Standard chemotherapy for disseminated germ-cell tumors includes a combination of cisplatin, vinblastine, and bleomycin, but this regimen produces substantial neuromuscular toxicity. In a randomized clinical trial in 261 men with disseminated germ-cell tumors, we substituted etoposide for the vinblastine in this regimen in half the patients to compare the efficacy and toxicity of the two treatments. Among 244 patients who could be evaluated for a response, 74 percent of those receiving the regimen including vinblastine and 83 percent of those receiving the regimen including etoposide became disease-free with or without subsequent surgery (P not significant). Among the 157 patients with high tumor volume, 61 percent became disease-free on the regimen that included vinblastine, as compared with 77 percent on the regimen that included etoposide (P less than 0.05). Survival among the patients who received etoposide was higher (P = 0.048). The regimens were similar in terms of myelosuppressive effects and pulmonary toxicity. However, the etoposide regimen caused substantially fewer paresthesias (P = 0.02), abdominal cramps (P = 0.0008), and myalgias (P = 0.00002). We conclude that etoposide with cisplatin and bleomycin is superior to vinblastine with cisplatin and bleomycin in the treatment of disseminated germ-cell tumors because of diminished neuromuscular toxicity and, among patients with advanced disease, better efficacy.
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[Abstract][Full Text]
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[Abstract][Full Text]
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[Abstract][Full Text]
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[Abstract][Full Text]
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(2004). Management of Primary Malignant Germ Cell Tumor of the Mediastinum. Jpn J Clin Oncol
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[Abstract][Full Text]
Toumi, N., Chaumette-Plankaert, M.-T., Cherqui, D., de Revel, T., Duvillard, P., Theodore, C.
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[Full Text]
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[Abstract][Full Text]
Motzer, R. J., Sheinfeld, J.
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21: 4073-4074
[Full Text]
Schmoll, H.-J., Kollmannsberger, C., Metzner, B., Hartmann, J.T., Schleucher, N., Schoffski, P., Schleicher, J., Rick, O., Beyer, J., Hossfeld, D., Kanz, L., Berdel, W.E., Andreesen, R., Bokemeyer, C.
(2003). 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. JCO
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[Abstract][Full Text]
Miyazaki, J., Kawai, K., Hayashi, H., Onozawa, M., Tsukamoto, S., Miyanaga, N., Hinotsu, S., Shimazui, T., Akaza, H.
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33: 391-395
[Abstract][Full Text]
Schumer, S. T., Cannistra, S. A.
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21: 1180-1189
[Abstract][Full Text]
Kawai, K., Miyazaki, J., Tsukamoto, S., Hinotsu, S., Hattori, K., Shimazui, T., Akaza, H.
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33: 127-131
[Abstract][Full Text]
Einhorn, L. H.
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99: 4592-4595
[Abstract][Full Text]
Hinton, S., Catalano, P., Einhorn, L. H., Loehrer, P. J. Sr, Kuzel, T., Vaughn, D., Wilding, G.
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20: 1859-1863
[Abstract][Full Text]
Vaughn, D. J., Gignac, G. A., Meadows, A. T.
(2002). Long-Term Medical Care of Testicular Cancer Survivors. ANN INTERN MED
136: 463-470
[Abstract][Full Text]
Fizazi, K., Chen, I., Logothetis, C. J.
(2002). Germ-cell tumor survivors: the price for cure. Ann Oncol
13: 187-189
[Full Text]
Strumberg, D., Brugge, S., Korn, M. W., Koeppen, S., Ranft, J., Scheiber, G., Reiners, C., Mockel, C., Seeber, S., Scheulen, M. E.
(2002). Evaluation of long-term toxicity in patients after cisplatin-based chemotherapy for non-seminomatous testicular cancer. Ann Oncol
13: 229-236
[Abstract][Full Text]
Fizazi, K., Do, K.-A., Wang, X., Finn, L., Logothetis, C. J., Amato, R. J.
