EDITORIAL COMMENT
1
1298 CHEMOTHERAPY IN EARLY STAGE TESTICULAR CANCER combination. Four cycles provided results equivalent to those obtained with 3 cycles.14 The subsequent trial of patients treated with 3 cycles of EP with or without bleomycin demon- strated a sigmficant increase in the number of treatment fail- ures on the EP m.15 Another theoretical approach to achieve a substantial decrease in the toxicity of chemotherapy is the use of carboplatin instead of cisplatin. However, 2 randomized stud- ies demonstrated inferior results with carboplatin compared to cisplatin.I6, 17 Consequently, omitting bleomycin in patients re- ceiving 4 cycles of EP and limiting the cumulative dose of bleomycin to 3 cycles of BEP represent 2 equivalent optimal alternatives for patients who receive primary chemotherapy for biological disease.1s I t is noteworthy that the 2 patients with active relapse had been primarily treated with either the VAB-6 or EC regimen and, therefore, they had not received optimal chemotherapy. CONCLUSIONS Primary chemotherapy yields excellent long-term results in patients with elevated serum tumor markers only after orchi- ectomy. Since results with primary retroperitoneal lymph node dissection suggest that elevated serum tumor markers usually reflect systemic metastases rather than retroperitoneal disease, primary chemotherapy using optimal regimens seems to be the most appropriate strategy to consider. REFERENCES 11. Bosl, G. J., Geller, N. L. and Bajorin, D.: Serum tumor markers and patient allocation to good-risk and poor-risk clinical trials in patients with germ cell tumors. Cancer, 67: 1299, 1991. 12. Mead, G. M.: International consensus prognostic classification for metastatic germ cell tumours treated with platinum based chemotherapy: final report of the International Germ Cell Cancer Collaborative Group. Proc. Amer. SOC. Clin. Oncol., 14: 235, abstract 615, 1995. 13. Bosl, G. J.. Geller. N. L., Bajorin. D., Leitner, S. P., Yagoda, A., Golbey, R. B., Scher, H.. Vogelzang, N. J.. Auman. J.. Carey, R., Fair, W. R., Herr, H.. Morse, M., Sogani, P. and Whitmore, W.: A randomized trial of etoposide + cisplatin versus vinblas- tine + bleomycin + cisplatin + cyclophosphamide + dactino- mycin in patients with good-prognosis germ cell tumors. J. Clin. Oncol., 6: 1231, 1988. 14. Einhorn, L. H., Williams, S. D., Loehrer, P. J., Bircer, R., Drasga, R., Omura. G. and Greco, F. A.: Evaluation of optimal duration of chemotherapy in favorable-prognosis disseminated germ cell tumors: a Southeastern Cancer Study Group protocol. J. Clin. Oncol., 7: 387. 1989. 15. Loehrer, P. J., Johnson, D. H.. Elson, P.. Einhorn. L. H. and Trump, D.: Importance of bleomycin in favorable-prognosis disseminated germ cell tumors: an Eastern Cooperative On- cology Group trial. J. Clin. Oncol., 13: 470, 1995. 16. Bajorin, D. F., Sarosdy, M. F., Pfister, D. G., Mazumdar, M., Motzer, R. J., Scher, H. I., Geller, N. L., Faur, W. R., Herr, H., Sogani, P., Sheinfeld, J., Russo, P., Vlamis, V., Carey, R., Vogelzang, N. J., Crawford, E. D. and Bosl, G. J.: Randomized trial of etoposide and cisplatin versus etoposide and carbopla- tin in uatients with eood-risk germ cell tumors: a multiinsti- 1. Einhorn, L. H.: Treatment of testicular cancer: a new and im- proved model. J. Clin. Oncol., 8 1777, 1990. 2. Davis, B. E., Herr, H. W., Fair, W. R. and Bosl, G. J.: The management of patients with nonseminomatous germ cell tu- mors of the testis with serologic disease only after orchiec- tomy. J . Urol., 152: 111, 1994. 3. Saxman, S. B., Nichols, C. R., Foster, R. S., Messemer, J. E., Donohue, J. P. and Einhorn, L. H.: The management of pa- tients with clinical stage A testicular nonseminomatous germ cell tumors and persistently elevated serologic markers. Proc. Amer. Soc. Clin. Oncol., 14: 230, 1995. 4. Droz, J . P., Kramar, A., Ghosn, M., Piot, G., Rey, A, Theodore, C., Wibault, P.. Court, B. H., Pemn, J. L., Travagli, J . P., Bellet, D., Caillaud, J. M., Pico, J . L. and Hayat, M.: Prognostic factors in advanced nonseminomatous testicular cancer. A multivariate logistic regression analysis. Cancer, 62: 564, 1988. 