Survival outcomes and toxicity in patients 40 years old or older with relapsed metastatic germ cell tumors treated with high-dose chemotherapy and peripheral blood stem cell transplantation.
germ cell tumor
high-dose chemotherapy
prognosis
survival
testicular cancer
Journal
Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236
Informations de publication
Date de publication:
15 10 2021
15 10 2021
Historique:
revised:
26
05
2021
received:
10
02
2021
accepted:
26
05
2021
pubmed:
15
7
2021
medline:
11
3
2022
entrez:
14
7
2021
Statut:
ppublish
Résumé
High-dose chemotherapy (HDCT) plus peripheral blood stem cell transplantation (PBSCT) is effective salvage therapy for relapsed metastatic germ cell tumors (GCTs) but has potential toxicity. Historically, an age of ≥40 years has been associated with greater toxicity and worse outcomes. This is a retrospective analysis of 445 consecutive patients with relapsed GCT treated with HDCT and PBSCT with tandem cycles at Indiana University from between 2004-2017 per our institutional regimen. Kaplan-Meier methods and log-rank tests were used for progression-free survival (PFS) and overall survival (OS) analysis. A total of 329 patients were <40 years of age, whereas 116 patients were ≥40 years of age; HDCT was used as second-line therapy in 85% and 79%, respectively. Median follow-up time was 42.5 months (range, 0.3-173.4 months). Grade ≥3 toxicities were similar between either group, except for greater pulmonary (P = .02) and renal toxicity (P = .01) in the ≥40-years-of-age group. Treatment-related mortality was similar between both age groups: 10 patients (3%) in the <40-years-of-age group and 4 patients (3.5%) in ≥40-years-of-age group died from complications of HDCT. Two-year PFS for <40 years of age versus ≥40 years of age was 58.7% versus 59.6% (P = .76) and 2-year OS was 63.9% versus 61.5% (P = .93). Factors predicting worse PFS included Eastern Cooperative Oncology Group performance status ≥1, platinum refractory disease, nonseminoma histology, and not completing 2 cycles of HDCT. Age was not an independent predictor of worse outcomes. HDCT plus PBSCT is effective salvage therapy in patients ≥40 years of age with relapsed metastatic GCT. Patients ≥40 years of age experience similar rates of toxicity and treatment-related mortality as those <40 years of age.
Sections du résumé
BACKGROUND
High-dose chemotherapy (HDCT) plus peripheral blood stem cell transplantation (PBSCT) is effective salvage therapy for relapsed metastatic germ cell tumors (GCTs) but has potential toxicity. Historically, an age of ≥40 years has been associated with greater toxicity and worse outcomes.
METHODS
This is a retrospective analysis of 445 consecutive patients with relapsed GCT treated with HDCT and PBSCT with tandem cycles at Indiana University from between 2004-2017 per our institutional regimen. Kaplan-Meier methods and log-rank tests were used for progression-free survival (PFS) and overall survival (OS) analysis.
RESULTS
A total of 329 patients were <40 years of age, whereas 116 patients were ≥40 years of age; HDCT was used as second-line therapy in 85% and 79%, respectively. Median follow-up time was 42.5 months (range, 0.3-173.4 months). Grade ≥3 toxicities were similar between either group, except for greater pulmonary (P = .02) and renal toxicity (P = .01) in the ≥40-years-of-age group. Treatment-related mortality was similar between both age groups: 10 patients (3%) in the <40-years-of-age group and 4 patients (3.5%) in ≥40-years-of-age group died from complications of HDCT. Two-year PFS for <40 years of age versus ≥40 years of age was 58.7% versus 59.6% (P = .76) and 2-year OS was 63.9% versus 61.5% (P = .93). Factors predicting worse PFS included Eastern Cooperative Oncology Group performance status ≥1, platinum refractory disease, nonseminoma histology, and not completing 2 cycles of HDCT. Age was not an independent predictor of worse outcomes.
CONCLUSIONS
HDCT plus PBSCT is effective salvage therapy in patients ≥40 years of age with relapsed metastatic GCT. Patients ≥40 years of age experience similar rates of toxicity and treatment-related mortality as those <40 years of age.
Substances chimiques
Etoposide
6PLQ3CP4P3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3751-3760Informations de copyright
© 2021 American Cancer Society.
Références
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7-34.
Einhorn LJ, Donohue J. Cis-diamminedichloroplatinum, vinblastine, and bleomycin combination chemotherapy in disseminated testicular cancer. Ann Intern Med. 1997;87:293-298.
Cheng L, Albers P, Berney DM, et al. Testicular cancer. Nat Rev Dis Primers. 2018;4:29.
Murphy BR, Breeden ES, Donohue JP, et al. Surgical salvage of chemorefractory germ cell tumors. J Clin Oncol. 1993;11:324-329.
Kondagunta GV, Bacik J, Donadio A, et al. Combination of paclitaxel, ifosfamide, and cisplatin is an effective second-line therapy for patients with relapsed testicular germ cell tumors. J Clin Oncol. 2005;23:6549-6555.
Loehrer PJ Sr, Gonin R, Nichols CR, Weathers T, Einhorn LH. Vinblastine plus ifosfamide plus cisplatin as initial salvage therapy in recurrent germ cell tumor. J Clin Oncol. 1998;16:2500-2504.
