Therapeutic efficacy of high-dose chemotherapy with autologous stem-cell transplantation in 44 relapsed or refractory germ-cell tumor patients: A retrospective cohort study

Abstract

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.

Figure 1.

Kaplan–Meier survival curves of prognostic factors related to progression-free survival (PFS); (A) In patients with mediastinal, retroperitoneal, and gonadal germ-cell tumors, PFSs were 2.2 months, 5.9 months, and 7.3 months, respectively (P = .027). (B) Patients who received second-line high-dose chemotherapy (HDCT) had significantly longer PFS than those who received third-line or later (67.8 vs 5.9 months; P < .0001). (C) Patients receiving Carbo–PEC-Taxol had the longest PFS, followed by CE and TTC (67.8 months vs 7.0 months vs 2.1 months, P < .0001). (D) PFS was significantly longer in patients with complete response to HDCT than incomplete response and progressive disease (P < .0001).

Figure 2.

(A) Patients who received second-line high-dose chemotherapy (HDCT) had a more prolonged overall survival (OS) than those who received third-line or later (79.1% vs 19.7%, 2-year survival; P < .0001). (B) 2-year survivals were 63.5%, 45.4%, and 0.0% in patients receiving Carbo–PEC-Taxol, CE, and TTC, respectively (P = .004). (C) The relationship between response rate and survival was positively correlated (P < .0001). 2-year survival was 100% in patients with complete response, 70% in patients with incomplete response, and 7.7% in patients with progressive disease.