Management of Advanced Germ Cell Cancer in Patients With Unfavorable Prognosis

2005 ◽  
Vol 3 (1) ◽  
pp. 77-83
Author(s):  
Kim Margolin
Keyword(s):  
Germ Cell ◽  
Cell Cancer ◽  
Germ Cell Cancer ◽  
Phase Iii ◽  
High Dose ◽  
Inadequate Response ◽  
Cell Transplant ◽  
First Line ◽  
Prognostic Features ◽  
Line Therapy

Advanced germ cell cancer can be cured in most patients using chemotherapy with or without surgery. A small fraction of patients with nonseminomatous tumors (NSGCT) and an even smaller percentage of seminoma patients are destined to have a less favorable outcome, due to an inadequate response to first-line chemotherapy (failure to achieve remission, finding of residual viable carcinoma at post-chemotherapy surgery, or relapse after achieving a remission). Despite the apparent salvage potential for regimens containing ifosfamide or paclitaxel, no proof exists that such combinations are superior to the standard regimen of four cycles of cisplatin, etoposide, and bleomycin (PEB) in the front-line therapy of patients with advanced NSGCT. Other modifications of first-line therapy, such as the addition of paclitaxel or the use of escalated doses of cisplatin, also have failed to increase the cure rate. The use of single or tandem cycles of high-dose chemotherapy (HDT with autologous hematopoietic cell transplant [aHCT]) in various settings (for selected patients with poor prognostic features before therapy, patients predicted to have a poor outcome based on the rate of serum tumor marker decline while on therapy, and patients in relapse or failure to achieve adequate response to standard therapy) has been evaluated in many phase II and a limited number of phase III trials, which are summarized in this review. Important questions that remain to be answered include the role of new agents and the use of more sophisticated techniques to understand prognostic and predictive factors in selecting therapy for GCT.

Secondary leukemia after first-line high-dose chemotherapy for patients with advanced germ cell cancer

2004 ◽  
Vol 131 (4) ◽  
pp. 255-260 ◽  
Author(s):  
J. Wierecky ◽  
C. Kollmannsberger ◽  
I. Boehlke ◽  
M. Kuczyk ◽  
J. Schleicher ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Cancer ◽  
High Dose Chemotherapy ◽  
Germ Cell Cancer ◽  
High Dose ◽  
Secondary Leukemia ◽  
First Line

scholarly journals First-line high-dose chemotherapy ± radiation therapy in patients with metastatic germ-cell cancer and brain metastases

2000 ◽  
Vol 11 (5) ◽  
pp. 553-560 ◽  
Author(s):  
C. Kollmannsberger ◽  
C. Nichols ◽  
M. Bamberg ◽  
J.T. Hartmann ◽  
N. Schleucher ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Brain Metastases ◽  
Germ Cell ◽  
Cell Cancer ◽  
High Dose Chemotherapy ◽  
Germ Cell Cancer ◽  
High Dose ◽  
First Line

Emetic potential of daily oral etoposide

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 18618-18618 ◽  
Author(s):  
S. M. Herbert ◽  
M. J. Brames ◽  
L. H. Einhorn
Keyword(s):  
Germ Cell ◽  
Cell Cancer ◽  
Single Agent ◽  
High Dose Chemotherapy ◽  
Germ Cell Cancer ◽  
High Dose ◽  
Cell Transplant ◽  
Oral Etoposide ◽  
Recorded Data ◽  
Low Probability

18618 Background: Chemotherapy agents are classified by their degree of emetogenicity. Agents with high or moderate emetogenicity are treated with a 5HT3 antagonist + dexamethasone to mitigate acute and delayed chemotherapy-induced nausea and vomiting. Intravenous etoposide (E) has low probability of nausea and/or vomiting. However, at the 2004 Perugia International Antiemetic Consensus meeting, oral E was listed as a moderately emetogenic drug (Supp Care Cancer 13:80–84, 2005). Daily oral E has been used to treat refractory germ cell cancer. We prospectively evaluated the emetic potential of daily oral etoposide in this patient (pt.) population. Methods: Between 8/03 and 12/05, 13 male pts. with refractory germ cell cancer were treated with single agent daily oral E 50 mg/M2 day × 21 days every 4 weeks. All had progressed following cisplatin combination chemotherapy and had previously received high dose chemotherapy with carboplatin + E (intraveneously) with peripheral blood stem cell transplant. Median age was 35 (range 14 to 54). No pt. received prophylactic antiemetics. Pts. completed a 6 question Multinational Association Supportive Care Cancer (MASCC) antiemetic tool each day they received E. Intensity and duration of nausea were recorded, with 0 being none and 10 being most severe. Additionally, pts. were asked if they experienced vomiting. The number of vomiting episodes as well as any antiemetic medications were recorded. Data on 25 pts. will be presented and we currently have information on 13 pts. Results: 13 pts. completed the MASCC form. Only 2 pts. required antiemetic support. 1 pt. experienced emesis × 1 on day 1 and 1 pt. experienced emesis × 1 on day 11. 1 pt. experienced nausea on days 9 through 20 with a MASCC rating of 3–6. 1 pt. documented nausea day 1 through 21 with a MASCC rating of 1–3. 2 pts. experienced a MASCC rating of 1 of their nausea, 1 pt. on day 1 and 1 pt. on day 2. Overall, 8 of 13 pts. had no nausea or vomiting despite the absence of any antiemetics and 2 other patients had only minimal nausea for a single day. Conclusions: Daily oral E has only a low probability of emesis and does not require prophylactic antiemetics. [Table: see text]

