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Abonour et al. 389
INTRODUCTION
With >7600 new cases expected to be diagnosed in 1998, germ cell tumors are
the most common cancer among young people between the ages of 15 and35
years. 1
Fortunately, the introduction of cisplatin-based combination therapy 20
years ago led to a high rate of cure; those who present with minimal to moderate
dissemination can expect a cure rate of >95%. 2
- 3
However, of the patients
presenting with more advanced disease, only 70% are cured with first-line
therapy. 4
Second-line salvage therapy, which includes vinblastine, ifosfamide,
cisplatin with or without cyclophosphamide, and dactinomycin (VIP or VAB-6), is
associated with only a 25-30% cure rate. 5
- 6
Recently, third-line salvage therapy, high-dose chemotherapy, has shown a cure
rate of 20-25%. 7-9
Although HDCT in these heavily pretreated patients is
associated with a high mortality rate (15-20%), the introduction of cytokines and
the use of PBPCs in the treatment of high-risk germ cell tumors at an earlier stage
have resulted in reduced treatment-related mortality.
HDCT is being evaluated in two settings. First, several groups are involved in
a study using HDCT as first-line therapy in the management of patients who histor­
ically have had low rates of cure. Second, we are testing HDCT as an initial salvage
therapy for those with relapsed or refractory disease after first-line cisplatin-based
regimens.
HIGH-DOSE CHEMOTHERAPY AS INITIAL THERAPY
FOR POOR-RISK PATIENTS
Since germ cell tumors are highly responsive to chemotherapy, and a doseresponse
relationship has been suggested for etoposide, cisplatin, and more
recently, carboplatin, it is logical to use such agents at higher doses for patients
with poor-prognosis disease. The early use of HDCT in this setting is intended to
bring the cure rate in line with that achieved for good-prognosis patients.
Employing this strategy in this group of patients is possible because of their young
age and ability to tolerate HDCT.
A recently published study from the Medical Research Council and the
European Organization for Research and Treatment of Cancer tested the hypothesis
that more intensive chemotherapy early in the management of patients with poorprognosis
nonseminomatous germ cell tumor may increase survival. 10
This was a
randomized trial that included 380 patients and accrued patients between May 1990
and June 1994. The first arm of the treatment consisted of three cycles of
bleomycin, vincristine, and cisplatin at 10-day intervals (BOP) followed by three
cycles of etoposide, ifosfamide, and cisplatin (VIP) with additional bleomycin after
BOP and twice in each cycle of VIP. In the second arm, four cycles of BEP were