International Journal of Urology (2007) 14, 5459 doi: 10.1111/j.1442-2042.2006.01655.

Long-term results of rst-line sequential high-dose carboplatin,

etoposide and ifosfamide chemotherapy with peripheral blood
stem cell support for patients with advanced testicular germ
cell tumor
Tsuneharu Miki,1 Yoichi Mizutani,1 Hideyuki Akaza,2 Seiichiro Ozono,3 Taiji Tsukamoto,4 Toshiro Terachi,5
Katsusuke Naito,6 Norio Nonomura,7 Isao Hara,8 Osamu Yoshida9 and The Japan Blood Cell Transplantation Study
Group for Testicular Germ Cell Tumor*
1
Department of Urology, Kyoto Prefectural University of Medicine, Graduate School of Medical Sciences, Kyoto, 2Department of Urology, University of
Tsukuba, School of Medicine, Ibaragi, 3Department of Urology, Hamamatsu University School of Medicine, Shizuoka, 4Department of Urology, Sapporo
Medical University, Hokkaido, 5Department of Urology, School of Medicine, Tokai University, Kanagawa, 6Department of Urology, Yamaguchi University,
School of Medicine, Yamaguchi, 7Department of Urology, Osaka University, Graduate School of Medicine, Faculty of Medicine, Osaka, 8Department of Urology,
Kobe University, Graduate School of Medicine, School of Medicine, Hyogo, and 9Nara Medical University, Nara, Japan

Objective: Standard chemotherapy shows relatively low long-term survival in patients with poor-risk testicular germ cell tumor (GCT). First-line
high-dose chemotherapy (HD-CT) may improve the result. High-dose carboplatin, etoposide, ifosfamide chemotherapy followed by autologous
peripheral blood stem cell transplantation (PBSCT) was investigated as rst-line chemotherapy in patients with advanced testicular GCT.
Methods: Fifty-ve previously untreated testicular GCT patients with Indiana advanced disease criteria received three cycles of bleomycin,
etoposide and cisplatin (BEP) followed by one cycle of HD-CT plus PBSCT, if elevated serum tumor markers were observed after three cycles of
the BEP regimen.
Results: Thirty patients were treated with BEP alone, because the tumor marker(s) declined to normal range. Twenty-ve patients received BEP
and HD-CT. One patient died of rhabdomyolysis due to HD-CT. Three and six (13% and 25%) out of 24 patients treated with BEP and HD-CT achieved
marker-negative and marker-positive partial responses, respectively. The other patients achieved no change. Fifteen (63%) are alive and 14 (58%)
are free of disease at a median follow-up time of 54 months. Severe toxicity included treatment-related death (4%).
Conclusions: HD-CT with peripheral stem cell support can be successfully applied in a multicenter setting. HD-CT demonstrated modest
anticancer activity for Japanese patients with advanced testicular GCT and was well tolerated. This regimen might be examined for further
investigation in randomized trials in rst-line chemotherapy for patients with poor-risk testicular GCT.

Key words: chemotherapy, germ cell tumor, high-dose, peripheral blood stem cell transplantation (PBSCT), testis.

Introduction Cancer Collaborative Group classification show survival rates of only

