Bevacizumab/high-dose chemotherapy with autologous stem-cell transplant for poor-risk relapsed or refractory germ-cell tumors

Yago Nieto, S. M. Tu, R. Bassett, R. B. Jones, A. M. Gulbis, N. Tannir, A. Kingham, C. Ledesma, K. Margolin, L. Holmberg, R. Champlin, L. Pagliaro

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: High-dose chemotherapy (HDC) using sequential cycles of carboplatin/etoposide is curative for relapsed germ-cell tumors (GCT). However, outcomes of high-risk patients in advanced relapse remain poor. We previously developed a new HDC regimen combining infusional gemcitabine with docetaxel/melphalan/carboplatin (GemDMC), with preliminary high activity in refractory GCT. Given the high vascular endothelial growth factor expression in metastatic GCT and the synergy between bevacizumab and chemotherapy, we studied concurrent bevacizumab and sequential HDC using GemDMC and ifosfamide/carboplatin/etoposide (ICE) in patients with poor-risk relapsed or refractory disease. Patients and methods: Eligibility criteria included intermediate/high-risk relapse (Beyer Model), serum creatinine ≤ 1.8 mg/dl and adequate pulmonary/cardiac/hepatic function. Patients received sequential HDC cycles with bevacizumab preceding GemDMC (cycle 1) and ICE (cycle 2). The trial was powered to distinguish a target 50% 2-year relapse-free survival (RFS) from an expected 25% 2-year RFS in this population. Results: We enrolled 43 male patients, median age 30 (20-49) years, with absolute refractory (N = 20), refractory (N = 17) or cisplatin-sensitive (N = 6) disease, after a median 3 (1-5) prior relapses. Disease status right before HDC was unresponsive (N = 24, progressive disease 22, stable disease 2), partial response with positive markers (PRm+) (N = 8), PRm- (N = 7) or complete response (N = 4). Main toxicities were mucositis and renal. Four patients (three with baseline marginal renal function) died from HDC-related complications. Tumor markers normalized in 85% patients. Resection of residual lesions (N = 13) showed necrosis (N = 4), mature teratoma (N = 2), necrosis/teratoma (N = 3) and viable tumor (N = 4). At median follow-up of 46 (9-84) months, the RFS and overall survival rates are 55.8% and 58.1%, respectively. Conclusions: Sequential bevacizumab/GemDMC-bevacizumab/ICE shows encouraging outcomes in heavily pretreated and refractory GCT, exceeding the results expected in this difficult to treat population.

Original languageEnglish (US)
Article numbermdv310
Pages (from-to)2125-2132
Number of pages8
JournalAnnals of Oncology
Volume26
Issue number10
DOIs
StatePublished - Oct 1 2015
Externally publishedYes

Fingerprint

Germ Cell and Embryonal Neoplasms
Carboplatin
docetaxel
gemcitabine
Stem Cells
Transplants
Drug Therapy
Melphalan
Etoposide
Recurrence
Ifosfamide
Teratoma
Survival
Necrosis
Kidney
Mucositis
Bevacizumab
Tumor Biomarkers
Vascular Endothelial Growth Factor A
Cisplatin

Keywords

  • Autologous transplantation
  • Bevacizumab
  • Docetaxel
  • Gemcitabine
  • Germ-cell tumors
  • High-dose chemotherapy

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Nieto, Y., Tu, S. M., Bassett, R., Jones, R. B., Gulbis, A. M., Tannir, N., ... Pagliaro, L. (2015). Bevacizumab/high-dose chemotherapy with autologous stem-cell transplant for poor-risk relapsed or refractory germ-cell tumors. Annals of Oncology, 26(10), 2125-2132. [mdv310]. https://doi.org/10.1093/annonc/mdv310

Bevacizumab/high-dose chemotherapy with autologous stem-cell transplant for poor-risk relapsed or refractory germ-cell tumors. / Nieto, Yago; Tu, S. M.; Bassett, R.; Jones, R. B.; Gulbis, A. M.; Tannir, N.; Kingham, A.; Ledesma, C.; Margolin, K.; Holmberg, L.; Champlin, R.; Pagliaro, L.

In: Annals of Oncology, Vol. 26, No. 10, mdv310, 01.10.2015, p. 2125-2132.