(2002). A 20% dose reduction of the original CISCA/VB regimen allows better tolerance and similar survival rate in disseminated testicular non-seminomatous germ-cell tumors: final results of a phase III randomized trial. Ann Oncol
13: 125-134
[Abstract][Full Text]
Dearnaley, D., Huddart, R., Horwich, A
(2001). Regular review: Managing testicular cancer. BMJ
322: 1583-1588
[Full Text]
Gough, M H, Buss, P., Wilson, T., Turton, C., Nottingham, J., Rubin, G., Horton, R., Maran, N. J, Glavin, R. J, Grunewald, R. A, Mack, C. J, Root, T., Stefanou, A., Siderov, J., de Lemos, M., Langford, N J, Martin, U, Kendall, M J, Ferner, R E, Smith, N., Burns-Cox, N., Solomon, L., Holmes, S.
(2001). Medical errors. BMJ
322: 1421-1421
[Full Text]
de Wit, R., Roberts, J. T., Wilkinson, P. M., de Mulder, P. H.M., Mead, G. M., Fossa, S. D., Cook, P., de Prijck, L., Stenning, S., Collette, L.
(2001). Equivalence of Three or Four Cycles of Bleomycin, Etoposide, and Cisplatin Chemotherapy and of a 3- or 5-Day Schedule in Good-Prognosis Germ Cell Cancer: A Randomized Study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council. JCO
19: 1629-1640
[Abstract][Full Text]
Zanetta, G., Bonazzi, C., Cantu, M. G., Locatelli, A., Bratina, G., Mangioni, C.
(2001). Survival and Reproductive Function After Treatment of Malignant Germ Cell Ovarian Tumors. JCO
19: 1015-1020
[Abstract][Full Text]
Packer, R. J., Cohen, B. H., Coney, K.
(2000). Intracranial Germ Cell Tumors. The Oncologist
5: 312-320
[Abstract][Full Text]
Motzer, R. J., Sheinfeld, J., Mazumdar, M., Bains, M., Mariani, T., Bacik, J., Bajorin, D., Bosl, G. J.
(2000). Paclitaxel, Ifosfamide, and Cisplatin Second-Line Therapy for Patients With Relapsed Testicular Germ Cell Cancer. JCO
18: 2413-2418
[Abstract][Full Text]
Mans, D. R.A., da Rocha, A. B., Schwartsmann, G.
(2000). Anti-Cancer Drug Discovery and Development in Brazil: Targeted Plant Collection as a Rational Strategy to Acquire Candidate Anti-Cancer Compounds. The Oncologist
5: 185-198
[Abstract][Full Text]
Meinardi, M. T., Gietema, J. A., van der Graaf, W. T. A., van Veldhuisen, D. J., Runne, M. A., Sluiter, W. J., de Vries, E. G. E., Willemse, P. B. H., Mulder, N. H., van den Berg, M. P., Koops, H. S., Sleijfer, D. Th.
(2000). Cardiovascular Morbidity in Long-Term Survivors of Metastatic Testicular Cancer. JCO
18: 1725-1732
[Abstract][Full Text]
Hainsworth, J. D., Lennington, W. J., Greco, F. A.
(2000). Overexpression of Her-2 in Patients With Poorly Differentiated Carcinoma or Poorly Differentiated Adenocarcinoma of Unknown Primary Site. JCO
18: 632-632
[Abstract][Full Text]
Amato, R. J., Millikan, R., Daliani, D., Wood, L., Logothetis, C., Pollack, A.
(2000). Cyclophosphamide and Carboplatin and Selective Consolidation in Advanced Seminoma. Clin. Cancer Res.
6: 72-77
[Abstract][Full Text]
Kesler, K. A., Rieger, K. M., Ganjoo, K. N., Sharma, M., Fineberg, N. S., Einhorn, L. H., Brown, J. W.