5. Ghosn, M., Droz, J. P., Theodore, C., Pico, J. L., Baume, D., Spielmann, M., Ostronoff, M., Moran, A., Salloum, E., Kramar, A. and Hayat, M.: Salvage chemotherapy in refractory germ cell tumor with etoposide (VP-16) plus ifosfamide plus high- dose cisplatin. A VIhP regimen. Cancer, 63: 24, 1988. 6. Droz, J. P., Pico, J. L., Ghosn, M., Gouyette, A., Baume, D., Piot, G., Ostronoff, M., Theodore, C., Beaujean, F. and Hayat, M.: Long-term survivors after salvage high dose chemotherapy with bone marrow rescue in refractory germ cell cancer. Eur. J. Cancer, 27: 831, 1991. 7. Einhorn, L. H., Weathers, T., Loehrer, P. and Nichols, C.: Second line chemotherapy with vinblastine, ifosfamide, and cisplatin after initial chemotherapy with cisplatin, VP-16, and bleomy- cin in disseminated germ cell tumors. Proc. Amer. SOC. Clin. Oncol.. 11: 196, abstract 599, 1992. 8. Ibrahim, A,, Zambon, E., Bourhis, J. H., Ostronoff, M., Beaujean, F., Viens, P., Lhomme, C., Chazard, M., Maraninchi, D., Hayat, M., Droz, J. P. and Pico, J . L.: High-dose chemotherapy with etoposide, cyclophosphamide and escalating dose of car- boplatin followed by autologous bone marrow transplantation in cancer patients. A pilot study. Eur. J. Cancer, 29A. 1398, 1993. 9. Logothetis, C. J., Swanson, D. A., Dexeus. F., Chong, C., Ogden, S.. Ayala, A. G., von Eschenbach, A. C., Johnson, D. E. and Samuels, M. L.: Primary chemotherapy for clinical stage I1 nonseminomatous germ cell tumors of the testis: a follow-up of 50 patients. J. Clin. Oncol.. 5: 906, 1987. 10. Socinski. M. A., Garnick. M. B., Stomper, P. C., Fung. C. Y. and Richie, J. P.: Stage I1 nonseminomatous germ cell tumors of the testis: an analysis of treatment options in patients with low volume retroperitoneal disease. J. Urol., 140: 1437, 1988. tutional study. J. Clk. Oncol.,-11: 598, 1993. 17. Horwich, A., Sleijfer, D., Fossa, S., Stenning, S., Cook, P., Sylvester, R. and Vermeijlen, K: A trial of carbplatin-based combination chemotherapy in good prognosis metastatic testicular non semi- noma. Proc. Amer. Soc. Clin. Oncol., 13 231, 1994. 18. Culine, S., Mahjoubi, M., Philippot, I. and Droz, J. P.: Treatment of good-risk disseminated non-seminomatous germ cell tu- mours: the less bleomycin, the more cisplatin? Letter to the Editor. Eur. J. Cancer, 127: 1715, 1991. EDITORIAL COMMENT The authors present their experience with primary chemotherapy in patients with clinical stage I nonseminomatous germ cell cancer (radiographic staging) who have elevated P-HCG or AFP levels (or markers not decreasing appropriately based on half-life). Two recent reports have shown that patients with elevated markers alone who are treated with retroperitoneal lymph node dissection generally tend ultimately to require chemotherapy afterwards (references 2 and 3 in article). Whether these patients with persistent marker elevation alone can be stratified into high and low risk groups for requiring chemotherapy after retroperitoneal lymph node dissection is not addressed in the aforementioned 2 reports. The data in this article confirm what medical oncologists have known for some time, that is patients with elevated markers alone are in a good risk category and have an extremely high chance of being cured with cisplatin-based chemotherapy (reference 14 in article). Therefore, accu- mulating data would suggest that patients with no evidence of radio- graphic disease aRer orchiectomy but with elevated markers or mark- ers not decreasing appropriately based on half-life are most appropriately treated with cisplatin-based chemotherapy. A distinction should be made between the presented group and the general group of patients in whom documented retroperitoneal dis- ease is resected at retroperitoneal lymph node dissection. These pathological stage I1 cancers are cured by retroperitoneal lymph node dissection alone 50 to 75% of the time, depending on the volume of disease resected.' Richard S. Foster Department of Urology Un i Lwsi ty Hospital Inciianapolis. Indiana 1. Donohue, <J. P., Thornhill, J. A.. Foster, R. S., Bihrle, R., Rowland. R. G. and Einhorn. L. H.: The role ofretroperitoneal lymphadcnectomy in clinical stage B testis cancer: the Indiana University experience (1965 to 1989). J. Urol., 153: 85. 1995.