Cisplatin-based combination chemotherapy has improved the progno-
sis of patients with metastatic germ cell tumor (GCT), and the long-
term cure rate is approximately 80%.1,2 However, patients with the
advanced disease criteria according to the Indiana University classi-
fication or the poor prognosis criteria of the International Germ Cell
Correspondence: Tsuneharu Miki, MD, Department of Urology, Kyoto Pre-
fectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto
602-8566, Japan. Email: tmiki@koto.kpu-m.ac.jp
*Japan Blood Cell Transplantation Study Group for Testicular Germ Cell
Tumor: Sapporo Medical University, Yamagata University, Tohoku University,
Jichi Medical School, University of Tsukuba, Ibaraki Prefectural Central
Hospital, Chiba University, The Jikei University, Nippon Medical School,
Tokyo Womens Medical University, Kyorin University, Nagaoka Chuo
General Hospital, Niigata Cancer Center, Nagoya Daini Red Cross Hospital,
Shiga University of Medical Science, Nara Medical University, Kyoto Uni-
versity, Kyoto Prefectural University of Medicine, Aiseikai Yamashina Hospi-
tal, Kansai Medical University, Osaka University, Osaka City University,
Seichokai Fuchu Hospital, Japanese Red Cross Wakayama Medical Center,
Kobe University, Kobe City General Hospital, Kawasaki Medical School,
Hiroshima University, Yamaguchi University, Ehime University, University of
the Ryukyu.
Received 30 January 2006; accepted 19 July 2006.
5060% following standard-dose cisplatin-based chemotherapy.35
Several attempts have been undertaken to improve the outcome of this
patient group, including the use of double-dose cisplatin regimens or
alternating dose-dense chemotherapy sequences.68 However, doubling
the dose of cisplatin did not lead to an improved outcome as compared
with a standard cisplatin-dose regimen. Recently, high-dose chemo-
therapy (HD-CT) followed by autologous peripheral stem cell support
or autologous bone marrow support has also been studied in these
patients.911 The rationale for the use of HD-CT in patients with GCT is
based on preclinical and clinical data suggesting a doseresponse rela-
tionship for certain drugs used in the treatment of GCT, particularly for
etoposide and ifosfamide.12,13 Dose finding studies in the high-dose
setting, usually using a combination of carboplatin, etoposide and
cyclophosphamide, ifosfamide, or thiotepa, have been conducted in
heavily pretreated patients with relapsed or refractory disease.14,15
Although single center phase II trials have reported 2-year survival
rates of 7080% using first-line HD-CT approaches in poor prognosis
patients, results of large phase II trials or phase III trials are lacking.911
In addition, it is unclear at present whether the reported survival rates
of 7080% are maintained with longer follow up. The present study
investigated the long-term results of first-line HD-CT with autologous
stem cell support in Japanese patients with advanced testicular GCT in
a multicenter setting. Patients with relapsed testicular GCT were
excluded in this study.

