Journal of Clinical Oncology, Vol 7, 932-939, Copyright © 1989 by American Society of Clinical Oncology

ARTICLES

Dose-intensive chemotherapy in refractory germ cell cancer--a phase I/II trial of high-dose carboplatin and etoposide with autologous bone marrow transplantation

CR Nichols, G Tricot, SD Williams, K van Besien, PJ Loehrer, BJ Roth, L Akard, R Hoffman, R Goulet and SN Wolff
Department of Medicine, Indiana University School of Medicine, Indianapolis.

Between September 1986 and March 1988, 33 patients with refractory germ cell cancer were entered on a phase I/II trial of two courses of high- dose carboplatin plus etoposide with autologous bone marrow support. All patients had extensive prior treatment and had either cisplatin- refractory disease (67%) defined as progression within 4 weeks of the last cisplatin dose or failed at least two cisplatin-based regimens (35%) including a cisplatin-ifosfamide salvage regimen. Patients received a fixed total dose of etoposide of 1,200 mg/m2 with each cycle. The carboplatin dose ranged from 900 mg/m2 to 2,000 mg/m2. Twenty of the 33 patients received the second cycle of therapy. Despite extensive prior therapy with cisplatin, neurotoxicity, nephrotoxicity, or hearing impairment with high-dose carboplatin and etoposide was unusual. The most common nonhematologic toxicity was moderate enterocolitis. The hematologic toxicity of this regimen was substantial at each dose level. All 53 courses were accompanied by granulocytopenic fevers. Seven of the 33 patients (21%) died from treatment. All of these deaths occurred during the granulocyte nadir, and five were related to documented sepsis. Overall, 14 of 32 patients (44%) evaluable for response obtained an objective response, including eight complete remissions. Four patients remain in complete remission, with three patients being continuously free of disease in excess of 1 year. Eight responders (including four complete remissions) had progressed while receiving cisplatin. We conclude that carboplatin and etoposide can be administered in combination at high dosages and this regimen may have curative potential for patients with germ cell tumors resistant to conventional-dose cisplatin-based therapies.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				C. Bokemeyer, K. Oechsle, F. Honecker, F. Mayer, J. T. Hartmann, C. F. Waller, I. Bohlke, and C. Kollmannsberger Combination chemotherapy with gemcitabine, oxaliplatin, and paclitaxel in patients with cisplatin-refractory or multiply relapsed germ-cell tumors: a study of the German Testicular Cancer Study Group Ann. Onc., March 1, 2008; 19(3): 448 - 453. [Abstract] [Full Text] [PDF]

				D. R. Feldman, G. J. Bosl, J. Sheinfeld, and R. J. Motzer Medical Treatment of Advanced Testicular Cancer JAMA, February 13, 2008; 299(6): 672 - 684. [Abstract] [Full Text] [PDF]

				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]

				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]

				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]

				S. Modak, S. Gardner, I. J. Dunkel, C. Balmaceda, M. K. Rosenblum, D. C. Miller, S. Halpern, and J. L. Finlay Thiotepa-Based High-Dose Chemotherapy With Autologous Stem-Cell Rescue in Patients With Recurrent or Progressive CNS Germ Cell Tumors J. Clin. Oncol., May 15, 2004; 22(10): 1934 - 1943. [Abstract] [Full Text] [PDF]

				C. Kollmannsberger, J. Beyer, R. Liersch, P. Schoeffski, B. Metzner, J.T. Hartmann, O. Rick, K. Stengele, K. Hohloch, C. Spott, et al. Combination Chemotherapy With Gemcitabine Plus Oxaliplatin in Patients With Intensively Pretreated or Refractory Germ Cell Cancer: A Study of the German Testicular Cancer Study Group J. Clin. Oncol., January 1, 2004; 22(1): 108 - 114. [Abstract] [Full Text] [PDF]

