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Survival outcomes of patients with germ cell tumors treated with high-dose chemotherapy for refractory or relapsing disease.

ABSTRACT: Male patients with metastatic germ cell tumors can be cured in up to 96% of cases depending on stage and IGCCCG prognosis group. Treatment in relapse consists of conventional or high-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) combined with local treatment modalities.Most patients were classified as poor risk according to IGCCCG (n = 24; 52%) and as intermediate (n = 12), high (n = 16), or very high risk (n = 9) at time of first relapse according to IPFSG criteria. In 67% of patients (n = 31) HDCT/ASCT was performed as first salvage treatment in relapse or for primary refractory disease following first line chemotherapy. In 46% of patients (n = 21) progressive disease was documented after mobilization and prior to HDCT/ASCT. Median progression free survival (mPFS) was 7.4 months (95% confidence interval (CI): 1.3-13.6) while median overall survival (mOS) was 22.2 months (95% CI: 8.9-35.5). When stratified for IPFSG risk group, mPFS (p < 0.001) and mOS (p = 0.009) differed significantly between risk groups (very low vs. low vs. intermediate vs. high vs. very high). Metastases to liver/bone/brain and platinum refractory disease were independent risk factors for inferior PFS (p = 0.024; p = 0.008) but not OS.Forty-six patients treated with HDCT/ASCT at the university clinics in Heidelberg and Nuremberg between 2000-2016 were identified and analyzed. Data was collected retrospectively.HDCT/ASCT offers a potential curative strategy for patients with relapsed GCT. Improvement is still needed in patients with intermediate, high, and very high IPFSG risk group.

SUBMITTER: Zschabitz S

PROVIDER: S-EPMC5976483 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Survival outcomes of patients with germ cell tumors treated with high-dose chemotherapy for refractory or relapsing disease.

Zschäbitz Stefanie S Distler Florian A FA Krieger Benjamin B Wuchter Patrick P Schäfer-Eckart Kerstin K Jenzer Maximilian M Hohenfellner Markus M Dreger Peter P Haag Georg Martin GM Jäger Dirk D Pahernik Sascha S Grüllich Carsten C

Oncotarget 20180427 32

<h4>Introduction</h4>Male patients with metastatic germ cell tumors can be cured in up to 96% of cases depending on stage and IGCCCG prognosis group. Treatment in relapse consists of conventional or high-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) combined with local treatment modalities.<h4>Results</h4>Most patients were classified as poor risk according to IGCCCG (<i>n</i> = 24; 52%) and as intermediate (<i>n</i> = 12), high (<i>n</i> = 16), or very high risk (<i> ...[more]

PMID: 29854297

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Project description: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. CLINICALTRIALSGOV:NCT00936936.

Project description:Despite having a higher mortality risk than conventional chemotherapeutics, high-dose chemotherapy (HDCT) has the potential to be curative in relapsed/refractory germ-cell tumors. Therefore, selecting the best patient group for this treatment is critical. This study aimed to determine the factors that affect survival in our relapsed/refractory GCT cohort who received HDCT and autologous stem-cell transplantation. Between September 2010 and 2020, we included in the study 44 relapsed/refractory male patients with GCT treated with HDCT plus autologous stem-cell transplantation. The patients' demographic features, clinical characteristics, and treatment outcomes were evaluated. Statistical analyses were performed to identify risk factors associated with survival. The median age of all cohorts was 28 years. Thirty-six patients had nonseminomatous tumors, and 8 patients had seminomatous tumors. The most common primary tumor sites were the gonads (75%), followed by the mediastinum (15.9%) and the retroperitoneum (9.1%). After HDCT, 11 patients had a complete response, 12 patients had a partial response, and 17 patients had a progressive disease, respectively. About 23 patients (52.3%) experienced at least 1 treatment-related grade 3 to 4 nonhematological toxicity. About 4 patients (10%) died due to HDCT-related toxicity. The total group's median progression-free survival (PFS) was 7 months, and the median overall survival (OS) was 14.9 months. Primary tumor site (hazard ratio [HR]: 1.84; P = .028), type of HDCT regimen (HR: 0.35; P = .010), and best response to HDCT (HR: 11.0; P < .0001) were independent prognostic risk factors for PFS. The only independent prognostic risk factor associated with OS was the best response to HDCT (HR: 6.62; P = .001). The results of the study promise the best response to HDCT as a primary measure for predicting survival in relapsed/refractory GCT. In contrast, primary mediastinal GCT is not a good candidate for HDCT. Furthermore, a carboplatin-etoposide regimen in combination with cyclophosphamide and paclitaxel may improve PFS.

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Survival outcomes of patients with germ cell tumors treated with high-dose chemotherapy for refractory or relapsing disease.

Publications

Survival outcomes of patients with germ cell tumors treated with high-dose chemotherapy for refractory or relapsing disease.

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