Quality of life and late toxicities in germ-cell cancer patients after high-dose chemotherapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4600-4600
Author(s):  
Thomas Wuendisch ◽  
Regina Naermann ◽  
Joerg Beyer ◽  
Anja Lorch ◽  
Keyword(s):  
Quality Of Life ◽  
Germ Cell ◽  
Cell Cancer ◽  
High Dose Chemotherapy ◽  
Germ Cell Cancer ◽  
Phase Iii ◽  
High Dose ◽  
Life Questionnaire ◽  
Myocardial Infraction

4600 Background: The number of long term survivors after treatment for relapsed/refractory germ cell cancer (GCC) is increasing but little is known about quality of life (QOL) and late toxicities (LT). Methods: We assessed LT and QOL in GCC patients (pts), treated in a prospective, randomized, multicenter, phase III trial comparing single versus sequential high-dose chemotherapy (HDCT) (Lorch 2007). All 216 pts were asked to complete the European Organization of Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) prior to HDCT, 6 weeks after and yearly thereafter. Results were analyzed according to standard methods (Fayers 2001). In addition pts were contacted at a median of 76 months (range 45-109) after HDCT to obtain information about current social and professional activities as well as LT. Results: Among 216 pts, 92/216 (42%) were alive and without evidence of disease one year after randomization. Median age of pts was 34 years (range 15-56). A median of 4 conventional-dose cisplatin-based treatment cycles had been given prior to HDCT. Questionnaires and response to the survey were evaluable in 86/92 (93%) pts overall and in 59/86 (69%) pts more than 3 years after HDCT. Values for global health status, role functioning and emotional functioning declined during the first year after HDCT, increased in the following years, but did not reach the reference values from large samples of the general population in Norway (Hjermstad 1998). Pts after sequential HDCT scored better in a number of items (e.g. emotional-, cognitive-, social-functioning, fatigue and dyspnoea) in comparison to single HDCT including high-dose cyclophosphamide. Persisting polyneuropathy was reported in 59%, ototoxicity or tinnitus in 56%, erectile dysfunction in 24%, hypertension in 23%, hypercholesterinemia in 17%, diabetes mellitus in 6%, nephrotoxicity in 6%, myocardial infraction in 2% and second cancers in 1% of pts. Overall 82 % of pts were employed, 30% exercised regularly. Conclusions: HDCT has a negative impact on QOL, including social and professional life. Most common late toxicities were ototoxicity and polyneuropathy. Sequential HDCT without cyclophosphamide seems to result in a better outcome in respect to QOL.

Management of Refractory Germ Cell Cancer

2018 ◽  
pp. 324-329 ◽  
Author(s):  
Anja Lorch
Keyword(s):  
Prognostic Factors ◽  
Germ Cell ◽  
Cell Cancer ◽  
High Dose Chemotherapy ◽  
Tumor Burden ◽  
Germ Cell Cancer ◽  
Salvage Treatment ◽  
High Dose ◽  
First Line ◽  
Conventional Dose

Over the past 5 decades, the use of well-validated, guideline-based strategies has resulted in high cure rates in newly diagnosed patients with germ cell cancer. However, about 30% of those with metastatic disease at initial presentation will experience refractory disease. Salvage treatment is far more complex and less validated than first-line treatment because it is rare, patient cohorts are more heterogeneous, and prognostic factors seem to have greater impact. Prior to the initiation of any salvage treatment, several considerations must be made, including assessment of known prognostic factors and choice of the optimal salvage strategy. Evaluation of patients according to their disease biology, response to prior treatment, and the extent of their tumor burden at the time of salvage treatment is crucial for establishing the optimal salvage strategy. Patients with metastatic germ cell cancer in whom adequate cisplatin-based first-line chemotherapy fails should be included in the ongoing randomized TIGER trial comparing conventional-dose chemotherapy with high-dose chemotherapy as first salvage treatment. Outside this trial, patients may be treated with conventional or high-dose chemotherapy depending on the presence or absence of adverse prognostic factors, availability of resources, and patient and physician preferences.

scholarly journals High Dose Chemotherapy with Autologous Stem Cell Transplant in Treatment of Germ Cell Tumors: A Systematic Review and Meta-Analysis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5829-5829
Author(s):  
Muhammad Husnain ◽  
Irbaz Bin Riaz ◽  
Muhammad Umar Kamal ◽  
Farva Razia Gondal ◽  
Zeeshan Ali ◽  
...  
Keyword(s):  
Germ Cell ◽  
Stem Cell Transplant ◽  
Meta Analysis ◽  
Cell Cancer ◽  
Germ Cell Tumors ◽  
High Dose Chemotherapy ◽  
Germ Cell Cancer ◽  
High Dose ◽  
Cell Transplant ◽  
Poor Risk

