TI-CE high-dose chemotherapy for patients with previously treated germ cell tumors: results and prognostic factor analysis

Abstract

Purpose: We previously reported a dose-finding and phase II trial of the TI-CE regimen (paclitaxel [T] plus ifosfamide [I] followed by high-dose carboplatin [C] plus etoposide [E] with stem-cell support) in germ cell tumor (GCT) patients predicted to have a poor prognosis with conventional-dose salvage therapy. We now report the efficacy of TI-CE with prognostic factors for disease-free survival (DFS) and overall survival (OS) in our full data set of 107 patients.

Patients and methods: Eligible patients had advanced GCTs with progressive disease following chemotherapy and unfavorable prognostic features (extragonadal primary site, incomplete response [IR] to first-line therapy, or relapse/IR to ifosfamide-cisplatin-based conventional-dose salvage). Univariate and multivariate analyses (MVAs) of prognostic factors were performed. The predictive ability of the Einhorn and Beyer prognostic models was assessed.

Results: Most patients were platinum refractory and had an IR to first-line chemotherapy. There were 54 (5%) complete and eight (8%) partial responses with negative markers; 5-year DFS was 47% and OS was 52% (median follow-up, 61 months). No relapses occurred after 2 years. Five (24%) of 21 primary mediastinal nonseminomatous GCTs are continuously disease free. On MVA, primary mediastinal site (P < .001), two or more lines of prior therapy (P < .001), baseline human chorionic gonadotropin > or = 1,000 U/L (P = .01), and lung metastases (P = .02) significantly predicted adverse DFS. Poor-risk patients did worse than good- or intermediate-risk patients according to both Beyer (P < .002) and Einhorn (P < .05) models.

Conclusion: TI-CE is effective salvage therapy for GCT patients with poor prognostic features. Mediastinal primary site and two or more lines of prior therapy were most predictive of adverse DFS. Beyer and Einhorn models can assist in predicting outcome.

Fig 1.

Kaplan-Meier curves of (A) disease-free survival and (B) overall survival for patients treated with paclitaxel + ifosfamide and carboplatin + etoposide high-dose chemotherapy.

Fig 2.

Kaplan-Meier curves of disease-free survival stratified by (A) Beyer risk group classification, (B) Beyer raw score, (C) Einhorn risk group classification, and (D) Einhorn risk classification with the low- and intermediate-risk cohorts combined into one group. Figures 2C and 2D include only the 73 patients who would have met criteria for high-dose chemotherapy at Indiana University.

Fig A1.

Kaplan-Meier curves of disease-free survival stratified by Einhorn risk classification for all patients for whom an Einhorn score could be calculated (n = 101), including the 28 patients with primary mediastinal nonseminomatous germ cell tumors or late relapse who were ineligible for high-dose chemotherapy at Indiana University. Einhorn low- and intermediate-risk cohorts have been combined into one group.