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CORRESPONDENCE .26). Although the preclinical data that we cite is also reassuring in this regard, the selectivity of DDTC protection should be tested in larger phase III clinical trials in reponsive tumor types. Finally, Cvitkovic et al should keep in mind that ours was a phase I trial. His title "DDTC ... or Just Water?" appropriately highlights the point that protectors should withstand the rigor of phase III testing. Charlotte Jacobs Branimir I. Sikic Stanford University School of Medicine Stanford,CA
Testis Cancer:A Model for Other Solid Tumors? To the Editor. The November issue of the Journal of Clinical Oncology contains a summary of the Karnofsky Lecture delivered by Dr Lawrence Einhorn at the 1990 American Society of Clinical Oncology meeting.' There is no question that his brilliant work with testicular cancer has contributed significantly to radically changing its prognosis. But is testis cancer really a relevant model for the development of therapeutic approaches for other solid tumors? Germ cells are in a different class than other cells. In the first place, they divide through a process of miosis as opposed to somatic cells, which divide through a process of mitosis. In the second place, germ cells are perhaps more "heavily programmed" than any other cell to undergo differentiation and maturation, and perhaps their malignant counterparts preserve these tendencies. It is still fascinating to find residual tumor masses that have changed from malignant to benign teratomas after a few courses of chemotherapy, something rarely, if ever, seen in any other adult malignancy. Does chemotherapy work in these cases by blindly and bluntly killing cells or by a more subtle mechanism, forcing differentiation? Based on these considerations, I wonder if germ cell malignancies can be taken as the model for therapy of other cancers, or if they should be considered exceptional tumors, with little relevance for the vast majority of cancers that are of somatic origin. Perhaps the therapeutic results achieved in testicular cancer cannot be duplicated because of the radically different biologic nature of germ cells and somatic cells. Perhaps the spectacular successes achieved in testicular cancer are misleading us into believing that these successes could be duplicated in other malignancies if only the right drug were to come along. It may be that the efforts to find the next "testicular cancer" are really delaying the recognition that the successful therapy of solid tumors will not depend on new cytotoxic drugs, but on a much better understanding of the biology of cancer and on the develop-
ment of rational ways to control cell growth, invasion, and metastasis. Martin S. Blumenreich Universityof Louisville School of Medicine Louisville, KY REFERENCE 1. Einhorn LH: Treatment of testicular cancer: A new and improved model. J Clin Oncol 8:1777-1781, 1990
Reply To the Editor. I appreciate the kind and thoughtful comments of Dr Blumenreich. There is no question that testicular cancer is a unique solid tumor and has marked chemosensitivity. This was even true before the era of cisplatin combination chemotherapy as in the 1960s and early 1970s, when it represented one of the few malignancies that was curable with chemotherapy, albeit only rarely in the dactinomycin era. I would like to stress, however, that the idea of using testicular cancer as a "model for a curable neoplasm" does not imply that common malignancies like lung cancer, breast cancer, pancreatic cancer, etc, can routinely be cured once we find the right drug in combination chemotherapy regimen to be used. Instead, I think it is appropriate to look at a curable, rather than incurable, solid tumor and try to investigate the successful strategy and use a similar philosophy and therapeutic management on other neoplasms as well. The seven separate points that I made in the summary of my Lecture are not unique to testicular cancer but, I feel, are applicable 1 to many more common solid tumors as well. Whether we will ever see an experimental drug such as cisplatin have the same degree of activity and subsequently revolutionize the cure rate in other solid tumors is obviously conjectural; nevertheless, I feel it still is a strong impetus for continuing to look at new drugs and a new treatment strategy. By no means does this lessen the importance of continued basic science research in elucidating the important pathways of metastasis and the basic molecular biology of individual cancers. Lawrence H. Einhorn University of IlndianaMedical Center Indianapolis,IN REFERENCE 1. Einhorn LH: Treatment of testicular cancer: A new and improved model. J Clin Oncol 8:1777-1781, 1990
Downloaded from ascopubs.org by UNIVERSITY of OTAGO on April 20, 2019 from 139.080.135.089 Copyright © 2019 American Society of Clinical Oncology. All rights reserved.
