Faculty Opinions recommendation of Randomized phase III study comparing paclitaxel-bleomycin, etoposide, and cisplatin (BEP) to standard BEP in intermediate-prognosis germ-cell cancer: intergroup study EORTC 30983.

Purpose To compare the efficacy of four cycles of paclitaxel–bleomycin, etoposide, and cisplatin (T-BEP) to four cycles of bleomycin, etoposide, and cisplatin (BEP) in previously untreated patients with intermediate-prognosis germ-cell cancer (GCC). Patients and Methods Patients were randomly assigned to receive either T-BEP or standard BEP. Patients assigned to the T-BEP group received paclitaxel 175 mg/m2 in a 3-hour infusion. Patients who were administered T-BEP received primary granulocyte colony-stimulating factor (G-CSF) prophylaxis. The study was designed as a randomized open-label phase II/III study. To show a 10% improvement in 3-year progression-free survival (PFS), the study aimed to recruit 498 patients but closed with 337 patients as a result of slow accrual. Results Accrual was from November 1998 to April 2009. A total of 169patients were administered BEP, and 168 patients were administered T-BEP. Thirteen patients in both arms were ineligible, mainly as a result of a good prognosis of GCC (eight patients administered BEP; six patients administered T-BEP) or a poor prognosis of GCC (one patient administered BEP; four patients administered T-BEP). PFS at 3 years (intent to treat) was 79.4% in the T-BEP group versus 71.1% in the BEP group (hazard ratio [HR], 0.73; CI, 0.47 to 1.13; P [log-rank test] = 0.153). PFS at 3 years in all eligible patients was 82.7% versus 70.1%, respectively (HR, 0.60; CI: 0.37 to 0.97) and was statistically significant (P = 0.03). Overall survival was not statistically different. Conclusion T-BEP administered with G-CSF seems to be a safe and effective treatment regimen for patients with intermediate-prognosis GCC. However, the study recruited a smaller-than-planned number of patients and included 7.7% ineligible patients. The primary analysis of the trial could not demonstrate statistical superiority of T-BEP for PFS. When ineligible patients were excluded, the analysis of all eligible patients demonstrated a 12% superior 3-year PFS with T-BEP, which was statistically significant.

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A randomized phase III study comparing standard dose BEP with sequential high-dose cisplatin, etoposide, ifosfamide (VIP) plus stem cell support in males with poor prognosis germ cell cancer (GCC): An intergroup study of EORTC, GTCSG, and Grupo Germinal (EORTC 30974).

Journal of Clinical Oncology ◽

10.1200/jco.2010.28.15_suppl.4512 ◽

2010 ◽

Vol 28 (15_suppl) ◽

pp. 4512-4512 ◽

Cited By ~ 3

Author(s):

G. Daugaard ◽

I. A. Skoneczna ◽

N. Aass ◽

R. De Wit ◽

M. De Santis ◽

...

Keyword(s):

Stem Cell ◽

Poor Prognosis ◽

Standard Dose ◽

Cell Cancer ◽

Germ Cell Cancer ◽

Phase Iii ◽

High Dose ◽

Stem Cell Support ◽

Phase Iii Study ◽

Cell Support

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Management of Advanced Germ Cell Cancer in Patients With Unfavorable Prognosis

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2005.0004 ◽

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.

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

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.4600 ◽

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.

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