Progress against cancer should be measured by several criteria: increased knowledge of the fundamental nature of malignant disease; identification and control of factors involved in cause and prevention; improvements in detection, diagnosis, and treatment leading to increased survival for the patient. The ultimate criterion, of course, is the control of cancer in man; and judged by this, treatment with drugs continued to provide encouraging evidence of progress during the past year.
Complete remissions of disease for extended periods have been induced with drugs in patients with widespread, rapidly progressive cancers, such as acute leukemia, Hodgkin's disease, childhood solid tumors, and a few other types. Some of these results are being produced by intermittent administration of combinations of drugs in high doses according to carefully planned schedules based on results of extensive laboratory studies of growth characteristics of cells. Such studies have shown that destructive effects of drugs against cancer cells can be increased without serious additional harm to normal cells. Intense exploration of the best methods of prolonging remissions in such patients is in progress. At the same time research is under way to extend the principles learned with these types of cancer to the more slowly growing tumors, such as those of the lung, breast, and colon-rectum, which make up the bulk of the cancers that afflict man.
Recent analysis of studies initiated only a few years ago substantiates the remarkable pace of advancements in cancer chemotherapy.
In 1968, at major treatment centers, it has been possible to restore 90 percent of patients with acute lymphocytic leukemia—the most common form of the disease in children—to complete, though temporary, good health; and most of these patients may be expected to live at least three years. As recently as four years ago the complete remission rate was 50 percent and the median length of survival only 12 to 19 months.
Drug treatments, coordinated with supportive therapy to overcome problems of hemorrhage and infection, are yielding high remission rates and increased median length of survival in children with acute lymphocytic leukemia.
Another encouraging development is the increasing number of persons surviving more than five years after diagnosis of leukemia. The Acute Leukemia Task Force, a group of medical experts assembled by the National Cancer Institute to aid in developing a coordinated research effort in this field, has compiled a registry of more than 150 long-term survivors. This was done by sending questionnaires to blood specialists all over the world. From the returns, Task Force members have reported that a discontinuance of leukemia therapy appears justifiable and perhaps advisable seven years from diagnosis, if a patient has had no evidence of disease for at least four years. This strongly suggests the possibility that, in some cases, leukemia can be considered "cured."
Besides the drugs themselves, the technique of administering them in combinations intermittently is given major credit for recent successes in treatment. Four agents most often used have been prednisone, vincristine, mer-captopurine, and methotrexate, but other drugs are also effective and new ones may provide even better treatment combinations in the future.
One drug found increasingly useful during the past year was cytosine arabinoside. This agent is helpful in treating acute lymphocytic leukemia which has become resistant to other drugs, and is also effective against undifferentiated childhood leukemia and the acute myelocytic form of the disease. In one study, National Cancer Institute investigators reported that of 34 patients with acute myelocytic leukemia receiving relatively high doses of cytosine arabinoside, 18 achieved complete remissions during which all evidence of their disease disappeared.
Encouraged by successes in treating leukemia with combinations of drugs, physicians have been applying this therapeutic technique to other capcers. Early, or localized, Hodgkin's disease yields to intensive irradiation, but for far-advanced disease a regimen of 4-drug treatment has been found most effective. Thus, adequate radiation therapy and adequate drug therapy provide opportunities for dramatically increasing the long-term survival rate for Hodgkin's disease, considered tantamount to cure.
Concurrent use of two anticancer agents, dactinomycin and vincristine sulfate, has produced regressions of solid tumors of childhood without serious side effects, always a problem in cancer chemotherapy. Investigators administered the two drugs to 18 children, ranging from 8 months to 16 years of age, with 9 types of inoperable malignant tumors. All patients improved and in some of the children response to chemotherapy was such that subsequently the tumors could be removed by surgery or destroyed by radiation therapy.
A drug, melphalan, has been found to produce good response and prolong survival' in a high percentage of patients with multiple myeloma, cancer of the plasma cells, present in bone marrow. In addition, National Cancer Institute and other investigators have reported that the calcium loss characteristic of this form of cancer can be partially restored by fluoride treatment. Fluoride treatment has also been suggested for metastases (secondary growths of a primary tumor) to the bones of patients with such common tumors as those in the breast and prostate.
The well-recognized, dangers of drug treatment have been highlighted in a report by a group of Veterans' Administration investigators participating in the National Cancer Institute's cooperative chemotherapy program. These physicians found that, although estrogen therapy results in a slight reduction in deaths from cancer of the prostate, it substantially increases the risk of death from cardiovascular disease. In many cases, this risk is justified by the severity of malignant disease; in others, alternative forms of treatment may be indicated.