54 2007 The Japanese Urological Association


Methods
Patients
Fifty-five patients with advanced testicular GCT were entered onto this
institutional review board-approved prospective trial between March
1996 and December 1999. All patients gave informed consent before
they were enrolled onto the study.
Eligibility included advanced disease criteria according to the
Indiana classification.3 According to the International Germ Cell
Cancer Collaborative Group (IGCCCG) criteria, the numbers of good ,
intermediate and poor prognosis were 7, 26 and 22, respectively. All
patients had histologically confirmed testicular GCT and no prior che-
motherapy. Patients were also required to have a pretreatment leukocyte
count greater than 3000/mL, pretreatment platelet count greater than
100 000/mL, glomerular filtration rate of 60 mL/min or higher, and
serum creatinine level less than or equal to 1.5 times the upper level of
the institutional norm.
Before chemotherapy, each patient was evaluated with a history and
physical examination, chest radiography, computed tomography (CT)
of the abdomen/pelvis, and screening chemistries, which included
serum tumor markers (alpha-fetoprotein [AFP], human chorionic
gonadotropin-b [HCG-b] and lactate dehydrogenase [LDH]). CT of
chest or brain and bone scintigraphy were performed as indicated. All
patients had chest CT, if chest X-ray suggested metastases.
Mobilization and harvest of peripheral blood stem
cells
A dose of 5 mg/kg of recombinant human granulocyte colony-
stimulating factor (G-CSF) was given to each patients s.c. once daily
from the day of the nadir of neutrophil count after bleomycin, etoposide
and cisplatin (BEP) combination chemotherapy. After white blood cells
(WBC) recovered to 5000/mL, leukapheresis collections of peripheral
blood stem cells were carried out for 23 consecutive days using a CS
3000 blood cell separator (Baxter Limited , Deerfields, IL, USA). A
total volume of 1015 L of blood was processed in each patient. Mono-
nuclear cells containing hematopoietic stem/progenitor cells were cryo-
preserved in liquid nitrogen. The target harvest was more than 2.0 106
CD34-positive nucleated cells/kg patient bodyweight.
Conventional-dose chemotherapy
All patients were treated with three cycles of BEP as induction chemo-
therapy. The doses of anticancer agents, treatment schedule and
treatment-related toxicity have been described previously (bleomycin
30 mg, i.v., days 2, 9, 16; etoposide 100 mg/m2, i.v., days 15; cisplatin
20 mg/m2, i.v., days 15).16 After three cycles of BEP therapy, patients
whose tumor marker(s) were still elevated received one cycle of
HD-CT with peripheral blood stem cell transplantation (PBSCT). If the
serum tumor markers declined to normal range, the patients did not
receive HD-CT.
High-dose chemotherapy
For treatment with HD-CT and autologous PBSCT, performance status
0 or 1 was required. HD-CT consisted of 1250 mg/m2 of carboplatin,
1500 mg/m2 of etoposide, and 7.5 g/m2 of ifosphamide followed by
300 mg/m2 of Mesna (bolus i.v. every 8 h, days 15). HD-CT was
administered in five divided doses from day -7 to day -3. PBSCT was
given i.v. on day 0. All patients received 5 mg/kg of G-CSF s.c., begin-
2007 The Japanese Urological Association
High-dose chemotherapy for testicular GCT
ning the day following PBSCT and continuing until neutrophil count
recovery. If all abnormally elevated serum tumor marker values
returned to normal, surgery was performed when it was necessary to
resect residual tumors.
Evaluation procedures
Serum tumor markers were determined before each treatment cycle and
4 weeks after the end of therapy. Evaluation of measurable disease by
radiographic means was performed after HD-CT cycle and 46 weeks
after the end of treatment. Subsequent follow-up tests including CT
scans, serum tumor marker values and routine blood tests were per-
formed at 3-month intervals during the first 2 years and then every
6 months up to 5 years of follow up.
Response to first-line HD-CT was defined according to World Health
Organization (WHO) criteria.17 Complete response (CR) was defined as
the disappearance of all evidence of disease for at least 6 weeks when
documented by imaging and all tumor markers. Partial response (PR)
was defined as at least 50% reduction in the product of perpendicular
diameters of each indicator lesion. PR was divided into two categories,
partial response with tumor marker normalization (PRm) and marker
positive partial response (PRm+). Progressive disease (PD) was defined
as 25% increase in the product from any lesion or the appearance of any
new lesion. No change (NC) was defined as that which did not meet any
of the above criteria. NC was also divided to two categories, no change
with tumor marker normalization (NCm) and marker positive no
change (NCm+). Response and duration of survival were measured from
the date of initiation of HD-CT.
Statistical analysis
Disease-specific survival was determined by the KaplanMeier
method. For statistical analysis, a c2 test was used.
Results
Patient characteristics
Fifty-five patients, ranging in age 1651 years (median, 27 years), were
entered into this trial. Patient characteristics are summarized in
Table 1a. Approximately 75% of all patients had lung metastasis and
involvement of abdominal lymph nodes. Liver metastasis was present
in 20% of patients. Four percent of patients had bone metastasis and 7%
had central nervous system metastasis at diagnosis. Their histological
types of GCT were four pure seminomas and 51 non-seminomas.
Response and survival
Five of 55 patients treated with three cycles of BEP achieved CR.
Twenty-five of 50 patients who achieved PR or NC by induction BEP
had normal concentrations of serum tumor markers. These 30 patients
received another cycle of BEP therapy
Thus, following three cycles of induction BEP therapy, the remain-
ing 25 patients whose tumor marker(s) (AFP, HCG-b and/or lactate
dehydrogenase [LDH]) were still elevated when treated with one cycle
of HD-CT with PBSCT. The patient characteristics are summarized in
Table 1b. According to the IGCCCG criteria, the numbers of good ,
intermediate and poor prognoses were 1, 11 and 13, respectively.
Because one patient died of rhabdomyolysis due to HD-CT, 24 patients
were available to evaluate. Table 2 and Figure 1 summarize the
outcome data. No patient achieved CR after one cycle of HD-CT. In all,
55
T MIKI ET AL.

Table 1 Patient characteristics Table 2 Outcome data

Characteristics No. of patients Outcome No. of patients (%)

(a) Partial response 9 (37.5)

Patients age (years) 55 Marker-negative 3 (12.5)
Median 27 Marker-positive 6 (25.0)
Range 1651 No change 15 (62.5)
Histology Marker-negative 4 (16.7)
Seminoma 4 Marker-positive 11 (45.8)
Non-seminoma 51 Overall response rate 37.5
Number of metastatic sites
1 8
2 36
3 or more 11
Sites of metastasis 100
Lung 48
Retroperitoneal lymph node 45
Mediastinal lymph node 12

Survival Rate (%)