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Transcript of EDITORIAL COMMENT
1298 CHEMOTHERAPY IN EARLY STAGE TESTICULAR CANCER
combination. Four cycles provided results equivalent to those obtained with 3 cycles.14 The subsequent trial of patients treated with 3 cycles of EP with or without bleomycin demon- strated a sigmficant increase in the number of treatment fail- ures on the EP m . 1 5 Another theoretical approach to achieve a substantial decrease in the toxicity of chemotherapy is the use of carboplatin instead of cisplatin. However, 2 randomized stud- ies demonstrated inferior results with carboplatin compared to cisplatin.I6, 17 Consequently, omitting bleomycin in patients re- ceiving 4 cycles of EP and limiting the cumulative dose of bleomycin to 3 cycles of BEP represent 2 equivalent optimal alternatives for patients who receive primary chemotherapy for biological disease.1s I t is noteworthy that the 2 patients with active relapse had been primarily treated with either the VAB-6 or EC regimen and, therefore, they had not received optimal chemotherapy.
CONCLUSIONS
Primary chemotherapy yields excellent long-term results in patients with elevated serum tumor markers only after orchi- ectomy. Since results with primary retroperitoneal lymph node dissection suggest that elevated serum tumor markers usually reflect systemic metastases rather than retroperitoneal disease, primary chemotherapy using optimal regimens seems to be the most appropriate strategy to consider.
REFERENCES
11. Bosl, G. J., Geller, N. L. and Bajorin, D.: Serum tumor markers and patient allocation to good-risk and poor-risk clinical trials in patients with germ cell tumors. Cancer, 67: 1299, 1991.
12. Mead, G. M.: International consensus prognostic classification for metastatic germ cell tumours treated with platinum based chemotherapy: final report of the International Germ Cell Cancer Collaborative Group. Proc. Amer. SOC. Clin. Oncol., 14: 235, abstract 615, 1995.
13. Bosl, G. J.. Geller. N. L., Bajorin. D., Leitner, S. P., Yagoda, A., Golbey, R. B., Scher, H.. Vogelzang, N. J.. Auman. J.. Carey, R., Fair, W. R., Herr, H.. Morse, M., Sogani, P. and Whitmore, W.: A randomized trial of etoposide + cisplatin versus vinblas- tine + bleomycin + cisplatin + cyclophosphamide + dactino- mycin in patients with good-prognosis germ cell tumors. J. Clin. Oncol., 6: 1231, 1988.
14. Einhorn, L. H., Williams, S. D., Loehrer, P. J., Bircer, R., Drasga, R., Omura. G. and Greco, F. A.: Evaluation of optimal duration of chemotherapy in favorable-prognosis disseminated germ cell tumors: a Southeastern Cancer Study Group protocol. J. Clin. Oncol., 7: 387. 1989.
15. Loehrer, P. J., Johnson, D. H.. Elson, P.. Einhorn. L. H. and Trump, D.: Importance of bleomycin in favorable-prognosis disseminated germ cell tumors: an Eastern Cooperative On- cology Group trial. J. Clin. Oncol., 13: 470, 1995.
16. Bajorin, D. F., Sarosdy, M. F., Pfister, D. G., Mazumdar, M., Motzer, R. J., Scher, H. I., Geller, N. L., Faur, W. R., Herr, H., Sogani, P., Sheinfeld, J., Russo, P., Vlamis, V., Carey, R., Vogelzang, N. J., Crawford, E. D. and Bosl, G. J. : Randomized trial of etoposide and cisplatin versus etoposide and carbopla- tin in uatients with eood-risk germ cell tumors: a multiinsti-
1. Einhorn, L. H.: Treatment of testicular cancer: a new and im- proved model. J. Clin. Oncol., 8 1777, 1990.
2. Davis, B. E., Herr, H. W., Fair, W. R. and Bosl, G. J.: The management of patients with nonseminomatous germ cell tu- mors of the testis with serologic disease only after orchiec- tomy. J . Urol., 152: 111, 1994.
3. Saxman, S. B., Nichols, C. R., Foster, R. S., Messemer, J. E., Donohue, J. P. and Einhorn, L. H.: The management of pa- tients with clinical stage A testicular nonseminomatous germ cell tumors and persistently elevated serologic markers. Proc. Amer. Soc. Clin. Oncol., 14: 230, 1995.
4. Droz, J . P., Kramar, A., Ghosn, M., Piot, G., Rey, A, Theodore, C., Wibault, P.. Court, B. H., Pemn, J. L., Travagli, J . P., Bellet, D., Caillaud, J. M., Pico, J . L. and Hayat, M.: Prognostic factors in advanced nonseminomatous testicular cancer. A multivariate logistic regression analysis. Cancer, 62: 564, 1988.
