Albert Lasker
Clinical Medical Research Award

Award Description

Joseph Burchenal
Denis Burkitt
Paul Carbone
Vincent DeVita, Jr.
Isaac Djerassi
Emil Frei III
Emil Freireich
Roy Hertz
James Holland
Edmund Klein
Min Chiu Li
V. Anomah Ngu
Donald Pinkel
Eugene Van Scott
John Ziegler
C. Gordon Zubrod
 
Joseph Burchenal
For his outstanding contribution in recognizing the importance of Burkitt's tumor as a model.

In 1960, Dr. Burchenal visited East Africa to investigate the possibility of initiating a treatment program in liver cancer. During the trip he became aware of Burkitt's tumor and promptly recognized its potential importance therapeutically as a "stalking horse" for other types of neoplastic disease, particularly acute leukemia.

It was he who stimulated and guided the early chemotherapeutic trials of Burkitt's tumor and was thus responsible for the ultimate observation that long-term survivals free of disease were possible.

Dr. Burchenal has persistently emphasized the parallels between Burkitt's tumor and acute leukemia. His lifelong dedication to leukemia research has contributed substantially to the development of more effective therapies, and potential long-term survivals for patients with acute leukemia.
 
Denis Burkitt
For his outstanding contribution in first identifying Burkitt's tumor.

In 1957, Denis Burkitt, a British surgeon working in East Africa, was the first to recognize that tumors appearing in characteristic sites and often occurring in the same individuals, were really different manifestations of the same type of tumor.

The surgical treatment of the disease was highly unsatisfactory and no radiotherapy was available in East Africa.

In 1961, his early treatment with chemotherapy was remarkably successful and led to the elaboration of a number of chemotherapeutic programs for the treatment of the disease. Burkitt himself participated in the development of effective chemotherapy for this tumor until 1966.

It was his recognition and clear description of the tumor which led to its use as a model for the development of other chemotherapeutic regimens for Burkitt's tumor, and the extrapolation of information gained in those studies to other kinds of cancer.

Denis Burkitt's work also brought a stimulus to leukemia chemotherapy and to studies of host defense mechanisms in cancer, and to the possible causation of human cancer by viruses.
 
Paul Carbone
For his outstanding contribution to the concept of combination therapy in the treatment of Hodgkin's disease.

Dr. Carbone has developed a treatment for patients with Hodgkin's disease, a specialized form of cancer affecting the lymph nodes, spleen, liver, lungs and bone marrow, in various stages of its spread. Through the combined use of nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP), plus other forms of therapy—i.e., intermittent treatment to allow for host recovery, and prolonging the induction treatment for six months—Dr. Carbone has been successful in keeping 70 percent of the patients alive for five years or more; and 40 percent free of disease for five years. This treatment has been extended to over 250 patients at the National Cancer Institute, and several thousand around the world.

Without Dr. Carbone's application of combination therapy in Hodgkin's disease, most of the patients he treated would not ordinarily have lived more than two years after diagnosis. His accomplishment has given great impetus to the use of combination chemotherapy in all other forms of cancer.
 
Vincent DeVita, Jr.
For his outstanding contribution to the concept of combination therapy in the treatment of Hodgkin's disease.

Dr. DeVita defined the infectious complications associated with Hodgkin's disease, explored the cell cycle characteristics of human tumors which might affect their responsiveness to drugs, and expanded greatly the value of chemotherapy.

Out of a group of 100 patients with advanced Hodgkin's disease who had achieved remission by using vinca alkaloids, alkylating agents, prednisone and procarbazine, Dr. DeVita has been successful in keeping about 70 percent of them alive and free of disease after five and six years.

Furthermore, 41 percent out of those who were in complete remission have remained continuously free of disease—without treatment—for up to six years.

Dr. DeVita's major contribution has been the development of four-drug therapy for advanced Hodgkin's disease. His methods have brought about a prolongation of remission never before achieved.
 
Isaac Djerassi
For his outstanding contribution in the supportive care, by platelet transfusion, of patients receiving intensive chemotherapy.

Soon after the era of chemotherapy of cancer was inaugurated in 1947, two great needs were recognized: control of bleeding, and of infection secondary to thrombocytopenia and leukopenia, as part of bone marrow failure induced either by therapy or by replacement of the bone marrow by cancer.

To replace the blood elements lacking in leukemia and other cancer patients, supportive care was initiated whereby platelets and white cells were separated from the blood so they could be transfused separately.

