Paclitaxel, ifosfamide, cisplatin (TIP) for the treatment of intermediateand poor-risk nonseminomatous germ cell tumors with an inadequate decrease in tumor markers: a phase II study
https://doi.org/10.18027/2224-5057-2022-12-3
Abstract
Purpose: To evaluate efficacy of TIP (paclitaxel, ifosfamid, cisplatin) in the 1st line treatment of germ cell tumors patients with unfavorable decline of serum tumor markers after 1 cycle of the standard regimen of chemotherapy.
Patients and methods: In this phase II multicenter, nonrandomized trial, patients were enrolled from 4 centers of the Russian Federation. Patients were included if they were older than 18 years, had evidence of testicular, retroperitoneal, or mediastinal nonseminoma based on histologic findings or clinical evidence (high serum human chorionic gonadotropin or alpha-fetoprotein levels) that matched International Germ Cell Cancer Consensus Group (IGCCCG) intermediate and poor prognosis criteria. All patients got one cycle of BEP regimen (bleomycin 30 mg on days 1, 3, 5, etoposide 100 mg / m2 on days 1–5, cisplatin 20 mg / m2 on days 1–5). Patients with unfavorable serum tumor markers decline after the first cycle of chemotherapy at day 18–21 received four cycles of TIP regimen (paclitaxel 120 mg / m2 on days 1–2, ifosfamide 1500 mg / m2 on days 2–5, and cisplatin 25 mg / m2 om days 2–5, granulocyte-colony stimulating factor 5 mg / kg on days 6–15). In the presence of a residual tumor larger than 1 cm and the technical possibility of its removal, surgical treatment was performed. The primary endpoint was 1-year progression-free survival.
Results: Between 2017 and 2021, 28 patients were included in our study: seven patients with an intermediate prognosis according to IGCCCG classification and twenty-one with poor risk. Median follow-up was 15,5 months (range, 4,4–38,3 months). The 1-year progression-free survival and overall survival in intention-to-treat population were 76,6 % and 81,0 %, respectively. One-year progression-free survival and overall survival according IGCCCG classification were 100 % and 100 % for an intermediate risk patients and 68 % and 73,8 % for a poor risk, respectively. The favorable response rate (complete response + partial response with normalization STM) was observed in 19 (68 %) patients. During the follow-up period, disease progression was noted in 9 (32 %) patients, 7 (25 %) patients died, including one from an aggressive growing mature teratoma syndrome. Eleven (39 %) patients underwent surgical treatment: retroperitoneal lymph node dissection (55 %), mediastinal lymph node dissection (36 %), pulmonary resection (9 %). Pathological complete response was achieved in 6 (55 %) patients, mature teratoma — 2 (18 %), viable tumour — 3 (27 %). TIP showed acceptable safety profile and only in one case tumor lysis syndrome was observed.
Conclusions: The TIP regimen may improve the results of treatment in the first line with unfavorable decrease of serum tumor markers after the first cycle of chemotherapy, which requires further study in a randomized trial.
About the Authors
E. R. Israelyan
Pirogov Russian National Research Medical University; N. N. Blokhin National Medical Research Center of Oncology
Russian Federation
Russian Federation
Edgar R. Israelyan, clinical resident of Department Of Oncology; clinical resident Oncology Department of Drug Therapy (Chemotherapy) No. 4
Moscow
A. A. Tryakin
N. N. Blokhin National Medical Research Center of Oncology
Russian Federation
Russian Federation
Alexey A. Tryakin, MD, PhD, DSc, Deputy Director for Research, Head of Medical Oncology (Chemotherapy) Department No. 2
Moscow
A. A. Rumyantsev
N. N. Blokhin National Medical Research Center of Oncology
Russian Federation
Russian Federation
Aleksey A. Rumyantsev, MD, PhD, Oncologist, Oncology Department of Drug Therapy (Chemotherapy) No. 4
Moscow
M. Yu. Fedyanin
N. N. Blokhin National Medical Research Center of Oncology; Moscow Multidisciplinary Clinical Center «Kommunarka»
Russian Federation
Russian Federation
Mikhail Yu. Fedyanin, MD, PhD, DSc, Senior Researcher, Oncology Department of Drug Therapy (Chemotherapy) No. 2; Head, Chemotherapy Service; Scientific Advisor, National Medical and Surgical Center named after N. I. Pirogov
Moscow
A. S. Tyulyandina
N. N. Blokhin National Medical Research Center of Oncology; I. M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation
Russian Federation
Alexandra S. Tyulyandina, MD, PhD, DSc, Head of Medical Oncology (Chemotherapy) Department No. 4; Professor, Department of Oncology, N. V. Sklifosovsky Institute of Clinical Medicine
Moscow
S. A. Protsenko
N. N. Petrov Research Institute of Oncology
Russian Federation
Russian Federation
Svetlana A. Protsenko, MD, PhD, DSc, Head of the Chemotherapy and Innovative Technologies Department
St. Petersburg
A. A. Paichadze
National Medical Research Radiological Centre
Russian Federation
