Infusional gemcitabine + docetaxel/melphalan/carboplatin (GemDMC) ± bevacizumab (BEV) as an effective high-dose chemotherapy (HDC) regimen for refractory of poor-risk relapsed germ-cell tumors (GCT).

Authors

null

Yago Nieto

The University of Texas MD Anderson Cancer Center, Houston, TX

Yago Nieto , Shi-Ming Tu , Matthew T. Campbell , Roland Bassett , Nizar M. Tannir , John Francis Ward , Wayne Lewis Hofstetter , Roy B. Jones , Borje Andersson , Alison M Gulbis , Celina Ledesma , Melissa Timmons , Michelle Trapp , Richard E. Champlin , Lance C. Pagliaro

Organizations

The University of Texas MD Anderson Cancer Center, Houston, TX, Mayo Clinic, Rochester, MN

Research Funding

Other

Background: Tandem HDC with carbo/etoposide (CE) is curative for a portion of relapsed GCT pts. However, outcomes of refractory or high-risk relapsed pts remain poor. We tested a new HDC regimen of GemDMC, based on DNA damage repair inhibition. We combined BEV with HDC given their potential synergy and the high vascularity of GCT metastases. Methods: Eligibility: Intermediate (int)/high-risk (Beyer Model), creatinine ≤1.8 mg/dL and adequate organ function. HDC included BEV (5 mg/kg) preceding GemDMC (HDC #1) and ifosfamide/CE (ICE) (HDC #2). Following accrual of 42 pts, we amended the trial omitting BEV. The trial was powered to distinguish a target 50% 2-yr RFS from an expected 25% in this population. Results: We enrolled 69 male pts in cohorts 1 (BEV, N=42) and 2 (no BEV, N=27) (Table). Pts were heavily pretreated and most had refractory tumors. Main AE: mucositis and renal (4 HDC-related deaths in cohort 1, 1 in cohort 2). Tumor markers normalized in 90% pts with active tumors at HDC. After HDC, 19 pts were in CR and 28 in PRm- (of these, 22 had residual lesions resected with no viable tumor found in 20/22, 2 xRT, 4 monitored). Median f/u = 39 (2-105) mo. The 2-yr RFS rates in cohorts 1 and 2 = 52% and 78%, respectively. Their respective 2-yr OS rates = 55% and 81%. Conclusions: Sequential HDC with GemDMC–ICE shows encouraging outcomes in heavily pretreated and refractory GCT, exceeding the anticipated results. Addition of BEV increases toxicity but not tumor control. Clinical trial information: NCT00936936

BEV (N=42)No BEV (N=27)P
Median age (range)30 (20 - 49)28 (19-56).9
1◦ testis / mediast / retroperit (%)76 / 14 / 1085 / 11 / 4.7
Median # prior regimens4 (2 - 9)4 (2-8).7
Tumor markers at rel/PD: median (range)
AFP (N=29)395 (25–377,426)1,942 (17-750,303).4
B-HCG (N=34)344 (26–89,000)1,482 (22-24,579).5
Prior progression-free interval (%)
≤3 mo9089.9
>3 mo1011
# prior rel/PD (%)
12437.2
21830
3-65833
Cisplatin sensitive (%):
Absol refr3929.2
Refr4539
Sensit1632
% prior surgery of mets6067.6
% prior xRT2130.6
Resp at HDC #1 (%):
No resp (PD / SD)58 (53 / 5)32 (26 / 6).02
PRm+1855
PRm-1310
CR113
Risk (%):
Beyer: Int / high48 / 5262 / 38.3
IPS: Int / high / very high5 / 14 / 817 / 22 / 70.9

Disclaimer

This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org

Abstract Details

Meeting

2017 ASCO Annual Meeting

Session Type

Poster Discussion Session

Session Title

Genitourinary (Nonprostate) Cancer

Track

Genitourinary Cancer—Kidney and Bladder

Sub Track

Germ Cell/Testicular

Clinical Trial Registration Number

NCT00936936

Citation

J Clin Oncol 35, 2017 (suppl; abstr 4519)

DOI

10.1200/JCO.2017.35.15_suppl.4519

Abstract #

4519

Poster Bd #

197

Abstract Disclosures

Similar Abstracts

First Author: Yago Nieto

First Author: Jennifer King