Dr. Djerassi perfected and extended these techniques, and during the past 18 years has treated over 1000 patients with platelet transfusions. The availability of platelet transfusions made possible the use of intensive drug combination therapy and much larger doses of methotrexate. He obtained striking responses consistently with this approach, in patients with tumors previously considered unresponsive to folic acid antagonists, including resistant acute leukemia, lymphosarcoma, and primary lung cancer.

His latest achievement was the perfection of filtration-leukophoresis apparatus which has made white cell replacement comparable to that already achieved for platelets. Without this work the resultant great increase in the effectiveness of chemotherapy of cancer would not have been possible.
 
Emil Frei III
For his outstanding contribution in the application of the concept of combination chemotherapy to lymphoma and acute adult leukemia.

During the past 17 years, Dr. Frei has made important contributions to clinical cancer chemotherapy. These include the introduction of several new effective chemicals, and especially the development and use of combination of chemotherapy. He has been particularly responsible for rational development in cancer chemotherapy through clinical investigation, clinical pharmacologic, and cytokinetic approaches. In addition to the leadership in such investigations within the National Cancer Institute, Dr. Frei developed and led, as chairman, two major multi-institute cancer chemotherapy groups, which made possible far more rapid progress in chemotherapeutic trials in this country and in Europe.

The more effective use of established agents, and the introduction of new chemicals and combination chemotherapy in Dr. Frei's studies continued at the M.D. Anderson Hospital, have resulted in a marked increase in the remission rate, duration of remission and survival in acute leukemia in children and adults and in patients with disseminated Hodgkin's disease.

Thus, in children with acute leukemia, a 90 percent complete remission rate, a 36-month median duration at remission, and a 25 to 35 percent survival rate at five years has been achieved.

In disseminated Hodgkin's disease, an 80 percent complete remission rate has been achieved, and 40 percent of such patients are without evidence of cancer after four years.

More recently, progress by combination chemotherapy along the above lines is being achieved through Dr. Frei's efforts in patients with metastatic cancer of other types. These include response rates exceeding 50 percent in patients with breast cancer; 40 percent in patients with soft tissue sarcoma; and 20 percent in patients with malignant melanoma.

Dr. Frei's pioneering role in cancer chemotherapy is founded on his skill as a physician, his appreciation of the importance of basic research in clinical pharmacology, and his qualities of leadership.
 
Emil Freireich
For his outstanding contributions in combination chemotherapy, and in supportive care of patients receiving combination chemotherapy for acute leukemia.

At the National Cancer Institute, from 1955 to 1965, Dr. Freireich participated with Dr. Emil Frei III in the treatment of 477 acute leukemic children, with methods of combined chemotherapy. This multiple drug combination regimen, consisting of vincristine, methotrexate, mercaptopurine and prednisone (POMP), induced a 90 percent complete remission rate. Further development of such treatment has led to five-year survival rates of 30 percent in childhood lymphoblastic leukemia, in studies from 1962 to the present.

In adult leukemia, in studies with Dr. Frei at M.D. Anderson Hospital from 1965 to the present, Dr. Freireich has participated in the treatment, with combination therapy, of 300 men and women with acute leukemia. For these patients, a program of Cytoxan, oncovan, arabinoside, and prednisone (COAP) was developed. As a result, in the most recent studies, about 50 percent of such adult patients achieved complete remission, with average duration of remission of one year. The overall prolongation of survival for patients who do respond is about a year; for 25 percent of such patients, life is prolonged two years.

In supportive care, Dr. Freireich provides a protective isolation of the patient from infectious agents in the environment, thus permitting more aggressive and intensive anti-leukemic therapy. In addition, he has been a pioneer in the development of the blood cell separator, which permits the use of platelet and white cell transfusions to patients whose own defenses are inadequate against infection or hemorrhaging.

Dr. Freireich's zeal and innovative skill in perfecting supportive therapy have made chemotherapy a much more effective treatment.
 
Roy Hertz
For his outstanding contribution to the successful chemotherapeutic treatment of gestational choriocarcinoma.

Dr. Hertz has treated large numbers of patients, in a study over a period of 20 years, for gestational choriocarcinoma, a highly malignant cancer which originates in tissue which is normally a constituent of the placenta.

Dr. Hertz and Dr. Min Chiu Li were the first to demonstrate a complete control, by drugs alone, of gestational choriocarcinoma, resulting in the high five-year cure rate of over 90 percent among those patients who were treated within the first four months of the onset of the disease, and of 70 percent among all of the patients whose disease had already metastasized. The drugs which brought about these results were methotrexate and actinomycin D, used either individually or sequentially.

