kaposi Sarcoma in Southwestern Tanzania

Salvage treatment for children with relapsed/refractory germ cell tumors: The Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) experience

Melphalan, Etoposide, and Carboplatin Megatherapy with Autologous Stem Cell Transplantation in Children with Relapsing or Therapy-Resistant Extracranial Germ-Cell Tumors—A Retrospective Analysis

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