High-Dose Chemotherapy in Adult Patients With Germ Cell Tumors

Ugo De Giorgi, MD, Giorgio Papiani, MD, Giuseppe Severini, MD, Giammaria Fiorentini, MD, Maurizio Marangolo, MD, Giovanni Rosti, MD


Cancer Control. 2003;10(1) 

In This Article

Abstract and Introduction

Background: Approximately 80% of patients with advanced germ cell tumors (GCTs) can be cured with cisplatin-based chemotherapy. Patients with poor-prognosis disease have a cure rate of only 50%,, whereas patients with first relapse have only a 25% chance of prolonged survival and potential cure following standard therapy. High-dose chemotherapy (HDC) is being investigated in patients with GCTs to improve the results of salvage treatment and in first-line setting for poor prognosis disease.
Methods: The authors review the results of the clinical trials that have evaluated the role of HDC in GCT patients. Data were obtained using a computer-assisted MEDLINE search, and meeting abstracts with clinical relevance in this field were hand-searched. Open randomized phase III studies are described and examined.
Results: Several phase II studies have shown a possible benefit for patients with recurrent disease, but the preliminary results of a phase III randomized trial did not demonstrate a survival advantage for HDC after three courses of standard-dose chemotherapy in the salvage therapy of patients in whom first-line treatment has failed. Three prospective, randomized trials are evaluating the role of HDC in a first-line setting.
Conclusions: New HDC strategies are emerging, involving new drugs (eg, paclitaxel), intensive induction regimens, and upfront and/or multiple courses of HDC. The evaluation of mature data of randomized trials will better define the role of HDC in this disease.

Approximately 80% of patients with advanced germ cell tumors (GCTs) are cured with first-line cisplatin-based chemotherapy.[1,2,3] Of the 20% to 30% of patients not achieving disease-free status, nearly 25% may be cured with salvage cisplatin plus ifosfamidebased chemotherapy.[4,5,6,7]

In 1997, the International Germ Cell Cancer Collaborative Group (IGCCCG) provided a prognostic classification for patients with advanced GCTs at the time of diagnosis ( Table 1 ).[8] Patients with poor prognosis GCTs were defined as those with nonseminomatous GCTs with any of the following characteristics: mediastinal primary tumor or nonpulmonary visceral metastases or elevation of beta-human chorionic gonadotropin (ßhCG to >50,000 IU/L, -fetoprotein to >10,000 ng/mL, or lactate dehydrogenase (LDH) to >10 times the upper limit of normal. The long-term survival rate in this population following standard-dose chemotherapy (SDC) and surgery, when necessary, is approximately 50%.[8,9,10] Therefore, treatment options for patients with GCTs with poor prognosis at diagnosis still need improvement.

Because GCTs are the most chemosensitive solid tumors, the concept of dose intensity has been developed to improve the results of chemotherapy in patients with poor prognosis in the first-line setting and in patients with relapsed or refractory GCTs. In the past few years, high-dose chemotherapy (HDC) has been intensively investigated in patients with GCTs, and a number of prospective randomized clinical trials are ongoing. This review presents the results of the clinical trials that have improved the outlook of HDC in GCT patients. A discussion of the recent developments in first-line and salvage HDC strategies is also included.