Nichols CR, Tricot G, Williams SD, et al. Dose-intensive chemotherapy in refractory germ cell cancer-a phase I/II trial of high-dose carboplatin and etoposide with autologous bone marrow transplantation. J Clin Oncol. 1989;7:932-939.
Einhorn LH, Williams SD, Chamness A, Brames JM, Perkins SM, Abonour R. High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors. N Engl J Med. 2007;357:340-348.
Adra N, Abonour R, Althouse SK, Albany C, Hanna NH, Einhorn LH. High-dose chemotherapy and autologous peripheral-blood stem-cell transplantation for relapsed metastatic germ cell tumors: the Indiana University experience. J Clin Oncol. 2017;35:1096-1102.
Adra N, Althouse SK, Liu H, et al. Prognostic factors in patients with poor-risk germ-cell tumors: a retrospective analysis of the Indiana University experience from 1990 to 2014. Ann Oncol. 2016;27:875-879.
Feldman DR, Voss MH, Jacobsen EP, et al. Clinical features, presentation, and tolerance of platinum-based chemotherapy in germ cell tumor patients 50 years of age and older. Cancer. 2013;119:2574-2581.
Spermon JR, Witjes JA, Kiemeney LALM. Difference in stage and morphology-adjusted survival between young and elderly patients with a testicular germ cell tumor. Urology. 2002;60:889-893.
Miller RE, Markt SC, O’Donnell E, et al. Age >=40 years is associated with adverse outcome in metastatic germ cell cancer despite appropriate intended chemotherapy. Eur Urol Focus. 2017;3:621-628.
Hanna NH, Einhorn LH. Testicular cancer-discoveries and updates. N Engl J Med. 2014;371:2005-2016.
Feldman DR, Bosl GJ, Sheinfeld J, Motzer RJ. Medical treatment of advanced testicular cancer. JAMA. 2008;299:672-684.
Bhatia S, Abonour R, Porcu P, et al. High-dose chemotherapy as initial salvage chemotherapy in patients with relapsed testicular cancer. J Clin Oncol. 2000;18:3346-3351.
Cooper MA, Einhorn LH. Maintenance chemotherapy with daily oral etoposide following salvage therapy in patients with germ cell tumors. J Clin Oncol. 1995;13:1167-1169.
Miller JC, Einhorn LH. Phase 2 study of daily oral etoposide in refractory germ cell tumors. Semin Oncol. 1990;17(suppl 2):36-39.
International Germ Cell Cancer Collaborative Group. International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. J Clin Oncol. 1997;15:594-603.
Albany C, Adra N, Snavely AC, et al. Multidisciplinary clinic approach improves overall survival outcomes of patients with metastatic germ-cell tumors. Ann Oncol. 2018;29:341-346.
Feldman DR, Sheinfeld J, Bajorin DF, et al. TI-CE high-dose chemotherapy for patients with previously treated germ cell tumors: results and prognostic factor analysis. J Clin Oncol. 2010;28:1706-1713.
Fossa SD, Cvancarova M, Chen L, et al. Adverse prognostic factors for testicular cancer-specific survival: a population-based study of 27,948 patients. J Clin Oncol. 2011;29:963-970.
Terbuch A, Posch F, Bauernhofer T, et al. Age as a predictor of treatment outcome in metastatic testicular germ cell tumors. Anticancer Res. 2019;39:5589-5596.
O'Sullivan JM, Huddart RA, Norman AR, et al. Predicting the risk of bleomycin lung toxicity in patients with germ-cell tumors. Ann Oncol. 2003;14:91-96.
Latcha S, Jaimes EA, Patil S, Glezerman IG, Mehta S, Flombaum CD. Long-term renal outcomes after cisplatin treatment. Clin J Am Soc Nephrol. 2016;11:1173-1179.
Brillet G, Deray G, Jacquiaud C, et al. Long-term renal effect of cisplatin in man. Am J Nephrol. 1994;14:81-84.
Bonetti A, Franceschi T, Apostoli P, et al. Cisplatin pharmacokinetics in elderly patients. Ther Drug Monit. 1994;16:477-482.
Collette L, Sylvester RJ, Stenning SP, et al. Impact of the treating institution on survival of patients with "poor-prognosis" metastatic nonseminoma. European Organization for Research and Treatment of Cancer Genito-Urinary Tract Cancer Collaborative Group and the Medical Research Council Testicular Cancer Working Party. J Natl Cancer Inst. 1999;91:839-846.
D'Souza A, Fretham C, Lee SJ, et al. Current use and trends in hematopoietic cell transplantation in the United States. Biol Blood Marrow Transplant. 2020;26:177-182.
Ruf CG, Isbarn H, Wagner W, Fisch M, Matthies C, Dieckmann K-P. Changes in epidemiologic features of testicular germ cell cancer: age at diagnosis and relative frequency of seminoma are constantly and significantly increasing. Urol Oncol. 2014;32:33.e1-6.
Dieckmann K-P, Richter-Simonsen H, Kulejewski M, et al. Testicular germ-cell tumors: a descriptive analysis of clinical characteristics at first presentation. Urol Int. 2018;100:409-419.