Annals of Oncology 10:1467-1473, 1999
© 1999 European Society for Medical Oncology
research-article |
A multi-center prospective phase II study of high-dose chemotherapy in germ-cell cancer patients relapsing from complete remission
1The Netherlands Cancer Institute Amsterdam
2Rotterdam Cancer Institute Amsterdam, The Netherlands
3Nijmegen University Hospital Amsterdam, The Netherlands
4Leiden University Hospital Amsterdam, The Netherlands
5Groningen University Hospital Amsterdam, The Netherlands
6Maastricht University Hospital Amsterdam, The Netherlands
7Academic Medical Center Amsterdam, The Netherlands
Correspondence to: S. Rodenhuis, MD, Department of Medical Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, NL-1066 CX Amsterdam, The Netherlands. E-mail: sroden{at}nki.nl
Purpose: To prospectively determine the efficacy of repeated high-dose alkylating chemotherapy to salvage patients with germ-cell tumors who relapsed after adequate first-line chemotherapy.
Patients and methods: Patients with germ-cell cancers relapsing from a first, second or third complete remission induced by chemotherapy were offered to participate in a Dutch national prospective trial with broad entry criteria. The salvage treatment began with a conventional dose of ifosfamide (4 g/m2 on day 1) and etoposide (100 mg/m2 on days 1, 2 and 3) followed by daily s.c. administration of G-CSF (10 µg/kg) until peripheral blood progenitor cells had been harvested. Immediately after bone marrow recovery, an intermediate dose chemotherapy course of carboplatin (target AUC: 10 mg ml–1 min on day 1) and etoposide (500 mg/m2 on days 1, 3 and 5) was given with G-CSF daily s.c. After bone marrow recovery, two subsequent courses of high-dose ‘CTC’ chemotherapy were given, each containing cyclophosphamide (6 g/m2), thiotepa (480 mg/m2) and carboplatin (target AUC: 20 mg ml–1 min). The high-dose chemotherapy was administered as 30–60-minute infusions, divided over 4 days and the stem-cell transplants were given 48–72 hours after the last chemotherapy infusion. Whenever possible, residual masses were resected at the end of treatment.
Results: Thirty-five patients were treated between January 1994 and October 1997. The toxicity of the treatment was manageable. Second CTC courses were administered in 25 patients and were associated with hemorrhagic cystitis and veno-occlusive disease in 3 and 4 patients, respectively. One patient who had recently undergone a partial hepatectomy, died of veno-occlusive disease. At the time of analysis, the median follow-up of the surviving patients was 37 months (range 12–56 months). The median progression-free survival for all patients was 44 months, and the median overall survival has not been reached. According to the internationally accepted criteria for predicting the outcome of salvage chemotherapy in germ-cell cancer (Beyer et al. J Clin Oncol 1996; 14: 2638–45), 30 patients had ‘good risk’ criteria. Of these, 29 received high-dose chemotherapy. Of this group, the salvage rate at two years was 65% (95% confidence interval: 49.5%–85.1%).
Conclusions: Over half of the germ-cell cancer patients relapsing from a chemotherapy-induced complete remission can be salvaged by a treatment strategy that incorporates high-dose chemotherapy, even when treatment is given in a multi-center setting. These data confirm the international prognostic model proposed by Beyer et al. in a prospectively studied, independent patient group and provide further evidence that high-dose therapy has a role in the salvage setting of patients with germ-cell cancer.
carboplatin, cyclophosphamide, germ-cell cancer, high-dose chemotherapy, thiotepa
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. H. Einhorn, S. D. Williams, A. Chamness, M. J. Brames, S. M. Perkins, and R. Abonour High-Dose Chemotherapy and Stem-Cell Rescue for Metastatic Germ-Cell Tumors N. Engl. J. Med., July 26, 2007; 357(4): 340 - 348. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Shamash, T Powles, K Mutsvangwa, P Wilson, W Ansell, E Walsh, D Berney, J Stebbing, and T Oliver A phase II study using a topoisomerase I-based approach in patients with multiply relapsed germ-cell tumours Ann. Onc., May 1, 2007; 18(5): 925 - 930. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Sonpavde, T. E. Hutson, and B. J. Roth Management of Recurrent Testicular Germ Cell Tumors Oncologist, January 1, 2007; 12(1): 51 - 61. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. V. Kondagunta and R. J. Motzer Chemotherapy for Advanced Germ Cell Tumors J. Clin. Oncol., December 10, 2006; 24(35): 5493 - 5502. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-P. Lotz, B. Bui, F. Gomez, C. Theodore, A. Caty, K. Fizazi, G. Gravis, R. Delva, J. Peny, P. Viens, et al. Sequential high-dose chemotherapy protocol for relapsed poor prognosis germ cell tumors combining two mobilization and cytoreductive treatments followed by three high-dose chemotherapy regimens supported by autologous stem cell transplantation. Results of the phase II multicentric TAXIF trial Ann. Onc., March 1, 2005; 16(3): 411 - 418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. de Jonge, A. D.R. Huitema, A. C. Tukker, S. M. van Dam, S. Rodenhuis, and J. H. Beijnen Accuracy, Feasibility, and Clinical Impact of Prospective Bayesian Pharmacokinetically Guided Dosing of Cyclophosphamide, Thiotepa, and Carboplatin in High-Dose Chemotherapy Clin. Cancer Res., January 1, 2005; 11(1): 273 - 282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. R. Huitema, M. Spaander, R. A. A. Mathot, M. M. Tibben, M. J. Holtkamp, J. H. Beijnen, and S. Rodenhuis Relationship between exposure and toxicity in high-dose chemotherapy with cyclophosphamide, thiotepa and carboplatin Ann. Onc., March 1, 2002; 13(3): 374 - 384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Strumberg, S. Brugge, M. W. Korn, S. Koeppen, J. Ranft, G. Scheiber, C. Reiners, C. Mockel, S. Seeber, and M. E. Scheulen Evaluation of long-term toxicity in patients after cisplatin-based chemotherapy for non-seminomatous testicular cancer Ann. Onc., February 20, 2002; 13(2): 229 - 236. [Abstract] [Full Text] [PDF]
|
|