CORRESPONDENCE .26). Although the preclinical data that we cite is also reassuring in this regard, the selectivity of DDTC protection should be tested in larger phase III clinical trials in reponsive tumor types. Finally, Cvitkovic et al should keep in mind that ours was a phase I trial. His title "DDTC ... or Just Water?" appropriately highlights the point that protectors should withstand the rigor of phase III testing. Charlotte Jacobs Branimir I. Sikic Stanford University School of Medicine Stanford,CA
Testis Cancer:A Model for Other Solid Tumors? To the Editor. The November issue of the Journal of Clinical Oncology contains a summary of the Karnofsky Lecture delivered by Dr Lawrence Einhorn at the 1990 American Society of Clinical Oncology meeting.' There is no question that his brilliant work with testicular cancer has contributed significantly to radically changing its prognosis. But is testis cancer really a relevant model for the development of therapeutic approaches for other solid tumors? Germ cells are in a different class than other cells. In the first place, they divide through a process of miosis as opposed to somatic cells, which divide through a process of mitosis. In the second place, germ cells are perhaps more "heavily programmed" than any other cell to undergo differentiation and maturation, and perhaps their malignant counterparts preserve these tendencies. It is still fascinating to find residual tumor masses that have changed from malignant to benign teratomas after a few courses of chemotherapy, something rarely, if ever, seen in any other adult malignancy. Does chemotherapy work in these cases by blindly and bluntly killing cells or by a more subtle mechanism, forcing differentiation? Based on these considerations, I wonder if germ cell malignancies can be taken as the model for therapy of other cancers, or if they should be considered exceptional tumors, with little relevance for the vast majority of cancers that are of somatic origin. Perhaps the therapeutic results achieved in testicular cancer cannot be duplicated because of the radically different biologic nature of germ cells and somatic cells. Perhaps the spectacular successes achieved in testicular cancer are misleading us into believing that these successes could be duplicated in other malignancies if only the right drug were to come along. It may be that the efforts to find the next "testicular cancer" are really delaying the recognition that the successful therapy of solid tumors will not depend on new cytotoxic drugs, but on a much better understanding of the biology of cancer and on the develop-
ment of rational ways to control cell growth, invasion, and metastasis. Martin S. Blumenreich Universityof Louisville School of Medicine Louisville, KY REFERENCE 1. Einhorn LH: Treatment of testicular cancer: A new and improved model. J Clin Oncol 8:1777-1781, 1990
Reply To the Editor. I appreciate the kind and thoughtful comments of Dr Blumenreich. There is no question that testicular cancer is a unique solid tumor and has marked chemosensitivity. This was even true before the era of cisplatin combination chemotherapy as in the 1960s and early 1970s, when it represented one of the few malignancies that was curable with chemotherapy, albeit only rarely in the dactinomycin era. I would like to stress, however, that the idea of using testicular cancer as a "model for a curable neoplasm" does not imply that common malignancies like lung cancer, breast cancer, pancreatic cancer, etc, can routinely be cured once we find the right drug in combination chemotherapy regimen to be used. Instead, I think it is appropriate to look at a curable, rather than incurable, solid tumor and try to investigate the successful strategy and use a similar philosophy and therapeutic management on other neoplasms as well. The seven separate points that I made in the summary of my Lecture are not unique to testicular cancer but, I feel, are applicable 1 to many more common solid tumors as well. Whether we will ever see an experimental drug such as cisplatin have the same degree of activity and subsequently revolutionize the cure rate in other solid tumors is obviously conjectural; nevertheless, I feel it still is a strong impetus for continuing to look at new drugs and a new treatment strategy. By no means does this lessen the importance of continued basic science research in elucidating the important pathways of metastasis and the basic molecular biology of individual cancers. Lawrence H. Einhorn University of IlndianaMedical Center Indianapolis,IN REFERENCE 1. Einhorn LH: Treatment of testicular cancer: A new and improved model. J Clin Oncol 8:1777-1781, 1990
Downloaded from ascopubs.org by UNIVERSITY of OTAGO on April 20, 2019 from 139.080.135.089 Copyright © 2019 American Society of Clinical Oncology. All rights reserved.
