Randomized Trial of Bleomycin, Etoposide, and Cisplatin Compared With Bleomycin, Etoposide, and Carboplatin in Good-Prognosis Metastatic Nonseminomatous Germ Cell Cancer: A Multiinstitutional Medical Research Council/European Organization for Research and Treatment of Cancer Trial

Horwich, A.; Sleijfer, Dirk; Fosså, S. D.; Kaye, Stan B.; Oliver, R.T.D.; Cullen, M. H.; Mead, G. M.; Wit, Ronald de; Mulder, P.H.M. de; Dearnaley, D.P.; Cook, Pat; Sylvester, Richard; Stenning, Sally

doi:10.1016/s0022-5347(01)63845-x

Cited by 33 publications

(40 citation statements)

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“…The time period over which our patients were treated spanned 26 years, during which time several different chemotherapy regimens were the standard of care. Although carboplatin‐based treatment has been shown to be inferior to cisplatin‐based regimens in seminoma and non‐seminomatous germ cell tumours [22,23], in patients with renal impairment precluding treatment with cisplatin, this still offers a curative option and should be considered.…”

Section: Discussionmentioning

confidence: 99%

The clinical features and management of testicular germ cell tumours in patients aged 60 years and older

Wheater¹,

Manners²,

Nolan³

et al. 2011

BJU International

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Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject ? and What does the study add? The treatment of younger men with testicular germ cell cancers is well documented with established intensive chemotherapy regimens for those with advanced disease. Although the majority of patients present in the third or fourth decade, men also present in later life. These patients are typically excluded from clinical trials and there are no contemporary published series describing their management. This series describes the management of older patients with testicular germ cell tumours at both early and advanced stages of disease. Patients with stage I seminoma can be safely managed with all recognised treatment strategies and state I non‐seminomas were managed with surveillance. Cure can still be achieved in older patients with advance germ cell tumours however chemotherapy regimens developed in younger patients must be tailored to the presence of co‐morbidity. OBJECTIVES • To review the practice of a large referral centre for the management of older patients with testicular germ cell cancer (GCC). • There are few published data available on the management of testicular GCC in elderly patients, who often have medical comorbidities and have been excluded from clinical trials. PATIENTS AND METHODS • We reviewed our prospectively collected database for patients presenting with GCC who were aged ≥60 years. • Details of presentation, management and outcome were recorded. RESULTS • In total, 60 patients aged ≥60 years were identified from 1461 patients treated with GCC from 1979–2005, representing 4% of the total population. • Median age was 67 years, 44 had seminoma (73%) and 16 had non‐seminoma histology (27%). • Stage I seminoma patients were managed with surveillance, adjuvant radiotherapy and adjuvant carboplatin. All stage I non‐seminomas underwent surveillance. • In total, 15 patients received systemic chemotherapy for metastatic disease with modified bleomycin, etoposide and cisplatin; etoposide and cisplatin; carboplatin‐based regimens; or other combinations. Toxicity was manageable, with no toxic deaths. • In total, four patients (6.7%) died of GCC. CONCLUSIONS • In elderly patients, GCC should be managed with curative intent. • Conventional therapies are tolerable for most men with stage I seminoma. In metastatic disease, comorbidity may necessitate treatment modifications. • Most patients are cured with manageable toxicity.

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Section: Discussionmentioning

confidence: 99%

The clinical features and management of testicular germ cell tumours in patients aged 60 years and older

Wheater¹,

Manners²,

Nolan³

et al. 2011

BJU International

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“…Standard treatment of advanced NCGCTs is platinum (Williams et al, 1987;Nichols et al, 1991;Horwich et al, 1997;de Wit et al, 1998). Although the GCTs are highly treatable disease with platinum based combination regimens, cure cannot be achieved in 20-30% of patients with advanced disease with first line chemotherapy (Ataergin et al, 2007;Keskin et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Despite higher toxicity none of these experimental regimens as part of first-line therapy improves outcome in patients with advanced disease and this approach is currently not recommended for patients poor risk (Kaye et al, 1998;Droz et al, 2007;Motzer et al, 2007;Daugaard et al, 2011). , 1997;Mazumdar et al, 2001). In our multicenter study which included patients with stage 2 and 3 NSGCTs, 5 years OS rates were 92% and 55% and 5 years DFS rates were 83% and 33%, respectively.…”

Section: Discussionmentioning

confidence: 99%

Predictors of outcome in patients with advanced nonseminamatous germ cell testicular tumors.