				H.-J. Schmoll, C. Kollmannsberger, B. Metzner, J.T. Hartmann, N. Schleucher, P. Schoffski, J. Schleicher, O. Rick, J. Beyer, D. Hossfeld, 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 German Testicular Cancer Study Group J. Clin. Oncol., November 15, 2003; 21(22): 4083 - 4091. [Abstract] [Full Text] [PDF]

				C. Kollmannsberger, O. Rick, H.-G. Derigs, N. Schleucher, P. Schoffski, J. Beyer, R. Schoch, H.G. Sayer, A. Gerl, M. Kuczyk, et al. Activity of Oxaliplatin in Patients With Relapsed or Cisplatin-Refractory Germ Cell Cancer: A Study of the German Testicular Cancer Study Group J. Clin. Oncol., April 15, 2002; 20(8): 2031 - 2037. [Abstract] [Full Text] [PDF]

				S. Hinton, P. Catalano, L. H. Einhorn, P. J. Loehrer Sr, T. Kuzel, D. Vaughn, and G. Wilding Phase II Study of Paclitaxel Plus Gemcitabine in Refractory Germ Cell Tumors (E9897): A Trial of the Eastern Cooperative Oncology Group J. Clin. Oncol., April 1, 2002; 20(7): 1859 - 1863. [Abstract] [Full Text] [PDF]

				J. Beyer, S. Stenning, A. Gerl, S. Fossa, and W. Siegert High-dose versus conventional-dose chemotherapy as first-salvage treatment in patients with non-seminomatous germ-cell tumors: a matched-pair analysis Ann. Onc., April 1, 2002; 13(4): 599 - 605. [Abstract] [Full Text] [PDF]

				O. Rick, C. Bokemeyer, J. Beyer, J. T. Hartmann, N. Schwella, D. Kingreen, S. Neureither, B. Metzner, J. Casper, H. Wandt, et al. Salvage Treatment With Paclitaxel, Ifosfamide, and Cisplatin Plus High-Dose Carboplatin, Etoposide, and Thiotepa Followed by Autologous Stem-Cell Rescue in Patients With Relapsed or Refractory Germ Cell Cancer J. Clin. Oncol., January 1, 2001; 19(1): 81 - 88. [Abstract] [Full Text] [PDF]

				M. Hildebrandt, O. Rick, A. Salama, W. Siegert, D. Huhn, and J. Beyer Detection of Germ-Cell Tumor Cells in Peripheral Blood Progenitor Cell Harvests: Impact on Clinical Outcome Clin. Cancer Res., December 1, 2000; 6(12): 4641 - 4646. [Abstract] [Full Text]

				W. P. Peters, R. D. Dansey, J. L. Klein, and R. D. Baynes High-Dose Chemotherapy and Peripheral Blood Progenitor Cell Transplantation in the Treatment of Breast Cancer Oncologist, February 1, 2000; 5(1): 1 - 13. [Abstract] [Full Text]

				C. Bokemeyer, A. Gerl, P. Schoffski, A. Harstrick, N. Niederle, J. Beyer, J. Casper, H.J. Schmoll, and L. Kanz Gemcitabine in Patients With Relapsed or Cisplatin-Refractory Testicular Cancer J. Clin. Oncol., February 1, 1999; 17(2): 512 - 512. [Abstract] [Full Text] [PDF]

				G. J. Bosl and R. J. Motzer Testicular Germ-Cell Cancer N. Engl. J. Med., July 24, 1997; 337(4): 242 - 254. [Full Text] [PDF]

				E. R. Broun, C. R. Nichols, P. Kneebone, S. D. Williams, P. J. Loehrer, L. H. Einhorn, and G. J. K. Tricot Long-Term Outcome of Patients with Relapsed and Refractory Germ Cell Tumors Treated with High-Dose Chemotherapy and Autologous Bone Marrow Rescue Ann Intern Med, July 15, 1992; 117(2): 124 - 128. [Abstract] [PDF]