Salvage Treatment With Paclitaxel, Ifosfamide, and Cisplatin Plus High-Dose Carboplatin, Etoposide, and Thiotepa Followed by Autologous Stem-Cell Rescue in Patients With Relapsed or Refractory Germ Cell Cancer

Rick, Oliver; Bokemeyer, Carsten; Beyer, Jörg; Hartmann, Jörg T.; Schwella, N.; Kingreen, D.; Neureither, S.; Metzner, Bernd; Casper, Jochen; Wandt, Hannes; Hartmann, Frank; Schmoll, Hans‐Joachim; Derigs, G.; Gerl, Arthur; Berdel, Wolfgang E.; Kanz, Lothar; Siegert, W.

doi:10.1200/jco.2001.19.1.81

Cited by 134 publications

(71 citation statements)

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“…19 Salvage high-dose chemotherapy was performed in 15 patients in a multicenter trial of the GTCSG investigating the role of high-dose chemotherapy for patients with recurrent or refractory GCTs. 20 The remaining seven patients, as well as patients with recurrence of disease after salvage high-dose chemotherapy, received further palliative treatment for refractory disease with various agents such as orally administered etoposide, oxaliplatin, bendamustine, or gemcitabine within trials of the GTCSG. [21][22][23][24] The tissue samples from patients with resistant disease were derived from tumors resected at initial diagnosis (n ϭ 14), from secondary resection of residual masses containing viable tumor cells (n ϭ 4), or from metastatic tumors (n ϭ 4).…”

Section: Patients and Tissue Samplesmentioning

confidence: 99%

“…Patients characteristics are listed in Table 2. The refractory patients had received a median of three treatment regimens (range, 1-7) and of eight cisplatin-containing chemotherapy cycles (range, [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. All patients with therapyrefractory GCT have died, whereas all patients with 28 Only tumors scored as 2ϩ or 3ϩ were considered positive.…”

Section: Tumor Samplesmentioning

confidence: 99%

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Absence of c‐KIT and members of the epidermal growth factor receptor family in refractory germ cell cancer

Kollmannsberger

Mayer

Preßler

et al. 2002

Cancer

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BACKGROUNDGerm cell tumors (GCTs) in adolescent and young males are very sensitive to cisplatin‐based chemotherapy. However, 10–20% of the patients cannot be cured by currently available therapeutic options. Once a tumor does not respond to cisplatin, current therapeutic modalities offer only a chance for short palliation. Recently, new treatment options that interfere with various receptor tyrosine kinases, including c‐KIT and members of the epidermal growth factor receptor (EGFR) family, have been used successfully in chemotherapy‐resistant tumors overexpressing c‐KIT, ERB‐B2, or EGFR.METHODSWe studied the presence of c‐KIT and the four members of the EGFR family by immunohistochemistry, as well as by ERB‐B2 gene amplification using fluorescent in situ hybridization, in a series of 22 patients with cisplatin‐resistant GCTs in search of new treatment targets. The results in these refractory tumors were compared with those of 12 patients with chemosensitive GCTs diagnosed in an advanced metastatic stage.RESULTSThe data obtained in both groups did not differ in any of the investigated biologic markers. c‐KIT was detected in the one case of pure seminoma studied and in the seminomatous components of combined tumors. The presence of EGFR was restricted to trophoblastic giant cells and the syncytiotrophoblastic elements of four nonseminomas including one pure choriocarcinoma and to a secondary non–germ cell malignancy, which had developed most likely from a mature teratoma. ERB‐B2 was moderately positive in the secondary non–germ cell malignancy, in one mature teratoma component of a mixed nonseminoma, and together with EGFR in the syncytiotrophoblastic cells of a pure choriocarcinoma. Of all samples investigated, this latter case was the only one showing an amplification of the ERB‐B2 gene in the syncytiotrophoblasts. ERB‐B3 and ERB‐B4 were detected rarely.CONCLUSIONThe majority of refractory GCTs do not qualify for treatment with new biologic agents targeting the receptor tyrosine kinases EGFR, ERB‐B2, or c‐KIT. The lack of differences between the tumors of refractory and the responsive patients indicates that overexpression of any of these receptor tyrosine kinases does not contribute to a resistant phenotype in GCTs. Cancer 2002;95:301–8. © 2002 American Cancer Society.DOI 10.1002/cncr.10671

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Section: Patients and Tissue Samplesmentioning

confidence: 99%

Section: Tumor Samplesmentioning

confidence: 99%

Absence of c‐KIT and members of the epidermal growth factor receptor family in refractory germ cell cancer