Yetişyiğit

Babacan

Ürün

et al. 2014

JCO

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Background: Predictor factors determining complete response to treatment are still not clearly defined. We aimed to evaluate clinicopathological features, risk factors, treatment responses, and survival analysis of patient with advanced nonseminomatous GCTs (NSGCTs). Materials and Methods: Between November 1999 and September 2011, 140 patients with stage II and III NSGCTs were referred to our institutions and 125 patients with complete clinical data were included in this retrospective study. Four cycles of BEP regimen were applied as a first-line treatment. Salvage chemotherapy and/or high-dose chemotherapy (HDCT) with autologous stem cell transplantation were given in patients who progressed after BEP chemotherapy. Post-chemotherapy surgery was performed in selected patients with incomplete radiographic response and normal tumor markers. Results: The median age was 28 years. For the good, intermediate and poor risk groups, compete response rates (CRR) were, 84.6%, 67.9% and 59.4%, respectively. Extragonadal tumors, stage 3 disease, intermediate and poor risk factors, rete testis invasion were associated with worse outcomes. There were 32 patients (25.6%) with non-CR who were treated with salvage treatment. Thirty-one patients died from GCTs and 94% of them had stage III disease. Conclusions: Even though response rates are high, some patients with GCTs still need salvage treatment and cure cannot be achieved. Non-complete response to platinium-based first-line treatment is a negative prognostic factor. Our study confirmed the need for a prognostic and predictive model and more effective salvage approaches.

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“…Carboplatin as monotherapy is insufficient even for a pure seminoma [23]. Also when given within a combination regimen in case of non‐seminoma, the use of carboplatin results in an inferior cure rate [24]. Furthermore, no secondary resection was performed after completion of chemotherapy despite the presence of mature teratoma in the primary histology.…”

Section: Discussionmentioning

confidence: 99%

Histopathological and molecular features of late relapses in non‐seminomas

et al. 2010

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These authors contributed equally to the work 2 These authors contributed equally to the work RESULTS• Relapse occurred after 76.5 months (median, range: 24-209 months).• The histology in relapse was pure yolk sac tumour in four of the nine patients analysed.• Three had a non-germ cell malignancy, one was a mixed non-seminoma and one was a pure mature teratoma.• One sample with non-germ cell malignancy originated from a yolk sac tumour without any evidence of teratoma.• In four of 12 evaluable patients, high-level microsatellite instability was observed.• All patients were KRAS wild-type but four showed a BRAF mutation at V600E. CONCLUSIONS• Many late relapses of germ cell tumours show pure yolk sac histology.• Non-germ cell malignancies do not necessarily develop from teratoma but can also arise from yolk sac histology.• The biology underlying chemotherapy resistance in late relapse could be related to a high incidence of microsatellite instability and BRAF mutation V600E, which were found in half of the patients. KEYWORDSgerm cell tumours, recurrence, drug resistance, neoplasm, teratoma What's known on the subject? and What does the study add? Late relapses from germ cell tumors respond poorly to systemic chemotherapy. This feature has been partly attributed to their presumed derivation from mature teratomas giving rise to secondary non-germ cell histologies that have lost the original germ cell-like behaviour.Our series demonstrates the occurrence of non-germ cell malignancies in the absence of mature teratoma and points towards microsatellite instability and BRAF-mutations as the biologic basis for chemotherapy resistance in about half of the cases.Study Type -Therapy (case series) Level of Evidence 4 OBJECTIVE• To describe the histopathological types of late relapses of germ cell tumours and to search for molecular markers associated with chemotherapy resistance. PATIENTS AND METHODS• Samples from 14 patients with late relapse from a non-seminoma were analysed.• Archival tumour tissue was gathered at intial diagnosis ( n = 9) and at relapse ( n = 9), mostly after previous treatment with chemotherapy.• In addition to routine histopathology, tumours were analysed for microsatellite instability and screened for mutations in the KRAS and BRAF genes.

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Randomized Trial of Bleomycin, Etoposide, and Cisplatin Compared With Bleomycin, Etoposide, and Carboplatin in Good-Prognosis Metastatic Nonseminomatous Germ Cell Cancer: A Multiinstitutional Medical Research Council/European Organization for Research and Treatment of Cancer Trial

Cited by 33 publications

References 3 publications

The clinical features and management of testicular germ cell tumours in patients aged 60 years and older

The clinical features and management of testicular germ cell tumours in patients aged 60 years and older

Predictors of outcome in patients with advanced nonseminamatous germ cell testicular tumors.

Histopathological and molecular features of late relapses in non‐seminomas

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