(1999). PRIMARY MEDIASTINAL NONSEMINOMATOUS GERM CELL TUMORS: THE INFLUENCE OF POSTCHEMOTHERAPY PATHOLOGY ON LONG-TERM SURVIVAL AFTER SURGERY. J. Thorac. Cardiovasc. Surg.
118: 692-701
[Abstract][Full Text]
Brewer, M., Gershenson, D. M., Herzog, C. E., Mitchell, M. F., Silva, E. G., Wharton, J. T.
(1999). Outcome and Reproductive Function After Chemotherapy for Ovarian Dysgerminoma. JCO
17: 2670-2670
[Abstract][Full Text]
Buckner, J. C., Peethambaram, P. P., Smithson, W. A., Groover, R. V., Schomberg, P. J., Kimmel, D. W., Raffel, C., O'Fallon, J. R., Neglia, J., Shaw, E. G.
(1999). Phase II Trial of Primary Chemotherapy Followed by Reduced-Dose Radiation for CNS Germ Cell Tumors. JCO
17: 933-933
[Abstract][Full Text]
Einhorn, L. H., Stender, M. J., Williams, S. D.
(1999). Phase II Trial of Gemcitabine in Refractory Germ Cell Tumors. JCO
17: 509-509
[Abstract][Full Text]
Smith, M. A., Rubinstein, L., Anderson, J. R., Arthur, D., Catalano, P. J., Freidlin, B., Heyn, R., Khayat, A., Krailo, M., Land, V. J., Miser, J., Shuster, J., Vena, D.
(1999). Secondary Leukemia or Myelodysplastic Syndrome After Treatment With Epipodophyllotoxins. JCO
17: 569-569
[Abstract][Full Text]
Mayer, R. J., Schnipper, L. E., Broder, S., Hughes-Davies, T.H., Rand, T. S., Cole, P., Rodu, B., Corey, S., Suit, H., Isselbacher, K., Chabner, B., Feldman, A., Atkins, R. N., Arlen, P. A., Noxon, C. L., Wilcken, N., Bailar, J. C., Gornik, H. L.
(1997). Winning the War on Cancer. NEJM
337: 935-938
[Full Text]
Bosl, G. J., Motzer, R. J.
(1997). Testicular Germ-Cell Cancer. NEJM
337: 242-254
[Full Text]
Droz, J.-P., Culine, S., Biron, P., Kramar, A.
(1997). High-Dose Chemotherapy in Adult Solid Tumors and Lymphoproliferative Disorders: The Need for Randomized Trials. The Oncologist
2: 83-93
[Abstract][Full Text]
Hainsworth, J. D., Greco, F. A.
(1993). Treatment of Patients with Cancer of an Unknown Primary Site. NEJM
329: 257-263
[Full Text]
Munro, A. J., Warde, P. R.
(1991). The Use of a Markov Process to Simulate and Assess Follow-up Policies for Patients with Malignant Disease: Surveillance for Stage I Nonseminomatous Tumors of the Testis. Med Decis Making
11: 131-139
[Abstract]
Williams, S. D., Blessing, J. A., Moore, D. H., Homesley, H. D., Adcock, L.
(1989). Cisplatin, Vinblastine, and Bleomycin in Advanced and Recurrent Ovarian Germ-Cell Tumors: A Trial of the Gynecologic Oncology Group. ANN INTERN MED
111: 22-27
[Abstract]
Benditt, J. O., Farber, H. W., Wright, J., Karnad, A. B.
(1988). Pulmonary Hemorrhage with Diffuse Alveolar Infiltrates in Men with High-Volume Choriocarcinoma. ANN INTERN MED
109: 674-675
[Abstract]
Trump, D. L., Bartel, E., Pozniak, M.
(1988). Nodular Pneumonitis after Chemotherapy for Germ Cell Tumors. ANN INTERN MED
109: 431-432
[Abstract]
Einhorn, L. H.
(2002). Inaugural Article: Curing metastatic testicular cancer. Proc. Natl. Acad. Sci. USA
99: 4592-4595
[Abstract][Full Text]