Supraclavicular lymph node 3
Liver 11
Brain 4 50

Bone 2
Serum tumor markers
HCG-b (ng/mL)
Median elevated value 42
Range 0.1120 000
0
AFP (ng/mL) 1 2 3 4 5
Median elevated value 205 Years from start of HD-CT
Range 1062 274
LDH (IU/L) Fig. 1 Disease-specic survival of testicular germ cell tumor (GCT)
Median elevated value 1 550 patients treated with high-dose chemotherapy (HD-CT). Disease-specic
Range 2137 479 survival rate was determined by the KaplanMeier method.
(b)
Patients age (years) 25
Median 27
Range 1645 nine (38%) of 24 patients achieved PR. Marker-negative PR were
Histology achieved in only three patients. Fifteen NC and no PD were observed.
Seminoma 1 Seven patients showed high serum levels of AFP before HD-CT. The
Non-seminoma 24 serum levels of AFP in six patients decreased after chemotherapy, but
Number of metastatic sites the levels in three patients were higher than normal range. In addition,
1 5
serum AFP levels in one patient increased after HD-CT. Nineteen
2 13
patients had high levels of serum HCG-b. The high serum HCG-b
3 or more 7
Sites of metastasis levels in five patients became less than the sensitivity of examination
Lung 24 after HD-CT. Although the levels of serum HCG-b in 11 patients
Retroperitoneal lymph node 19 decreased after HD-CT, the serum levels were higher than normal
Mediastinal lymph node 5 range. The increased and same serum HCG-b levels in one and two
Liver 8 patients were observed after HD-CT. Five patients demonstrated high
Brain 2 serum LDH levels. The serum LDH level in three patients decreased to
Serum tumor markers normal range after HD-CT, and the levels in the other two patients
HCG-b (ng/mL) decreased , but to more than normal range.
Median elevated value 1.35
Seventeen of 24 patients underwent operations for residual tumors.
Range 0.29.59
The patients included eight PR (marker-negative PR, three; marker-
AFP (ng/mL)
Median elevated value 52 positive PR, five) and nine NC (marker-negative NC, four; marker-
Range 92 383 positive NC, five). Salvage surgery was performed for 10 patients (five
LDH (IU/L) PR and five NC) with positive marker(s). The pathological examina-
Median elevated value 548 tions revealed nine necrosis (marker-negative, three; marker-positive,
Range 419781 six), one mature teratoma (marker-negative, one) and seven viable
Follow-up (months) malignant tumors (marker-negative, three; marker-positive, four).
Median 54 Twenty-one patients received additional therapy after first-line
Range 1080 HD-CT and/or surgical resection of residual masses. Three patients
received additional HD-CT, and nine patients received salvage chemo-
AFP, alpha-fetoprotein; HCG-b: human chorionic gonadotropin-b; LDH,
therapy with VIP (etoposide, ifosfamide and cisplatin), taxol or camp-
lactate dehydrogenase.
tothecin, and radiation.

