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Germ Cell Tumours
Table 2: Target Agent in the Treatment of Germ Cell Tumours
Authors (reference) Drug No. Patients RD or ARD CR PR- PR+ SD
Beer et al.
62
Arsenic trioxide 20 9 0 0 0 0
Moasser et al.
59
Tretinoin 16 16 0 0 0 0
Gold et al.
60
Isotretinoin 15 15 0 0 0 4
Rick et al.
61
Thalidomide 15 15 0 0 5 0
Motzer et al.
58
Suramin 14 14 0 0 1 0
Einhorn et al.
70
Imatinib 6 6 0 0 0 0
Pedersini
71
Imatinib 1 1 1 0 0 0
Kollmansberger
75
Trastuzumab 1 0 0 0 1 0
Mego et al.
78
Bevacizumab 1 1 0 0 0 1
Voigt et al.
77
HDCT plus bevacizumab 1 1 0 0 1 0
No. = number; HDCT = high-dose chemotherapy; RD = refractory disease; ARD = absolute refractory disease; CR = complete response; PR- = partial response marker normalised;
PR+ = partial response marker elevated; SD = stable disease.
by Miki et al., who showed the antitumour activity of irinotecan as a 1,250mg/m
2
/day on days one and eight and oxaliplatin 130mg/m
2
/day on
single agent or in combination with cisplatin on human germ cell day one every three weeks. Three of the 18 patients enrolled achieved an
tumours xenografted to nude mice.
23
objective response. The combination of gemcitabine and oxaliplatin has
demonstrated antitumour activity in heavily pre-treated patients with
The German Testicular Cancer Study Group performed a phase II study cisplatin-refractory germ cell cancer.
with irinotecan 300–350mg/m
2
every three weeks as a single agent in
patients with relapsed or cisplatin-refractory germ cell tumours.
24
Toxicity Oxaliplatin and Irinotecan
was acceptable, but the trial failed to demonstrate any activity of the Pectasides et al.
32
treated 18 cisplatin-refractory germ cell tumour
treatment as no response was observed among the 15 treated patients. patients in the third-line setting using a combination of irinotecan
80mg/m
2
/day on days one, eight and 15 and oxaliplatin 85mg/m
2
/day on
Miki et al. investigated the efficacy of irinotecan 100–150mg/m
2
/day on days one and 15. Seven patients (40%) achieved an objective response.
days one and 15 or 200–300mg/m
2
/day on day one plus cisplatin The most common toxicities were gastrointestinal: grade 3/4 diarrhoea
20mg/m
2
/day on days one to five or nedaplatin 100mg/m
2
/day on day and nausea/vomiting in 22 and 28% of patients, respectively.
one every four weeks in refractory germ cell tumour patients.
25
Twenty
patients were enrolled in the study; the response rate was 50% (two Oxaliplatin and Paclitaxel
complete and seven partial responses). Myelosuppression was the major A French group performed a phase II trial in 27 patients with refractory
toxicity, but adverse effects were manageable. disease or early relapse after cisplatin-based chemotherapy.
33
Patients
received paclitaxel 175mg/m
2
and oxaliplatin 130mg/m
2
on the same day
Gemcitabine and Paclitaxel every three weeks. Results were disappointing because only one patient
Einhorn et al. published a retrospective review of their experience with responded to the treatment. The main toxicity was haematological. The low
gemcitabine plus paclitaxel.
26
The rationale for combining the two drugs dose of paclitaxel (<225mg/m
2
) may account for this response rate.
was based on the results of phase I and II trials.
27,28
Thirty-two patients with
relapse after salvage treatment with HDCT and PBST were subsequently Oxaliplatin, Irinotecan and Paclitaxel
treated with paclitaxel 100mg/m
2
/day and gemcitabine 1,000mg/m
2
/day on The rationale for the combination of these three drugs is the activity of
days one, eight and 15 every four weeks. Ten of 32 patients (31%) achieved the doublets or of each drug used as a single agent in refractory germ
objective response (six complete responses and four partial remissions). The cell tumours. Twenty-eight patients were enrolled in a phase II trial.
34
All
main adverse events were neurological and haematological toxicities. This had received at least two cisplatin-based chemotherapy regimens. The
regimen was shown to offer long-term response. treatment schedule was as follows: irinotecan 200mg/m
2
/day on day
one, paclitaxel 80mg/m
2
/day on days one, eight and 15 and oxaliplatin
Oxaliplatin and Gemcitabine 200mg/m
2
/day on day one. Eighteen patients (64%) obtained an
The activity of the two drugs as single agents has been demonstrated in objective response (five CR, 13 PR-). This regimen was considered toxic
refractory patients and their combination has been shown to be because 68% of the patients showed signs of infection.
supra-additive in in vitro models. Based on these results, Pectasides et al.
29
and Kollmannsberger et al.
30
tested the combination in heavily pre-treated Oxaliplatin, Gemcitabine and Paclitaxel
patients in two phase II trials following the same schedule of gemcitabine The first trial with the three most active drugs, oxaliplatin plus gemcitabine
1,000mg/m
2
/day on days one and eight and oxaliplatin 130mg/m
2
/day and paclitaxel, has been published by De Giorgio et al. in nine
on day one every three weeks. Pectasides et al.
29
treated 29 cisplatin-refractory germ cell tumour patients.
35
The chemotherapy regimen
cisplatin-refractory patients, nine of whom (32%) achieved an objective had to be modified because of excessive haematotoxicity, and the authors
response. Kollmannsberger’s study
30
enrolled 35 patients, 16 of whom concluded that it was not feasible in this patient group. The German
(46%) achieved objective responses. The non-haematological side effects Testicular Cancer Study Group published a trial of the combination of the
were grade 3 neurotoxicity in three patients. Seventeen (48%) and 19 three drugs with the following schedule: gemcitabine 800mg/m
2
/day
(55%) patients developed grade 3/4 thrombocytopenia and leukocytopenia, and paclitaxel 80mg/m
2
/day on days one and eight, and oxaliplatin
respectively. One of them (3%) died as a result of therapy-related sepsis. De 130mg/m
2
/day on day one every three weeks.
36
Forty-one patients with
Giorgo et al.
31
developed a slightly different schedule: gemcitabine cisplatin-refractory disease or with relapse after HDCT and PBST were
88 EUROPEAN ONCOLOGY
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