Mr. FLOOD. How long has that condition been in the lung? Dr. JAFFEE. It is probably there at the time of presentation, which is about 2 to 3 months, but it is microscopic and it is not detectable at the presentation. Mr. FLOOD. Is that condition peculiar alone to this disease? Dr. JAFFEE. It is present in some cancer, peculiar to this disease. Mr. FLOOD. Why can you not determine it exists by examining the lung? Dr. JAFFEE. Unfortunately, the tumor has to grow to a particular size before it can be diagnosed. Mr. FLOOD. How long does that take? Dr. JAFFEE. That probably takes 4 or 5 months. Mr. FLOOD. Even so, should you not find it then? Dr. JAFFEE. By the time the patient presents himself, the patient deserves immediate treatment. There is no sense in delaying it because approximately 20 percent of patients do not have the submicroscopic evidence of disease in the lungs and they require immediate amputation for cure. I will try to illustrate that as I proceed. Mr. FLOOD. Of course, general checkups do not include that kind of examination. Dr. JAFFEE. That is correct, sir. Now, as I indicated, the patient on the left-hand side of the chart that I have submitted has a tumor in the leg. Since the metastases are not visible under radiological examination, an immediate amputation is performed. Death, however, occurs within 18 months because these metastases eventually appear. This is noted in the upper section of the chart. Only approximately 15 or possibly 20 percent of patients will be cured because at the time of the presentation Mr. FLOOD. Off the record. [Discussion off the record.] Mr. FLOOD. Back on the record. In some cases I understand the lung condition does not exist indentically with the carcinoma, is that so? It does not always exist? Dr. JAFFEE. That is correct in 20 percent of patients; in the optimum circumstances it may not be there. I tried to illustrate in the lower section of the chart, indicating that approximately 15 percent of patients will be cured because at the time of presentation the metastases, the tumor has not developed in the lungs. Under those circumstances an immediate amputation will result in a cure, nothwithstanding 80 percent of the patients still die because submicroscopic disease has spread to the lungs at the time of the presentation. Mr. FLOOD. But the condition that exists in the lung is so well-known that the minute there is any suggestion of carcinoma of this kind, the lung is always examined? Dr. JAFFEE. That is correct, sir, that is correct. Now, research in a group of 20 patients treated in a new way by means of chemotherapy since 1972 indicates that this group will experience a 70-percent survival instead of a 20-percent survival as in the past. On patient who was treated prior to the initiation of this formal study in the 20 patients has remained free of tumor for 4 years and seems to have many more years ahead of her. This is illustrated in the second chart that I have submitted. The chart shows that in the left radiograph there are two lung metastases which developed after amputation. Two months later, following chemotherapy, eradication of these metastases has been achieved. The patient is presently alive and well, free of disease and has demonstrated no adverse effects whatsoever to the chemotherapy administered. Now, this is not a fluke. I do not speak just for myself and for my work. We are putting data together from five major centers in the country, comprehensive centers with all the personnel and resources to standardize procedures rigidly. I see no scientific or mathematical reason why the improved survival rate will not be the survival rate in bone cancer cases in the near future. Mr. FLOOD. Would you say it would apply to the male and female equally? Dr. JAFFEE. There is a slight preponderance in the male. Mr. FLOOD. Any age bracket? Dr. JAFFEE. From 10 years to 25 years, approximately. Under the circumstances of the condition of the treatment that we have administered, sir, I would submit that in the near future the 20-percent survival rate will be history. Now my work involves the use of drugs to counteract the growth of these small tumors in the lung which most often accompany the bone cancer at the time of presentation. The drugs comprise methotrexate in high doses with citrovorum factor to counteract the effects of the methothrexate and adriamycin. Your investment of the taxpayers' money is characterized in one of my recent articles which appeared in the February issue of this current year in Pediatric Annals designed specifically for dissemination to the general practitioner and to the pediatrician. I quote: Many of the protocols are of an investigational nature and can be administered only in specialized cancer centers where adequate supportive measures are available. However, the resources and cooperation of the