56 2007 The Japanese Urological Association

 High-dose chemotherapy for testicular GCT

24 thrombocytopenia/anemia were reported in all patients. The

Table 3 Relationship between survival and various characteristics median duration of thrombocytopenia less than 20 000/mL was 9 days
Characteristics Outcome (patient no.)
(018 days). All patients received platelet transfusions during HD-CT.
The median amount of platelet transfusion was 55 units (20200 units).
Alive (n = 15) Dead (n = 9) Twenty patients received red blood cell transfusions during the chemo-
therapy. The median amount of transfusion was 4 units (011 units).
Serum tumor marker after HD-CT: Discontinuity of chemotherapy was not necessary for this hematologi-
Positive 10 7 cal toxicity.
Negative 5 2 As expected , the other most common non-hematological side-effects
IGCCCG criteria: were mucositis and nausea/vomiting. Diarrhea was also common. The
Good 1 0 most frequent grade 3/4 complications were nausea/vomiting, which
Intermediate 5 6 were sufficiently controlled with anti-emetic therapy. Severe neurotox-
Poor 9 3 icity was rare.
Histology: choricarcinoma No specific investigations regarding late toxicity have yet been
(+) 7 3
performed. At present, no patient developed therapy-related secondary
() 8 6
leukemia.
Histology: yolk sac tumor
(+) 5 4
() 10 5 Discussion
There was no statistical signicance by c2 test. HD-CT, high-dose chemo-
This study on first-line chemotherapy with HD-CT/PBSCT consisting
therapy; IGCCCG, International Germ Cell Cancer Collaborative Group. of carboplatin, etoposide and ifosfamide was carried out in cooperation
with 30 centers within the Japan Blood Cell Transplantation Study
Group. The objectives of this trial were to determine the outcome,
feasibility and toxicity of HD-CT/PBSCT in a multicenter setting. The
rationale for HD-CT is based on the assumption that the front-line use
Table 4 Adverse events of HD-CT may induce cell death in a higher fraction of sensitive and
intermediate-sensitive GCT before drug resistance develops. This
Adverse events Grade
assumption is based on the observation in several solid tumor types
0 1 2 3 4 including lymphomas and testicular cancer, that applying chemo-
therapy with a higher dose-intensity may lead to improved outcome.18,19
Neutropenia 0 0 0 1 22
Several phase II studies on the use of first-line HD-CT in testicular
Thrombocytopenia 0 0 3 4 16
GCT have investigated schedules consisting of two to three standard-
Anemia 0 0 11 6 6
dose cycles followed by high-dose cycles.911 These phase II studies
Fever 19 2 2 0 0
have reported 2-year survival rates of 7080% following first-line
Mucositis 7 6 9 1 0
Nausea/vomiting 1 6 8 8 0 HD-CT, indicating that a 1520% survival advantage may be achiev-
Diarrhea 11 5 6 1 0 able with first-line HD-CT as compared with standard BEP therapy.911
Liver toxicity 13 4 4 1 1 In the phase II study, Motzer et al. demonstrated that first-line high-
Renal toxicity 21 1 0 1 0 dose chemotherapy is well tolerated , and suggested a survival advan-
Skin 20 2 1 0 0 tage following this approach compared to a historical control group
treated with vinblastine, actinomycin-D, cyclophosphamide, cisplatin
and bleomycin.9 In a subsequent trial by the same investigators, poor
prognosis patients with insufficient marker decline following two
cycles of standard-dose VIP therapy received two cycles of high-dose
The median duration of follow up is 54 months with a range of carboplatin, etoposide and cyclophosphamide therapy followed by
980 months. Fourteen patients are currently alive and free of GCT autologous stem cell support. Among 58 patients treated with this
and one patient remains alive with disease. All six patients with approach, 50% remained disease-free as compared to 25% of control
marker-positive status after HD-CT, whose pathological examinations patients who only received standard-dose therapy.10 The present study
of salvage surgery revealed necrosis, are alive. Nine have died of demonstrated that first-line HD-CT with PBSCT achieved a 37.5%
disease. The 3-year and 5-year survival rates were approximately 75% response rate, with NC in another 62.5% of patients, and that the 2-year
and 63%, respectively (Fig. 1). There was no correlation between sur- survival rate was 75% following this chemotherapy. This result is
vival and various characteristics (Table 3). comparable to those phase II studies.
The only randomized study investigating HD-CT as part of the first
Adverse effects line chemotherapy for poor-risk GCT applied HD-CT with autologous
bone marrow transplantation as consolidation after three cycles at
Table 4 describes the toxicity in this study according to the WHO scale. standard doses was by Chevreau et al.20 In this study, patients received
There was a toxic death caused by rhabdomyolysis due to HD-CT. four cycles of cisplatin, etoposide, vinblastine and bleomycin (PVeVB)
Neutropenia was significant in all patients, and all patients except at standard doses or three cycles of PVeVB followed by one cycle of
one experienced WHO grade 4 neutropenia. Nine patients had neutro- high-dose cisplatin, etoposide and cyclophosphamide. This study failed
penia with fever. The median duration of neutropenia less than 500/mL to demonstrate a survival advantage for the high-dose group. The
was 9 days (815 days). All patients received G-CSF, and the median results of this trial are difficult to interpret, because the standard
duration of use of G-CSF was 11 days (821 days). Similarly, grade regimen contained double dose cisplatin, with approximately 30% of