Research output: Contribution to journalArticle

Nieto, Y, Tu, SM, Bassett, R, Jones, RB, Gulbis, AM, Tannir, N, Kingham, A, Ledesma, C, Margolin, K, Holmberg, L, Champlin, R & Pagliaro, L 2015, 'Bevacizumab/high-dose chemotherapy with autologous stem-cell transplant for poor-risk relapsed or refractory germ-cell tumors', Annals of Oncology, vol. 26, no. 10, mdv310, pp. 2125-2132. https://doi.org/10.1093/annonc/mdv310
Nieto, Yago ; Tu, S. M. ; Bassett, R. ; Jones, R. B. ; Gulbis, A. M. ; Tannir, N. ; Kingham, A. ; Ledesma, C. ; Margolin, K. ; Holmberg, L. ; Champlin, R. ; Pagliaro, L. / Bevacizumab/high-dose chemotherapy with autologous stem-cell transplant for poor-risk relapsed or refractory germ-cell tumors. In: Annals of Oncology. 2015 ; Vol. 26, No. 10. pp. 2125-2132.
@article{3603930edc2343abb334da3a68b17064,
title = "Bevacizumab/high-dose chemotherapy with autologous stem-cell transplant for poor-risk relapsed or refractory germ-cell tumors",
abstract = "Background: High-dose chemotherapy (HDC) using sequential cycles of carboplatin/etoposide is curative for relapsed germ-cell tumors (GCT). However, outcomes of high-risk patients in advanced relapse remain poor. We previously developed a new HDC regimen combining infusional gemcitabine with docetaxel/melphalan/carboplatin (GemDMC), with preliminary high activity in refractory GCT. Given the high vascular endothelial growth factor expression in metastatic GCT and the synergy between bevacizumab and chemotherapy, we studied concurrent bevacizumab and sequential HDC using GemDMC and ifosfamide/carboplatin/etoposide (ICE) in patients with poor-risk relapsed or refractory disease. Patients and methods: Eligibility criteria included intermediate/high-risk relapse (Beyer Model), serum creatinine ≤ 1.8 mg/dl and adequate pulmonary/cardiac/hepatic function. Patients received sequential HDC cycles with bevacizumab preceding GemDMC (cycle 1) and ICE (cycle 2). The trial was powered to distinguish a target 50{\%} 2-year relapse-free survival (RFS) from an expected 25{\%} 2-year RFS in this population. Results: We enrolled 43 male patients, median age 30 (20-49) years, with absolute refractory (N = 20), refractory (N = 17) or cisplatin-sensitive (N = 6) disease, after a median 3 (1-5) prior relapses. Disease status right before HDC was unresponsive (N = 24, progressive disease 22, stable disease 2), partial response with positive markers (PRm+) (N = 8), PRm- (N = 7) or complete response (N = 4). Main toxicities were mucositis and renal. Four patients (three with baseline marginal renal function) died from HDC-related complications. Tumor markers normalized in 85{\%} patients. Resection of residual lesions (N = 13) showed necrosis (N = 4), mature teratoma (N = 2), necrosis/teratoma (N = 3) and viable tumor (N = 4). At median follow-up of 46 (9-84) months, the RFS and overall survival rates are 55.8{\%} and 58.1{\%}, respectively. Conclusions: Sequential bevacizumab/GemDMC-bevacizumab/ICE shows encouraging outcomes in heavily pretreated and refractory GCT, exceeding the results expected in this difficult to treat population.",
keywords = "Autologous transplantation, Bevacizumab, Docetaxel, Gemcitabine, Germ-cell tumors, High-dose chemotherapy",
author = "Yago Nieto and Tu, {S. M.} and R. Bassett and Jones, {R. B.} and Gulbis, {A. M.} and N. Tannir and A. Kingham and C. Ledesma and K. Margolin and L. Holmberg and R. Champlin and L. Pagliaro",
year = "2015",
month = "10",
day = "1",
doi = "10.1093/annonc/mdv310",
language = "English (US)",
volume = "26",
pages = "2125--2132",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
number = "10",

}

TY - JOUR

T1 - Bevacizumab/high-dose chemotherapy with autologous stem-cell transplant for poor-risk relapsed or refractory germ-cell tumors

AU - Nieto, Yago

AU - Tu, S. M.

AU - Bassett, R.

AU - Jones, R. B.

AU - Gulbis, A. M.

AU - Tannir, N.

AU - Kingham, A.

AU - Ledesma, C.

AU - Margolin, K.

AU - Holmberg, L.

AU - Champlin, R.

AU - Pagliaro, L.