referring physician are usually enlisted to help in observing the patient in the intervals between treatments or to assist in the administration of the chemotherapeutic agents on an ambulatory basis. You see, sir, we cannot get along without the comprehensive cancer centers, but in similar fashion we must keep the family doctor actively involved. I chose my words carefully, then, and I choose them carefully now when I quote again from this article: The preliminary results obtained with chemotherapy are highly encouraging and suggest that the natural history of the bone tumor osteogenic sarcoma has been altered. This will not change the face of this so-called dread disease. This new treatment will be required by only some 700 of the 365,000 cancer cases per year in the United States. But for those 700, their families, their friends, their emplovers, this advance is truly meaningful. It provides hope for all and life extension for many. The hope is important because it convinces both the patient and the doctor to eke out every chance of support for a cure. While fewer than two cancer patients per thousand have bone cancer, this same sort of advance is being made by concentrated drug research on breast cancer, prostate, bladder, colon, lung and others. These are the solid tumors, the big ones, the difficult ones. The small bits of progress definitely add up. The national cancer plan is not 5 years old yet. If we had found a 100-percent sure cure, the instant that you enacted the conquest of cancer law, we would still not have a single 5-year survivor for the statisticians. I am convinced that we shall have significant increases in five-year survival rates as a result of intense studies of known drugs and other therapies as we pull more and more science out of the fundamental research laboratories and the academic journals to be used for the work of the patient. We cannot do this without adequate funding. Please give cancer patients the $898.5 million in the citizens budget. It is less than the panel of consultants recommended. Anything below this total reneges on the country's decision to make the conquest of cancer a national priority. Mr. FLOOD. I notice some drugs coming from Great Britain, and I also note your accent. I think particularly of the drug on gallstones. Where was the drug you are talking about discovered? Dr. JAFFEE. I am talking about drugs which are specifically active in cancer. Mr. FLOOD. I know. Where was it discovered, the first one you talked about? Dr. JAFFEE. This was discovered in our own country, sir, the United States. Mr. FLOOD. Thank you very much. Dr. JAFFEE. Thank you. [The witness' full statement and exhibit follow:] ADVANCES IN THE TREATMENT OF OSTEOGENIC SARCOMA Mr. Chairman and members of the subcommittee, I am Dr. Norman Jaffe, a physician at the Sidney Farber Cancer Center, located in Boston, Mass. The institution was previously known as the Children's Cancer Research Foundation and was established over 25 years ago by Dr. Sidney Farber for the treatment of cancer in children. The center subsequently broadened its activities and assumed major responsibilities for the treatment of cancer in adults. It is affiliated with Harvard Medical School. I have been engaged in full time cancer research for the past 10 years, most of which I spent under the direction of Dr. Sidney Farber and, more recently, under the current director and physician-in-chief of the center, Dr. Emil Frei III. I appreciate the opportunity to report to you on our investigations in the treatment of one of the more common bone tumors, previously considered unresponsive to chemotherapy. OSTEOGENIC SARCOMA This is a bone tumor which occurs primarily in preteenage and teenage children. The underlying mechanisms responsible for its occurrence and development are unknown, although occasional cases are probably related to the prior administration of radiation therapy to the affected area. In older patients, the condition is usually found in association with Paget's disease of the bone. The tumor may arise in various parts of the skeleton. However, the predominant areas affected are the thigh, upper part of the leg and upper part of the arm near the shoulder. NATURAL COURSE OF THE DISEASE In the majority of patients, the tumor presents initially as a vague dull ache in the limb. This may be accompanied by a minor swelling. In over 80 percent of such patients, microscopic deposits of tumor have spread to the lungs at the time of diagnosis. This is referred to as pulmonary metastases. These metastases are not visible by routine radiographic examination. However, they account for the poor survival rate which has been obtained with conventional treatment involving immediate amputation. The metastases enlarge and can be detected within 6 to 9 months by radiologic examination of the lungs. Accelerated