Before Dr. Hertz's method of treatment with drugs, victims of choriocarcinoma had a survival time of only a few months to a year from the onset of the cancer. Now, as a result of the work of Dr. Hertz (and Dr. Li), 90 percent can be saved when treated soon enough. Furthermore, drug treatment has obviated the need of hysterectomies in most women afflicted with this cancer, and many women successfully treated have subsequently had normal pregnancies, impossible prior to the advent of drug therapy.

Seven regional centers, originally set up by Dr. Hertz in 1965 for the treatment of choriocarcinoma, remain in existence. They have consistently confirmed, in hundreds of cases over the past seven years, the findings of the original study, and continue to achieve successful cures.
 
James Holland
For his outstanding contribution to the concept and application of combination therapy in the treatment of acute leukemia in children.

Dr. Holland, as chairman of Acute Leukemia Group B—a cooperative, international group of physicians and scientists—has provided the outstanding leadership for the Group's investigations which has resulted in increasing the life expectancy of children with acute lymphocytic leukemia.

Since 1956, the Group has studied 1538 patients with this disease. In 1956, only 30 percent of children lived one year from the onset of their disease. Now, 90 percent do.

In 1956, only 4 percent lived four years from the start of their disease. Now, in 1972, more than 40 percent of such children live as long as four years.

In 1966, out of 267 children who started treatment then, 27 percent have survived five years.

In another group of 55 children treated in 1966, nine are still alive and well, without evidence of disease, four years or more after completion of the last drug treatment.

In one segment of a program started in 1968, 33 children were treated in a new regimen of combination therapy. Twenty-nine have survived since 1968, and the projected probable survival rate among them appears to be the most favorable in the Group's experience to date.

Dr. Holland's success in leadership is based upon his great clinical skill, and his outstanding ability in clinical investigation.
 
Edmund Klein
For his outstanding contribution in the treatment of premalignant and malignant cancers of the skin.

Dr. Klein pioneered the development of local chemotherapy of tumors of the skin as a new treatment modality in over 500 patients, with an aggregate of more than 15,000 neoplastic lesions, and observation periods in excess of five years. He adapted known general systemic anticancer chemicals for the eradication of premalignant and superficial malignant tumors of the skin, which resulted in a cure rate of up to 95 percent in these patients. He was responsible, therefore, for an important new therapeutic weapon, particularly for those skin cancers which were so situated that they could not be treated effectively by surgery or radiotherapy.

Through Dr. Klein's method of topical application, healing of the skin cancers usually occurs with no scarring, and normal tissue is left unharmed. This treatment has been successful even against some basal cell and squamous cell carcinomas.

Dr. Klein expanded his studies to demonstrate that immunologic factors could be manipulated to control malignant disease in animals and in man. His observations have pointed the way to the justification for great expansion of immunotherapy alone, or in combination with chemotherapy in the treatment of cancer.

Dr. Klein's pioneering and persistent efforts have extended, to an important degree, the therapeutic attack on cancer.
 
Min Chiu Li
For his outstanding contribution to the successful chemotherapeutic treatment of gestational choriocarcinoma.

Dr. Li (with Dr. Roy Hertz) in 1956 was the first to demonstrate the first chemical cure of gestational choriocarcinoma resulting from pregnancy, by use of a drug—methotrexate.

Choriocarcinoma may take two forms—gestational, originating in the tissue that would normally be a consitituent of the placenta, and non-gestational—i.e., that originating in the sexual glands of both sexes. Both types, when untreated, kill 90 percent of their victims.

Both types of tumors secrete a hormone that can be measured. Dr. Li and associates utilized techniques for so measuring secretion of hormone as an index of tumor response to methotrexate. This enabled them to detect whether or not the cure was complete.

As a result, in 1961, Dr. Li and associates were able to initiate an improvement in the earlier treatment of gestational choriocarcinoma by using actinomycin D against those cases which had resisted treatment by methotrexate alone. The two drugs, later used sequentially by Dr. Li and other investigators, resulted in a 75 to 85 percent, 5 to 10 year cure rate, out of 500 patients so treated during the last decade.

The contributions of Dr. Li thus stand as an important landmark in cancer chemotherapy.
 
V. Anomah Ngu
For his outstanding contribution to the expansion of the successful chemotherapeutic treatment of Burkitt's tumor.