Russian Federation
Anna A. Paichadze, MD, PhD, Oncologist, Oncology Department of Drug Therapy (Chemotherapy)
Moscow
Yu. M. Bychkov
Russian Scientific Center of Roentgenoradiology
Russian Federation
Russian Federation
Yury M. Bychkov, MD, PhD, Head of Oncology Day Patient Department
Moscow
G. S. Yunaev
N. N. Blokhin National Medical Research Center of Oncology
Russian Federation
Russian Federation
Grigory S. Yunaev, Anesthesiologist-Intensivist, Head of the Rehabilitation and Intensive Care Department
Moscow
S. A. Tyulyandin
N. N. Blokhin National Medical Research Center of Oncology
Russian Federation
Russian Federation
Sergey A. Tyulyandin, MD, PhD, DSc, Professor, Honored Scientist of the Russian Federation, Chief Researcher
Moscow
References
1. Gillesen S., Sauve N., Collette L. et al. Predicting Outcomes in Men With Metastatic Nonseminomatous Germ Cell Tumors (NSGCT): Results From the IGCCCG Update Consortium. J Clin Oncol. 2021;39 (14): 1563-1574. DOI: 10.1200/JCO.20.03296
2. Nichols C., Catalano P., Crawford E. et al. Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study. J Clin Oncol. 1998;16 (4): 1287-93. DOI: 10.1200/JCO.1998.16.4.1287
3. Tryakin A., Fedyanin M., Kanagavel D. et al. Paclitaxel + BEP (T-BEP) regimen as induction chemotherapy in poor prognosis patients with nonseminomatous germ cell tumors: a phase II study. Urology. 2011;78 (3):620-5. DOI: 10.1016/j.urology.2011.05.005
4. Tryakin A., Fedyanin M., Sergeev U. et al. Two-weekly accelerated BEP (aBEP) regimen as induction chemotherapy in intermediate and poor prognosis patients (pts) with nonseminomatous germ cell tumors (NSGCT): Efficacy results of phase II trial. J Clin Oncol. 2015; 33 (suppl): abstr e15566. DOI: 10.1200/jco.2015.33.15_suppl.e15566
5. Droz J., Kramar A., Biron P. et al. Failure of high-dose cyclophosphamide and etoposide combined with double-dose cisplatin and bone marrow support in patients with high-volume metastatic nonseminomatous germ-cell tumours: mature results of a randomised trial. Eur Urol. 2007;51:739–48. DOI:10.1016/j.eururo.2006.10.035
6. Motzer R., Nichols C., Margolin K. et al. Phase III randomized trial of conventional-dose chemotherapy with or without high-dose chemotherapy and autologous hematopoietic stem-cell rescue as first-line treatment for patients with poor-prognosis metastatic germ cell tumors. J Clin Oncol. 2007; 25: 247–56. DOI:10.1200/JCO.2005.05.4528
7. Schmoll H., Kollmannsberger C., Metzner B. et al. Long-term results of first-line sequential high-dose etoposide, ifosfamide, and cisplatin chemotherapy plus autologous stem cell support for patients with advanced metastatic germ cell cancer: an extended phase I/II study of the GTCSG. J Clin Oncol. 2003; 21:4083–4091. DOI:10.1200/JCO.2003.09.035
8. Fizazi K., Pagliaro L., Laplanche A. et al. Personalised chemotherapy based on tumour marker decline in poor prognosis germ-cell tumours (GETUG 13): a phase 3, multicentre, randomised trial. Lancet Oncol. 2014;15:1442–50. DOI: 10.1016/S1470-2045(14)70490-5
9. Feldman D., Hu J., Srinivas S. et al. Multicenter randomized phase 2 trial of paclitaxel, ifosfamide, and cisplatin (TIP) versus bleomycin, etoposide, and cisplatin (BEP) for first-line treatment of patients (pts) with intermediateor poorrisk germ cell tumors (GCT). J Clin Oncol. 2018;36 (15 suppl): 4508-4508. DOI: 10.1200/JCO.2018.36.15_suppl.4508
10. Fizazi K., Culine S., Kramar A. et al. Early Predicted Time to Normalization of Tumor Markers Predicts Outcome in Poor-Prognosis Nonseminomatous Germ Cell Tumors. J Clin Oncol. 2004;22:3868-3876. DOI:10.1200/JCO.2004.04.008
11. International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group. J Clin Oncol. 1997;15:594-603. DOI: 10.1200/JCO.1997.15.2.594
12. Tryakin A., Fedyanin M., Matveev V. et al. Practical guidelines for the treatment of germ cell tumors in men. Malignant Tumors: RUSSCO Practice Guidelines. 2021;11 (3s2):556-585 (in Russ.). DOI: 10.18027/2224-5057-2021-11-3s2-34
13. Mego M., Rejlekova K., Svetlovska D. et al. Paclitaxel, Ifosfamide, and Cisplatin in Patients with Poor-prognosis Disseminated Nonseminomatous Germ Cell Tumors with Unfavorable Serum Tumor Marker Decline After First Cycle of Chemotherapy. The GCT-SK-003 Phase II Trial. Eur Urol Open Sci. 2021; 33:19-27. DOI: 10.1016/j.euros.2021.09.002
14. Tryakin A. A. Drug and combined treatment of nonseminoma germ cell tumors in men: thesis. M., 2015 (in Russ.).
Review
For citations:
Israelyan E.R., Tryakin A.A., Rumyantsev A.A., Fedyanin M.Yu., Tyulyandina A.S., Protsenko S.A., Paichadze A.A., Bychkov Yu.M., Yunaev G.S., Tyulyandin S.A. Paclitaxel, ifosfamide, cisplatin (TIP) for the treatment of intermediateand poor-risk nonseminomatous germ cell tumors with an inadequate decrease in tumor markers: a phase II study. Malignant tumours. 2022;12(3):11-20. (In Russ.) https://doi.org/10.18027/2224-5057-2022-12-3
Views:
784
Email this article 