Reduced and compressed cisplatin-based chemotherapy in children and adolescents with intermediate-risk extracranial malignant germ cell tumors

A report from the children's oncology group

Furqan Shaikh, John W. Cullen, Thomas A. Olson, Farzana Pashankar, Marcio H. Malogolowkin, James F. Amatruda, Doojduen Villaluna, Mark Krailo, Deborah F. Billmire, Frederick Rescorla, Rachel A. Egler, Bryan J. Dicken, Jonathan H. Ross, Marc Schlatter, Carlos Rodriguez-Galindo, A. Lindsay Frazier

Research output: Contribution to journalArticle

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Abstract

Purpose To investigate whether event-free survival (EFS) can be maintained among children and adolescents with intermediate-risk (IR) malignant germ cell tumors (MGCT) if the administration of cisplatin, etoposide, and bleomycin (PEb) is reduced from four to three cycles and compressed from 5 to 3 days per cycle. Patients and Methods In a phase 3, single-arm trial, patients with IR MGCT (stage II-IV testicular, II-III ovarian, I-II extragonadal, or stage I gonadal tumors with subsequent recurrence) received three cycles of PEb. A parametric comparator model specified that the observed EFS rate should not be significantly < 92%. As recommended for trials that test a reduction of therapy, a one-sided P value ≤ .10 was used to indicate statistical significance. In a post hoc analysis, we also compared results to the EFS rate of comparable patients treated with four cycles of PEb in two prior studies. Results Among 210 eligible patients enrolled from 2003 to 2011, 4-year EFS (EFS4) rate was 89% (95% confidence interval, 83% to 92%), which was significantly lower than the 92% threshold of the comparison model (P = .08). Among 181 newly diagnosed patients, the EFS4 rate was 87%, compared with 92% for 92 comparable children in the historical cohort (P = .15). The EFS4 rate was significantly associated with stage (stage I, 100%; stage II, 92%; stage III, 85%; and stage IV, 54%; P < .001). Conclusion The EFS rate for children with IR MGCT observed after three cycles of PEb was less than that of a prespecified parametric model, particularly for patients with higher-stage tumors. These data do not support a reduction in the number of cycles of PEb from four to three. However, further investigation of a reduction in the number of cycles for patients with lower-stage tumors is warranted.

Original languageEnglish (US)
Pages (from-to)1203-1210
Number of pages8
JournalJournal of Clinical Oncology
Volume35
Issue number11
DOIs
StatePublished - Apr 10 2017

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Germ Cell and Embryonal Neoplasms
Cisplatin
Disease-Free Survival
Drug Therapy
Survival Rate
Neoplasms
Bleomycin
Etoposide
Confidence Intervals
Recurrence

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Reduced and compressed cisplatin-based chemotherapy in children and adolescents with intermediate-risk extracranial malignant germ cell tumors : A report from the children's oncology group. / Shaikh, Furqan; Cullen, John W.; Olson, Thomas A.; Pashankar, Farzana; Malogolowkin, Marcio H.; Amatruda, James F.; Villaluna, Doojduen; Krailo, Mark; Billmire, Deborah F.; Rescorla, Frederick; Egler, Rachel A.; Dicken, Bryan J.; Ross, Jonathan H.; Schlatter, Marc; Rodriguez-Galindo, Carlos; Frazier, A. Lindsay.

In: Journal of Clinical Oncology, Vol. 35, No. 11, 10.04.2017, p. 1203-1210.

Research output: Contribution to journalArticle

Shaikh, F, Cullen, JW, Olson, TA, Pashankar, F, Malogolowkin, MH, Amatruda, JF, Villaluna, D, Krailo, M, Billmire, DF, Rescorla, F, Egler, RA, Dicken, BJ, Ross, JH, Schlatter, M, Rodriguez-Galindo, C & Frazier, AL 2017, 'Reduced and compressed cisplatin-based chemotherapy in children and adolescents with intermediate-risk extracranial malignant germ cell tumors: A report from the children's oncology group', Journal of Clinical Oncology, vol. 35, no. 11, pp. 1203-1210. https://doi.org/10.1200/JCO.2016.67.6544
Shaikh, Furqan ; Cullen, John W. ; Olson, Thomas A. ; Pashankar, Farzana ; Malogolowkin, Marcio H. ; Amatruda, James F. ; Villaluna, Doojduen ; Krailo, Mark ; Billmire, Deborah F. ; Rescorla, Frederick ; Egler, Rachel A. ; Dicken, Bryan J. ; Ross, Jonathan H. ; Schlatter, Marc ; Rodriguez-Galindo, Carlos ; Frazier, A. Lindsay. / Reduced and compressed cisplatin-based chemotherapy in children and adolescents with intermediate-risk extracranial malignant germ cell tumors : A report from the children's oncology group. In: Journal of Clinical Oncology. 2017 ; Vol. 35, No. 11. pp. 1203-1210.
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title = "Reduced and compressed cisplatin-based chemotherapy in children and adolescents with intermediate-risk extracranial malignant germ cell tumors: A report from the children's oncology group",
abstract = "Purpose To investigate whether event-free survival (EFS) can be maintained among children and adolescents with intermediate-risk (IR) malignant germ cell tumors (MGCT) if the administration of cisplatin, etoposide, and bleomycin (PEb) is reduced from four to three cycles and compressed from 5 to 3 days per cycle. Patients and Methods In a phase 3, single-arm trial, patients with IR MGCT (stage II-IV testicular, II-III ovarian, I-II extragonadal, or stage I gonadal tumors with subsequent recurrence) received three cycles of PEb. A parametric comparator model specified that the observed EFS rate should not be significantly < 92{\%}. As recommended for trials that test a reduction of therapy, a one-sided P value ≤ .10 was used to indicate statistical significance. In a post hoc analysis, we also compared results to the EFS rate of comparable patients treated with four cycles of PEb in two prior studies. Results Among 210 eligible patients enrolled from 2003 to 2011, 4-year EFS (EFS4) rate was 89{\%} (95{\%} confidence interval, 83{\%} to 92{\%}), which was significantly lower than the 92{\%} threshold of the comparison model (P = .08). Among 181 newly diagnosed patients, the EFS4 rate was 87{\%}, compared with 92{\%} for 92 comparable children in the historical cohort (P = .15). The EFS4 rate was significantly associated with stage (stage I, 100{\%}; stage II, 92{\%}; stage III, 85{\%}; and stage IV, 54{\%}; P < .001). Conclusion The EFS rate for children with IR MGCT observed after three cycles of PEb was less than that of a prespecified parametric model, particularly for patients with higher-stage tumors. These data do not support a reduction in the number of cycles of PEb from four to three. However, further investigation of a reduction in the number of cycles for patients with lower-stage tumors is warranted.",
author = "Furqan Shaikh and Cullen, {John W.} and Olson, {Thomas A.} and Farzana Pashankar and Malogolowkin, {Marcio H.} and Amatruda, {James F.} and Doojduen Villaluna and Mark Krailo and Billmire, {Deborah F.} and Frederick Rescorla and Egler, {Rachel A.} and Dicken, {Bryan J.} and Ross, {Jonathan H.} and Marc Schlatter and Carlos Rodriguez-Galindo and Frazier, {A. Lindsay}",
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T1 - Reduced and compressed cisplatin-based chemotherapy in children and adolescents with intermediate-risk extracranial malignant germ cell tumors