Abstract Background: Cure rates for the poor risk, relapsed and refractory germ cell tumors are only 25 % with conventional dose chemotherapy. High Dose Chemotherapy (HDCT) followed by rescue stem cell transplant has since been studied in randomized controlled trails for the IGCCG poor risk group patients and for the relapsed and refractory testicular cancer patients. We conducted a meta-analysis of all prospective Phase II and III trials studying the role of high dose chemotherapy in germ cell tumors. Methods: Literature search was conducted using methods described in the PRISMA statement. Medline (PubMed and Ovid SP), Embase, Cochrane Central Register of Controlled Clinical Trials(CENTRAL) and Cochrane Database of Systematic Review (CDSR) were searched from the inception of these databases till present. We performed a meta-analysis using Comprehensive Meta-analysis 3.0 using random effects model. The heterogeneity was assessed using I2values and sensitivity analysis was performed to explain the heterogeneity where present. Results: After a comprehensive literature search 4440 studies were identified and finally 35 studies were included in the final analysis. 14 studies involving 905 patients with IGCCG poor risk germ cell cancer were treated with high dose chemotherapy. 44 % (398) patients were able to achieve CR with HDCT with HR of o.48 (0.33-0.62) p=0.75. The overall survival (OS) and Progression free survival (PFS ) were 0.62 (0.54-0.69, p=0.004) and 0.60 (0.52-0.68 p=0.011) respectively. 21 studies involving 1153 patients with relapsed and or refractory germ cell cancer were identified. CR rate with HDCT was 32 % (374 patients) with HR of 0.32 (0.26-0.40, p=0.00). The results for OS failed to show any significant results with HR of 0.52 (0.44-0.60, p=0.67) but was significant for PFS with HR of 0.60 (0.52-0.67, p=0.01). Conclusion: High dose chemotherapy followed by HSCT showed significant OS and PFS for IGCCG poor risk category germ cell tumors and significant CR and PFS for relapsed and or refractory germ cell cancer group. Disclosures Anwer: Incyte: Speakers Bureau; Seattle Genetics: Other: Advisory Board Participant.

scholarly journals Evaluation of second line and subsequent targeted therapies in metastatic renal cell cancer (mRCC) patients treated with first line cediranib

2014 ◽  
Vol 8 (11-12) ◽  
pp. 398 ◽  
Author(s):  
Suzanne Richter ◽  
Jo-An Seah ◽  
Gregory R Pond ◽  
Hui K Gan ◽  
Mary J. Mackenzie ◽  
...  
Keyword(s):  
Renal Cell ◽  
Kinase Inhibitor ◽  
Cell Cancer ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Pivotal Phase ◽  
Line Therapy ◽  
To Receive

Introduction: Pivotal phase III trials have positioned angiogenesis inhibitors as first-line therapy for the management of most advanced or metastatic renal cell carcinomas (mRCC). Approaches to second-line therapy, however, remain more controversial with respect to drug selection and drug sequencing.Methods: In this study we evaluated mRCC patients who were initially treated on the first-line National Cancer Institute (NCI) trial with the highly potent vascular endothelial growth factor receptor tyrosine kinase inhibitor (TKI), cediranib, to determine the efficacy and tolerability of subsequent therapies.Results: Twenty-eight (65.1%) of the 43 patients enrolled on the first-line cediranib trial were known to receive second-line therapy, most commonly sunitinib (n = 21), with 4 (14%), 2 (7%) and 1 (3%) patients receiving temsirolimus, sorafenib, and interleukin, respectively. Of these, 14 (50%) went on to have 3 or more lines of therapy. The progression-free survival (PFS) proportion (PFS) at 1 year from starting second line was 30% (14.5%–47.9%). Longer duration of first-line cediranib treatment was modestly associated with longer duration of second-line treatment (Spearman rho 0.26). Patients who discontinued cediranib for toxicity were less likely to receive second-line sunitinib.Conclusion: In this real world evaluation, sequential use of TKIs for the management of mRCC was common. PFS with sequential TKIs was similar to observed and published results for any second-line therapy. Prior toxicity affected treatment patterns and the frequent use of at least 3 lines of therapy underscores the need for prospective sequencing trials in this disease.

scholarly journals A multi-center prospective phase II study of high-dose chemotherapy in germ-cell cancer patients relapsing from complete remission

1999 ◽  
Vol 10 (12) ◽  
pp. 1467-1474 ◽  
Author(s):  
S. Rodenhuis ◽  
R. de Wit ◽  
P.H.M. de Mulder ◽  
H.J. Keizer ◽  
D.T. Sleijfer ◽  
...  
Keyword(s):  
Complete Remission ◽  
Germ Cell ◽  
Cancer Patients ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Cell Cancer ◽  
High Dose Chemotherapy ◽  
Germ Cell Cancer ◽  
High Dose ◽  
Prospective Phase
Sign in / Sign up

Export Citation Format

Share Document