Kollmannsberger

Mayer

Preßler

et al. 2002

Cancer

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“…Patients with relapsed disease after cisplatin-based first-line chemotherapy participating in the prospective German multicenter HD-CTX trial between September 1995 and October 1999 were eligible for inclusion into the PET protocol (Mead for the International Germ Cell Cancer Collaborative Group, 1997;Rick et al, 2001). All patients were treated at Tuebingen University Medical Center.…”

Section: Patients and Treatmentmentioning

confidence: 99%

“…All patients received autologous peripheral blood stem cell support and granulocyte-colony stimulating factor after HD-CTX according to treatment protocol and institutional practice. The results of this trial have been previously published (Rick et al, 2001).…”

Section: Patients and Treatmentmentioning

confidence: 99%

“…In these patients, high-dose chemotherapy (HD-CTX) with autologous hematopoietic stem cell support has been widely investigated in order to improve their outcome. Studies have suggested a potential survival improvement of 10 -20% using HD-CTX, but this survival increase has not yet been confirmed by a randomized trial (Broun et al, 1995;Motzer et al, 1996;Beyer et al, 1999;Rick et al, 2001). However, HD-CTX is associated with more frequent side effects as well as higher financial costs compared with standard-dose chemotherapy.…”

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Early prediction of treatment response to high-dose salvage chemotherapy in patients with relapsed germ cell cancer using [18F]FDG PET

et al. 2002

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To assess the ability of [ 18 F]fluorodeoxyglucose positron emission tomography for the early prediction of response in patients with relapsed metastatic germ cell tumours undergoing salvage high-dose chemotherapy. The role of positron emission tomography was compared with established means of tumour response assessment such as CT scans/MRI and serum tumour marker changes. In addition, positron emission tomography was compared with a current prognostic score which differentiates three prognostic groups with failure-free survival rates ranging from 5 -50%. [ 18 F]fluorodeoxyglucose uptake of metastases from germ cell tumours as well as CT scans and serum tumour marker were acquired after 2 -3 cycles of induction chemotherapy but before the start of high-dose chemotherapy and CT scans/serum tumour marker were compared with the baseline examinations in 23 patients with relapsed germ cell tumours. To evaluate the validity of early response prediction by positron emission tomography, radiological monitoring and serum tumour marker decline, histopathologic response after resection of residual masses and/or the clinical course over 6 months after the end of treatment (relapse vs freedom of progression) were used. Overall, 10 patients (43%) achieved a marker-negative partial remission, three (13%) a markerpositive partial remission, five (22%) a disease stabilization and five (22%) progressed during treatment. Nine patients (39%) remained progression-free over 6 months following treatment, whereas 14 (61%) progressed. The outcome of high-dose chemotherapy was correctly predicted by positron emission tomography/CT scan/serum tumour marker in 91/59/48%. Eight patients with a favourably predicted outcome by CT scans plus serum tumour marker but a positive positron emission tomography prior to high-dose chemotherapy, failed treatment. This results in the following sensitivities/specificities for the prediction of failure of high-dose chemotherapy: positron emission tomography 100/78%; radiological monitoring 43/78%; serum tumour marker 15/100%. The positive and negative predictive values of positron emission tomography were 88 and 100%, respectively. As compared with the prognostic score, positron emission tomography was correctly positive in all patients of the three risk groups who failed treatment. In addition, a negative positron emission tomography correctly predicted a favourable outcome in the good and intermediate group. [ 18 F]fluorodeoxyglucose positron emission tomography imaging can be used to assess response to chemotherapy in patients with relapsed germ cell tumours early in the course of treatment and may help to identify patients most likely to achieve a favourable response to subsequent high-dose chemotherapy. In patients with response to induction chemotherapy according to CT scans or serum tumour marker evaluation, positron emission tomography seems to add information to detect patients with an overall unfavourable outcome. It may also be a valuable addition to the prognostic model particularly in the goo...

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Testicular Cancer

Gietema¹,

Sleijfer²

2006

Drug Treatment in Urology

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Salvage Treatment With Paclitaxel, Ifosfamide, and Cisplatin Plus High-Dose Carboplatin, Etoposide, and Thiotepa Followed by Autologous Stem-Cell Rescue in Patients With Relapsed or Refractory Germ Cell Cancer

Abstract: Treatment with TIP followed by high-dose CET is feasible and can induce long-term remissions in 25% of patients with relapsed or refractory germ cell tumors. Peripheral nervous toxicity in approximately one third of patients is a disadvantage of this salvage strategy.

Cited by 134 publications

References 22 publications

Absence of c‐KIT and members of the epidermal growth factor receptor family in refractory germ cell cancer

Absence of c‐KIT and members of the epidermal growth factor receptor family in refractory germ cell cancer

Early prediction of treatment response to high-dose salvage chemotherapy in patients with relapsed germ cell cancer using [18F]FDG PET

Testicular Cancer

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