2007 The Japanese Urological Association 57

T MIKI ET AL.
the patients randomized to the high-dose treatment arm not completing
high-dose therapy because of toxicity or early death. Another study has
conducted a matched pair analysis including 456 patients in which
first-line HD-CT was compared with standard-dose chemotherapy.21 An
11% improvement in the 2-year overall survival rate was demonstrated
in the HD-CT group and a multivariate analysis revealed the use of
first-line HD-CT to be an independent positive predictive factor for
improved survival. One recent phase III randomized controlled trial
failed to show improvement of three cycles of standard-dose VIP
chemotherapy followed by one cycle of HD-CT (carboplatin, etoposide
and cyclophosphamide) compared with four cycles of VIP standard-
dose chemotherapy for advanced GCT.22 These findings suggest that
first-line HD-CT might be more effective against poor prognosis tes-
ticular GCT than standard-dose chemotherapy. However, these data
including the present study are limited , and large randomized clinical
trials are necessary. There are two ongoing randomized clinical studies
comparing multicycles of HD-CT with standard-dose chemotherapy
(four cycles of BEP) for patients with poor prognostic GCT. HD-CT
arms are two cycles of BEP followed by HD-CT (carboplatin, etoposide
and cyclophosphamide), and one cycle of VIP followed by three cycles
of HD-CT (VIP), respectively. These studies will clarify the role of
HD-CT for GCT.
Overall toxicity was acceptable and the feasibility of this HD-CT
regimen was demonstrated. As expected , all patients except one devel-
oped grade 4 neutropenia, but all of them recovered fully due to the
stem cell support and G-CSF administration. Other hematological
toxicity was also universal, but was quite manageable. Although plate-
let transfusions were required in all patients, there was no evidence of
cumulative thrombocytopenia. No patient was removed from this study
because of hematological adverse effects. Apart from hematological
toxicity, side-effects consisted mainly of gastrointestinal events. Gas-
trointestinal side-effects were mostly manageable by supportive treat-
ments such as anti-emetic therapy. Rhabdomyolysis was fatal only in
one patient (4%). No septic death occurred during this study. Symp-
tomatic acute severe ototoxicity, nephrotoxicity or peripheral neuropa-
thy, which are common cisplatin-related toxicities, were rare.
Considering the high cure rate of GCT patients after first-line
HD-CT, late toxicity is of particular interest. The previous report
showed that 10% of patients suffered from late effects, mainly com-
pensated renal failure and peripheral neuropathy.23 In this study, no
specific investigations regarding persistent late complications have yet
been performed and therefore the incidence of late complications is
unclear. However, no patient developed a therapy-related leukemia,
which is an already-described serious late complication following high
cumulative etoposide doses.
The results observed for the 24 poor prognosis GCT patients with a
median follow up of nearly 4 years, demonstrate a 5-year disease-
specific survival rate of 63%. Following standard-dose therapy, it has
been known that relapses occurring more than 2 years after therapy are
rare. This appears to be similar for patients receiving first-line HD-CT
with only 12.5% of relapses occurring beyond 2 years.
The major goal of investigation for patients with poor-risk testicular
GCT is identification of more effective chemotherapy. The results con-
ducted at multiple centers in this study suggest that first-line HD-CT
plus stem cell support for poor-risk testicular GCT might have a modest
improved treatment outcome. In addition, this dose-intense chemo-
therapy is associated with relatively high but acceptable toxicity.
Furthermore, there is only a minimal risk for severe late toxicity or
secondary chemotherapy-induced cancer. However, it is necessary to
define the optimal regimen for further studies. Moreover, the identifi-
cation of prognostic factors for first-line HD-CT is needed and may be
58
applied to select patients for a favorable treatment outcome, although
HD-CT is effective for relapsed testicular GCT.24
Acknowledgments
The authors acknowledge the efforts and support of Dr Tatsuya Okano
(Department of Urology, Chiba Aoba Munincipal Hospital, Chiba,
Japan), Dr Yoshiaki Sonoda (Department of Hygiene, Kansai Medical
University, Osaka, Japan), Dr Tsutomu Nishiyama (Department of
Urology, Niigata University, Graduate School of Medical and Dental
Sciences, Niigata, Japan) and Dr Senji Hoshi (Department of Urology,
Yamagata Prefectural Central Hospital, Yamagata, Japan) as the Orga-
nizing Committee Members in the Japan Blood Cell Transplantation
Study Group for testicular germ cell tumor.
This work was partly supported by a Grant-in-Aid (No. 14370519)
from the Japanese Ministry of Education, Culture, Sports, Science and
Technology.
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