PY - 2015/10/1

Y1 - 2015/10/1

N2 - Background: High-dose chemotherapy (HDC) using sequential cycles of carboplatin/etoposide is curative for relapsed germ-cell tumors (GCT). However, outcomes of high-risk patients in advanced relapse remain poor. We previously developed a new HDC regimen combining infusional gemcitabine with docetaxel/melphalan/carboplatin (GemDMC), with preliminary high activity in refractory GCT. Given the high vascular endothelial growth factor expression in metastatic GCT and the synergy between bevacizumab and chemotherapy, we studied concurrent bevacizumab and sequential HDC using GemDMC and ifosfamide/carboplatin/etoposide (ICE) in patients with poor-risk relapsed or refractory disease. Patients and methods: Eligibility criteria included intermediate/high-risk relapse (Beyer Model), serum creatinine ≤ 1.8 mg/dl and adequate pulmonary/cardiac/hepatic function. Patients received sequential HDC cycles with bevacizumab preceding GemDMC (cycle 1) and ICE (cycle 2). The trial was powered to distinguish a target 50% 2-year relapse-free survival (RFS) from an expected 25% 2-year RFS in this population. Results: We enrolled 43 male patients, median age 30 (20-49) years, with absolute refractory (N = 20), refractory (N = 17) or cisplatin-sensitive (N = 6) disease, after a median 3 (1-5) prior relapses. Disease status right before HDC was unresponsive (N = 24, progressive disease 22, stable disease 2), partial response with positive markers (PRm+) (N = 8), PRm- (N = 7) or complete response (N = 4). Main toxicities were mucositis and renal. Four patients (three with baseline marginal renal function) died from HDC-related complications. Tumor markers normalized in 85% patients. Resection of residual lesions (N = 13) showed necrosis (N = 4), mature teratoma (N = 2), necrosis/teratoma (N = 3) and viable tumor (N = 4). At median follow-up of 46 (9-84) months, the RFS and overall survival rates are 55.8% and 58.1%, respectively. Conclusions: Sequential bevacizumab/GemDMC-bevacizumab/ICE shows encouraging outcomes in heavily pretreated and refractory GCT, exceeding the results expected in this difficult to treat population.

AB - Background: High-dose chemotherapy (HDC) using sequential cycles of carboplatin/etoposide is curative for relapsed germ-cell tumors (GCT). However, outcomes of high-risk patients in advanced relapse remain poor. We previously developed a new HDC regimen combining infusional gemcitabine with docetaxel/melphalan/carboplatin (GemDMC), with preliminary high activity in refractory GCT. Given the high vascular endothelial growth factor expression in metastatic GCT and the synergy between bevacizumab and chemotherapy, we studied concurrent bevacizumab and sequential HDC using GemDMC and ifosfamide/carboplatin/etoposide (ICE) in patients with poor-risk relapsed or refractory disease. Patients and methods: Eligibility criteria included intermediate/high-risk relapse (Beyer Model), serum creatinine ≤ 1.8 mg/dl and adequate pulmonary/cardiac/hepatic function. Patients received sequential HDC cycles with bevacizumab preceding GemDMC (cycle 1) and ICE (cycle 2). The trial was powered to distinguish a target 50% 2-year relapse-free survival (RFS) from an expected 25% 2-year RFS in this population. Results: We enrolled 43 male patients, median age 30 (20-49) years, with absolute refractory (N = 20), refractory (N = 17) or cisplatin-sensitive (N = 6) disease, after a median 3 (1-5) prior relapses. Disease status right before HDC was unresponsive (N = 24, progressive disease 22, stable disease 2), partial response with positive markers (PRm+) (N = 8), PRm- (N = 7) or complete response (N = 4). Main toxicities were mucositis and renal. Four patients (three with baseline marginal renal function) died from HDC-related complications. Tumor markers normalized in 85% patients. Resection of residual lesions (N = 13) showed necrosis (N = 4), mature teratoma (N = 2), necrosis/teratoma (N = 3) and viable tumor (N = 4). At median follow-up of 46 (9-84) months, the RFS and overall survival rates are 55.8% and 58.1%, respectively. Conclusions: Sequential bevacizumab/GemDMC-bevacizumab/ICE shows encouraging outcomes in heavily pretreated and refractory GCT, exceeding the results expected in this difficult to treat population.

KW - Autologous transplantation

KW - Bevacizumab

KW - Docetaxel

KW - Gemcitabine

KW - Germ-cell tumors

KW - High-dose chemotherapy

UR - http://www.scopus.com/inward/record.url?scp=84943744918&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84943744918&partnerID=8YFLogxK

U2 - 10.1093/annonc/mdv310

DO - 10.1093/annonc/mdv310

M3 - Article

C2 - 26199392

AN - SCOPUS:84943744918

VL - 26

SP - 2125

EP - 2132

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 10

M1 - mdv310

ER -