Blay_edit2.qxp 6/11/08 9:45 am Page 86
Germ Cell Tumours
New Drugs in the Treatment of Germ Cell Tumours
a report by
Aude Fléchon,
1
Jean-Yves Blay
1,2
and Jean-Pierre Droz
1
1. Department of Medical Oncology, Centre Léon Bérard; 2. UJOMM Unit, Edouard Herriot Hospital, Lyon
More than 80% of patients with metastatic germ cell tumours are cured by dimers. The drug has been investigated in three phase II trials.
5–7
All patients
cisplatin-based chemotherapy (usually a bleomycin, etoposide and cisplatin were heavily pre-treated with standard chemotherapy regimens. Many had
[BEP] regimen) and surgery for residual disease.
1
Nonetheless, only 25% of cisplatin-refractory disease and received a third or subsequent line of
patients who relapse achieve long-term survival after second-line treatment. At a dose of 225
6
to 250mg/m
2
,
5
paclitaxel induced an objective
cisplatin-based chemotherapy (usually a vinblastine, ifosfamide and cisplatin response in 12 of 51 patients (23%). A response occurred in only two of 18
[VeIP] regimen).
2
Factors that predict outcome in relapsing patients include patients (11%) with doses of between 170 and 200mg/m
2
.
7
These studies
previous complete response (CR), non-mediastinal primary, low serum provided interesting results and sufficient background to include paclitaxel
tumour markers and no visceral metastasis. High-dose chemotherapy in both first-line
8
and salvage treatments.
9
(HDCT) plus peripheral blood stem cell transplantation (PBST) can help
patients who relapse after conventional chemotherapy, but has not been Paclitaxel, Ifosfamide and Cisplatin
shown to be effacious.
3
A multi-institutional retrospective study of 310 First-line Salvage Therapy
patients treated with HDCT and PBST identified prognostic factors of Paclitaxel-based combinations have been tested for standard salvage
response to HDCT and failure-free survival (FFS) in patients with relapsed chemotherapy using a paclitaxel plus ifosfamide and cisplatin (TIP) regimen
9
or cisplatin-refractory germ cell tumours.
4
This article reviews new or and in combination with sequential HDCT.
10
At the Memorial Sloan
targeted agents in relapsed or cisplatin-refractory germ cell tumours. Kettering Cancer Center (MSKCC), paclitaxel was given at a dose of
Cisplatin-refractory disease is defined as the partial response of the disease 200mg/m
2
administered as a 24-hour continuous infusion on day one of the
during cisplatin-based chemotherapy, with subsequent progression within cycle. In the German group, paclitaxel was given on day one at a dose of
four weeks of treatment. Absolute cisplatin-refractory disease is defined as 175mg/m
2
and was administered as a three-hour infusion.
11
The same dose
tumour progression during cisplatin-based chemotherapy. and schedule were used in trials published by the Medical Research Council
(MRC)
12
and Mardiak et al.
13
In the trial conducted by the French group, the
New Drugs dose of paclitaxel was 250mg/m
2
administered as a three-hour infusion.
14
At
the MSKCC, the TIP regimen
9
was administered as first-line salvage therapy
Paclitaxel in favourable-risk patients. Thirty patients were treated: the rates of CR,
Paclitaxel, a member of the taxoid family, is an antimicrotubule agent that continuous CR and non-evolutive disease (NED) were 80, 73 and 80%,
promotes the assembly and stabilisation of microtubules from tubulin respectively. Similar TIP protocols induced a CR rate of 60% in 43 patients
included in the MRC trial,
12
and 65% in the study by Mardiak et al.
13
Aude Fléchon is a board-certified Medical Oncologist at the
Léon Bérard Centre. Her primary clinical and research interest Combination of Paclitaxel and High-dose
is in urological oncology.
Chemotherapy plus Peripheral Blood Stem Cell
E: flechon@lyon.fnclcc.fr Transplantation in First-line Salvage Therapy
The German group developed a protocol with three cycles of TIP followed
by one cycle of high-dose etoposide, carboplatin and thiotepa.
11
Eighty
patients were treated: 67% were treated in the first-line salvage setting,
Jean-Yves Blay is a Professor of Medical Oncology at the 76% were cisplatin-sensitive and only 35% had achieved previous CR. One
Claude Bernard Lyon I University, Head of the UJOMM Unit at
patient experienced a toxic death and 18 patients did not receive HDCT. The
Edouard Herriot Hospital and Head of the Department of
Medical Oncology at the Léon Bérard Centre. He is Head of the
CR, continuous CR and NED rates were 35, 26 and 33%, respectively.
Cyokine and Cancer Team at the INSERM U590 Unit,
Chairman of the Soft Tissue and Bone Sarcoma Group of the
EORTC and Director of the CONTICANET Network of
The French group has developed a protocol with two cycles of epirubicin
Excellence of the Sixth Framework Programme (FP6) of the EU. plus paclitaxel followed by one cycle of high-dose cyclophosphamide and
thiotepa and two cycles of high-dose carboplatin plus etoposide (CE).
14
Jean-Pierre Droz is a Professor of Medical Oncology at the
Forty-five patients were studied. Of these, 15% were in the first-line salvage
Claude Bernard Lyon I University and an Attending Physician in
the Department of Medical Oncology at the Léon Bérard
setting (refractory disease). Only 33 patients received HDCT, of whom 22
Centre. Professor Droz is also President of the International
completed the programme. There were five treatment-related deaths. The
Society of Geriatric Oncology.
CR, continuous CR and NED rates were 22, 19 and 23%, respectively.
The MSKCC group also developed a sequential dose-intensive protocol of
chemotherapy known as TICE (two cycles of paclitaxel plus ifosfamide
86 © TOUCH BRIEFINGS 2008
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89  |  Page 90  |  Page 91  |  Page 92  |  Page 93  |  Page 94  |  Page 95  |  Page 96  |  Page 97  |  Page 98  |  Page 99