5. Ghosn, M., Droz, J. P., Theodore, C., Pico, J. L., Baume, D., Spielmann, M., Ostronoff, M., Moran, A., Salloum, E., Kramar, A. and Hayat, M.: Salvage chemotherapy in refractory germ cell tumor with etoposide (VP-16) plus ifosfamide plus high- dose cisplatin. A VIhP regimen. Cancer, 63: 24, 1988.
6. Droz, J. P., Pico, J . L., Ghosn, M., Gouyette, A., Baume, D., Piot, G., Ostronoff, M., Theodore, C., Beaujean, F. and Hayat, M.: Long-term survivors after salvage high dose chemotherapy with bone marrow rescue in refractory germ cell cancer. Eur. J. Cancer, 27: 831, 1991.
7. Einhorn, L. H., Weathers, T., Loehrer, P. and Nichols, C.: Second line chemotherapy with vinblastine, ifosfamide, and cisplatin after initial chemotherapy with cisplatin, VP-16, and bleomy- cin in disseminated germ cell tumors. Proc. Amer. SOC. Clin. Oncol.. 11: 196, abstract 599, 1992.
8. Ibrahim, A,, Zambon, E., Bourhis, J. H., Ostronoff, M., Beaujean, F., Viens, P., Lhomme, C., Chazard, M., Maraninchi, D., Hayat, M., Droz, J. P. and Pico, J . L.: High-dose chemotherapy with etoposide, cyclophosphamide and escalating dose of car- boplatin followed by autologous bone marrow transplantation in cancer patients. A pilot study. Eur. J. Cancer, 29A. 1398, 1993.
9. Logothetis, C. J., Swanson, D. A., Dexeus. F., Chong, C., Ogden, S.. Ayala, A. G., von Eschenbach, A. C., Johnson, D. E. and Samuels, M. L.: Primary chemotherapy for clinical stage I1 nonseminomatous germ cell tumors of the testis: a follow-up of 50 patients. J. Clin. Oncol.. 5: 906, 1987.
10. Socinski. M. A., Garnick. M. B., Stomper, P. C., Fung. C. Y. and Richie, J . P.: Stage I1 nonseminomatous germ cell tumors of the testis: an analysis of treatment options in patients with low volume retroperitoneal disease. J. Urol., 140: 1437, 1988.
tutional study. J. C lk . Oncol.,-11: 598, 1993. 17. Horwich, A., Sleijfer, D., Fossa, S., Stenning, S., Cook, P., Sylvester,
R. and Vermeijlen, K: A trial of carbplatin-based combination chemotherapy in good prognosis metastatic testicular non semi- noma. Proc. Amer. Soc. Clin. Oncol., 1 3 231, 1994.
18. Culine, S., Mahjoubi, M., Philippot, I. and Droz, J. P.: Treatment of good-risk disseminated non-seminomatous germ cell tu- mours: the less bleomycin, the more cisplatin? Letter to the Editor. Eur. J. Cancer, 127: 1715, 1991.
EDITORIAL COMMENT
The authors present their experience with primary chemotherapy in patients with clinical stage I nonseminomatous germ cell cancer (radiographic staging) who have elevated P-HCG or AFP levels (or markers not decreasing appropriately based on half-life). Two recent reports have shown that patients with elevated markers alone who are treated with retroperitoneal lymph node dissection generally tend ultimately to require chemotherapy afterwards (references 2 and 3 in article). Whether these patients with persistent marker elevation alone can be stratified into high and low risk groups for requiring chemotherapy after retroperitoneal lymph node dissection is not addressed in the aforementioned 2 reports.
The data in this article confirm what medical oncologists have known for some time, that is patients with elevated markers alone are in a good risk category and have an extremely high chance of being cured with cisplatin-based chemotherapy (reference 14 in article). Therefore, accu- mulating data would suggest that patients with no evidence of radio- graphic disease aRer orchiectomy but with elevated markers or mark- ers not decreasing appropriately based on half-life are most appropriately treated with cisplatin-based chemotherapy.
A distinction should be made between the presented group and the general group of patients in whom documented retroperitoneal dis- ease is resected at retroperitoneal lymph node dissection. These pathological stage I1 cancers are cured by retroperitoneal lymph node dissection alone 50 to 75% of the time, depending on the volume of disease resected.'
Richard S. Foster Department of Urology U n i Lwsi ty Hospital Inciianapolis. Indiana
1. Donohue, <J. P., Thornhill, J. A.. Foster, R. S., Bihrle, R., Rowland. R. G . and Einhorn. L. H.: The role ofretroperitoneal lymphadcnectomy in clinical stage B testis cancer: the Indiana University experience (1965 to 1989). J. Urol., 153: 85. 1995.
