High-Dose Chemotherapy and Autologous Peripheral-Blood Stem-Cell Transplantation for Relapsed Metastatic Germ Cell Tumors: The Indiana University Experience

Abstract

Patients with relapsed metastatic germ cell tumor (GCT) can be cured with second-line and even third-line regimens. We report survival outcomes of patients treated with high-dose chemotherapy (HDCT) and peripheral-blood stem-cell transplantation (PBSCT) at Indiana University between 2004 and 2014. Patients and MethodsWe conducted a retrospective analysis of 364 consecutive patients with GCT who progressed after cisplatin-based combination chemotherapy and were subsequently treated with HDCT and PBSCT. Three hundred forty-one patients received two consecutive courses of HDCT consisting of 700 mg/m 2 carboplatin and 750 mg/m 2 etoposide, each for 3 consecutive days, and each followed by PBSCT. Twenty-three patients received only a single course of HDCT because of progressive disease or toxicity. Cox proportional hazards models were used to test predictors of disease progression. ResultsThe median age was 32 years (range, 17 to 70 years). With a median follow-up of 3.3 years, the 2-year progression-free survival (PFS) was 60% (95% CI, 55% to 65%) and the 2-year overall survival was 66% (95% CI, 60% to 70%). Three hundred three patients received HDCT as second-line therapy with a 2-year PFS of 63% (95% CI, 57% to 68%), and 61 patients received HDCT as third-line or later therapy with a 2-year PFS of 49% (95% CI, 36% to 61%). In a multivariable analysis, factors associated with disease progression included use of HDCT as third-line or later therapy, platinumrefractory disease, mediastinal primary tumor site, nonseminoma histology, intermediate-or poorrisk disease at the time of GCT diagnosis, and human chorionic gonadotropin $ 1,000 mIU/mL at initiation of HDCT. There were nine treatment-related deaths. Secondary leukemia developed in five patients. ConclusionThis large single-institution study demonstrates that patients with relapsed metastatic GCT are curable by HDCT plus PBSCT even when used in third-line or later therapy.

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

“…In adults, the management of relapsed GCT is either with standard‐dose chemotherapy or high‐dose chemotherapy with autologous stem cell rescue . There are no completed randomized trials comparing these two approaches and currently no consensus exists on whether initial salvage should be standard‐dose or high‐dose chemotherapy.…”

“…In a multivariate analysis of 519 patients, treatment regimen (PEB vs. JEB) did not show a significant difference in outcome . In addition, high‐dose carboplatin is also an integral part of high‐dose chemotherapy regimens used for relapse GCT in adults . This provided the rationale for substituting carboplatin for cisplatin in the TIC regimen.…”

High‐dose chemotherapy plus peripheral blood stem cell transplantation for patients with relapsed germ cell tumors and active brain metastases

“…A second patient died of septic shock and multiorgan failure during the first cycle of HDCT. Toxicity otherwise was as previously published with this regimen by our institution . There was no clinical evidence of CNS bleeds during HDCT.…”

The Role of Salvage High-Dose Chemotherapy in Relapsed Male Germ Cell Tumors

“…Several additional retrospective series including one with patients having bone metastases and a retrospective analysis of the German Testicular Cancer Study Group reporting on 143 patients undergoing either conventional-dose (n = 48) or high-dose (n = 95) therapy as first salvage could also confirm the superiority of HD-CT over conventional-dose therapy [16,17]. Recently, the group from Indiana University published long-term disease-free survival rates with HD-CT of 25, 33, and 40% of patients with either mediastinal primary, absolute platinum-refractory disease, or progressive brain metastases as poor-risk features [18]. Moreover, patients with unresectable late relapse after first- or further-line treatment showed very dismal outcomes with only 15% of patients achieving long-term PFS even after salvage HD-CT [19].…”