TI-CE High-Dose Chemotherapy for Patients With Previously Treated Germ Cell Tumors: Results and Prognostic Factor Analysis

Department of Medicine, Cornell University, Итак, New York, United States
Journal of Clinical Oncology (Impact Factor: 18.43). 03/2010; 28(10):1706-13. DOI: 10.1200/JCO.2009.25.1561
Source: PubMed


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.
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.
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.
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.

  • Source
    • "The TI-CE high-dose regimen was developed more recently with the goal of targeting patients with an unfavourable prognosis with CDT 7. TI-CE consists of an initial 2 cycles of rapidly recycled paclitaxel and ifosfamide followed by stem cell collection. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Metastatic germ cell tumours (GCTs) are usually cured with cisplatin based chemotherapy and standard treatment algorithms are established. However when this treatment fails and the disease relapses, standard treatment is much more uncertain. Both conventional dose therapy (CDT) and high dose therapy (HDT) are widely used, due to the lack of conclusive data supporting one specific approach. A recent retrospective analysis focusing on this population suggested a significant benefit for HDT. Retrospective analyses are prone to bias, and therefore while this data is provocative it is by no mean conclusive. For this reason the international community is supporting a prospective randomised trial in this area comparing CDT(TIP) with sequential HDT (TICE). The planned open labelled randomised phase III study (TIGER) is due to open in 2011 and will recruit 390 patients to detect a 13% difference in 2 year progression free survival (primary endpoint). It is hoped that this large study will conclusively resolve the uncertainty which currently exists.
    Full-text · Article · Jul 2011 · Journal of Cancer
  • [Show abstract] [Hide abstract]
    ABSTRACT: A push-pull actuator for commanding the motion of the interphalangeal joints of anthropomorphic robotic hands is proposed. The actuator, based on coil springs, made of the shape-memory alloy Nitinol, is compact enough to be easily incorporated into the phalangeal structure of a robotic finger, thus eliminating the complex routing of the cables and tendons usually adopted for transmitting motion from conventional actuators (e.g. DC servomotors) to the joints. The performance of the SMA actuator is illustrated, and the concepts of temperature, strain, and stress limits for the control of the whole push-pull actuating system are emphasized. The methods adopted to improve the usually limited frequency response of SMA actuators are also described. Finally, the control of the whole system and some experimental results demonstrating promising actuator performance are discussed
    No preview · Conference Paper · Jun 1989
  • [Show abstract] [Hide abstract]
    ABSTRACT: To discuss several important developments in testicular germ cell tumors in the past year. Genomic studies are examining gene expression as possible markers for disease relapse and chemotherapy resistance. Optimal treatment strategies for early-stage nonseminomatous tumors continue to evolve and patient compliance with posttreatment surveillance schedules remains problematic. Advanced and platinum-refractory disease states continue to be challenging entities in terms of optimizing therapy and outcome. Significant challenges remain for treatment of certain categories of testicular germ cell tumors. Treatment and surveillance paradigms continue to be defined and refined as research in these areas continues.
    No preview · Article · May 2010 · Current opinion in oncology
Show more