T2 - A report from the children's oncology group

AU - Shaikh, Furqan

AU - Cullen, John W.

AU - Olson, Thomas A.

AU - Pashankar, Farzana

AU - Malogolowkin, Marcio H.

AU - Amatruda, James F.

AU - Villaluna, Doojduen

AU - Krailo, Mark

AU - Billmire, Deborah F.

AU - Rescorla, Frederick

AU - Egler, Rachel A.

AU - Dicken, Bryan J.

AU - Ross, Jonathan H.

AU - Schlatter, Marc

AU - Rodriguez-Galindo, Carlos

AU - Frazier, A. Lindsay

PY - 2017/4/10

Y1 - 2017/4/10

N2 - Purpose To investigate whether event-free survival (EFS) can be maintained among children and adolescents with intermediate-risk (IR) malignant germ cell tumors (MGCT) if the administration of cisplatin, etoposide, and bleomycin (PEb) is reduced from four to three cycles and compressed from 5 to 3 days per cycle. Patients and Methods In a phase 3, single-arm trial, patients with IR MGCT (stage II-IV testicular, II-III ovarian, I-II extragonadal, or stage I gonadal tumors with subsequent recurrence) received three cycles of PEb. A parametric comparator model specified that the observed EFS rate should not be significantly < 92%. As recommended for trials that test a reduction of therapy, a one-sided P value ≤ .10 was used to indicate statistical significance. In a post hoc analysis, we also compared results to the EFS rate of comparable patients treated with four cycles of PEb in two prior studies. Results Among 210 eligible patients enrolled from 2003 to 2011, 4-year EFS (EFS4) rate was 89% (95% confidence interval, 83% to 92%), which was significantly lower than the 92% threshold of the comparison model (P = .08). Among 181 newly diagnosed patients, the EFS4 rate was 87%, compared with 92% for 92 comparable children in the historical cohort (P = .15). The EFS4 rate was significantly associated with stage (stage I, 100%; stage II, 92%; stage III, 85%; and stage IV, 54%; P < .001). Conclusion The EFS rate for children with IR MGCT observed after three cycles of PEb was less than that of a prespecified parametric model, particularly for patients with higher-stage tumors. These data do not support a reduction in the number of cycles of PEb from four to three. However, further investigation of a reduction in the number of cycles for patients with lower-stage tumors is warranted.

AB - Purpose To investigate whether event-free survival (EFS) can be maintained among children and adolescents with intermediate-risk (IR) malignant germ cell tumors (MGCT) if the administration of cisplatin, etoposide, and bleomycin (PEb) is reduced from four to three cycles and compressed from 5 to 3 days per cycle. Patients and Methods In a phase 3, single-arm trial, patients with IR MGCT (stage II-IV testicular, II-III ovarian, I-II extragonadal, or stage I gonadal tumors with subsequent recurrence) received three cycles of PEb. A parametric comparator model specified that the observed EFS rate should not be significantly < 92%. As recommended for trials that test a reduction of therapy, a one-sided P value ≤ .10 was used to indicate statistical significance. In a post hoc analysis, we also compared results to the EFS rate of comparable patients treated with four cycles of PEb in two prior studies. Results Among 210 eligible patients enrolled from 2003 to 2011, 4-year EFS (EFS4) rate was 89% (95% confidence interval, 83% to 92%), which was significantly lower than the 92% threshold of the comparison model (P = .08). Among 181 newly diagnosed patients, the EFS4 rate was 87%, compared with 92% for 92 comparable children in the historical cohort (P = .15). The EFS4 rate was significantly associated with stage (stage I, 100%; stage II, 92%; stage III, 85%; and stage IV, 54%; P < .001). Conclusion The EFS rate for children with IR MGCT observed after three cycles of PEb was less than that of a prespecified parametric model, particularly for patients with higher-stage tumors. These data do not support a reduction in the number of cycles of PEb from four to three. However, further investigation of a reduction in the number of cycles for patients with lower-stage tumors is warranted.

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