Dr. Ngu, a professor of surgery formerly working in the University College Hospital, Ibadan, Nigeria, recognized the importance of the identification of Burkitt's tumor and its applicability to a similar group of patients being observed in West Africa.

In 1961, Dr. Ngu and his colleagues began to study the influence on Burkitt's tumor of various chemotherapeutic agents and treated more than 400 patients. The results were complete regression in over 90 percent of such patients. Over 40 percent in his series have survived five years, and some over ten years. Recurrences after two years are rare and are exceptional after three years in some series.

Before Dr. Ngu's programs, few patients with Burkitt's tumor survived five years. Since his success with Burkitt's tumor, chemotherapeutic cancer centers have been established in other parts of Africa, including small mission hospitals in Nigeria which have also been able to treat Burkitt's tumor successfully.
 
Donald Pinkel
For his outstanding contribution to advances in the concept of combination therapy in the treatment of acute leukemia in children.

In 1962, Dr. Pinkel and associates initiated at St. Jude a program of therapy of acute lymphocytic leukemia for the children at that hospital.

In the course of the decade from 1962 to the present, seven successive studies were designed, each an improvement over its predecessor, during which time a total of 346 children were treated for the disease.

Dr. Pinkel's method includes prolonged multiple drug treatment for two or three years, with prednisone and vincristine, to induce remission of the disease; and methotrexate, mercaptopurine, and Cytoxan, to continue subsequent disease-free survival. Cobalt radiation is administered to the head and spine early in remission, to prevent the development of central nervous system leukemia.

Dr. Pinkel has demonstrated that such treatment can be carried out with minimal and even no hospitalization, and can result in the prospect of long survival for a substantial proportion of the children.

Recent studies indicate that 50 to 55 percent out of 80 children treated at St. Jude from 1967 to 1970 by his method are in continuous complete remission.

These studies represent important progress in the treatment of children with acute leukemia.
 
Eugene Van Scott
For his outstanding contribution to the concept of topical chemotherapy in the treatment of mycosis fungoides.

Dr. Van Scott has demonstrated that topical chemotherapy can produce disease-free survivals, now extending beyond two years, in patients with mycosis fungoides—an especially virulent form of cancer beginning in the skin—when the disease is limited to the skin and treatment is begun prior to lymph node involvement.

In such cases, Dr. Van Scott has achieved regression of the disease in 37 patients—about 50 percent out of 76 treated during the past four years. Disease-free survival for a period beyond two years has now been realized in 13 patients out of the 37 who achieved remission. The remaining patients have not been on treatment sufficiently long to arrive at two-year remissions.

Early diagnosis and treatment by topical chemotherapy can prevent spread of mycosis fungoides from the skin to the lymph nodes. Once the disease has reached the lymph nodes, it is almost always fatal.

Dr. Van Scott has developed a treatment, when the disease is still limited to the skin, whereby he first desensitizes the patient, and then uses nitrogen mustard preparations applied topically to the patient's body daily or three days a week, until the disease has disappeared—sometimes for as long as two years.

Dr. Van Scott's work represents early evidence of an important improvement in the treatment of mycosis fungoides.
 
John Ziegler
For his outstanding contribution in increasing the cure rate of Burkitt's tumor by chemotherapy.

Dr. Ziegler, a senior investigator for the National Cancer Institute, has spent the last five years directing the Uganda Cancer Institute, Kampala, Uganda, Africa, leading the fight there against Burkitt's tumor, a cancer prevalent in Africa, which manifests itself especially in the jaw, eyes, ovaries, and kidneys of African children.

During this period, in a trial initiated by Dr. Ziegler, more than 200 patients with Burkitt's tumor were treated with Cytoxan intravenously, resulting in remission in 90 percent of cases after a single dose. Vincristine, methotrexate, cytosine arabinoside, and multiple doses of Cytoxan extended the remission for long periods.

Of those in remission, there is now a 67 percent five-year survival rate. Before the development of combination chemotherapy, essentially no patients survived five years.

In addition to chemotherapy, BCG immunotherapy is now being used to stimulate immunological responses against the tumor. Preliminary results are encouraging, and the trial is being continued.

Research into Burkitt's lymphoma has yielded important information applicable to the chemical and immunological treatment and control of other types of cancer as well.
 
Special Award to
C. Gordon Zubrod
For his leadership in expanding the frontiers of cancer chemotherapy.