growth generally occurs at this stage and most patients die within 12 months after the chest radiograph becomes positive. The survival rate in optimum circumstances is approximately 20 percent. CHEMOTHERAPEUTIC ADVANCES During the past 4 years, several chemotherapeutic agents have been shown to be effective in the management of osteogenic sarcoma. These principally comprise high-dose methotrexate followed by citrovorum factor and adriamycin. (1) High-dose methotrexate and citrovorum factor In 1971, the Sidney Farber Cancer Center demonstrated that high-dose methotrexate followed by citrovorum factor (so-called citrovorum factor rescue) was effective in producing destruction of tumor in a number of patients with osteogenic sarcoma which had spread to the lungs. The procedure involves the administration of massive potentially toxic doses of methotrexate over several hours followed by citrovorum factor which counteracts the toxic effects of the drug. In the early investigations, this chemotherapeutic regimen produced a 40 percent response rate. One of the patients who responded has remained free of tumor for the past 4 years and has not demonstrated any adverse effects from the chemotherapeutic program. Investigations at the clinical and experimental level demonstrate that chemotherapy is far more effective against microscopic disease than it is against gross or bulk tumor. This observation provided the impetus to administer high-dose methotrexate-citrovorum factor treatment to newly diagnosed patients without evidence of clinical spread to the lungs. It was considered that the potential for achieving tumor destruction would be far greater if the effective chemotherapeutic regimen were employed early when possibly only microscopic spread of the disease had occurred. Consequently, 20 consecutive patients, most of whom underwent immediate amputation, were subjected to treatment over the succeeding 2 years. Results.-The survival of these patients has been markedly improved. With followup periods ranging from 1% to 31⁄2 years, 70 percent remain free of disease in comparison to past experience where the survival rate was approximately only 20 percent. Projections based on data pooled from five major centers in the United States employing similar programs would suggest that this survival rate will not change and, under these circumstances, a permanent increase in the cure rate is anticipated. (2) Adriamycin In addition to high-dose methotrexate with citrovorum factor rescue, adriamycin has also been shown to be effective in osteogenic sarcoma. Consequently, a new treatment program combining both effective regimens was initiated at the Sidney Farber Cancer Center in April 1974. Although the results of this program are still preliminary, projections based on data to date would indicate that an even greater disease-free survival may be anticipated. CAN AMPUTATION BE AVOIDED? The encouraging results obtained with the combination of high-dose methotrexate and citrovorum factor and adriamycin prompted investigations at the Sidney Farber Cancer Center and elsewhere to determine the feasibility of performing local resection in selected cases rather than classical amputation for removal of the primary tumor. Preliminary results indicate that preservation of the limb with useful function together with cure under these circumstances may, indeed, be possible. Additional major studies in this direction are in progress. PROJECTIONS FOR THE FUTURE Experiences in osteogenic sarcoma have firmly demonstrated that chemotherapy is far more effective against microscopic disease. The results are supported by recent reports that adjuvant chemotherapy employed in patients with stage II breast cancer immediately following surgery significantly decreased the recurrence rate with followup periods of up to 2 years. These exciting results strengthen the need for the early administration of chemotherapy. Projections based on these experiences herald an increase in the number who may be cured. They call for intensified support on a nationwide basis for programs designed to improve the clinical management ultimately leading to major advances in the conquest of this disease. DIABETES HON. H. JOHN HEINZ III, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF PENNSYLVANIA CARL STENZLER, ACTING CHAIRMAN, PENNSYLVANIA DIABETES INSTITUTE DR. ARNALL PATZ, PROFESSOR OF OPHTHALMOLOGY, DIRECTOR OF DR. RICHARD A. FIELD, PHYSICIAN IN CHIEF, NEW ENGLAND DR. ROBERT KUGEL, VICE PRESIDENT FOR HEALTH SCIENCES, UNIVERSITY OF NEW MEXICO DR. WILLIAM HUTTON, EXECUTIVE DIRECTOR, NATIONAL COUNCIL OF SENIOR CITIZENS Mr. FLOOD. I see our distinguished colleague from the great Commonwealth of Pennsylvania, Congressman Heinz. Mr. HEINZ. Mr. Chairman, thank you very much. Mr. Chairman, I have no prepared statement; my remarks will be brief. |