Faculty Bibliography

4'-(9-Acridinylamino)methanesulfon-m-anisidide (m-AMSA; NSC-249992) is a new anticancer agent that has undergone extensive experimental investigation. Clinical trials have recently been initiated and current data suggest a wide spectrum of antitumor activity in human cancer.

This paper considers two-stage patient-accrual plans for phase II trials of anticancer drugs. The purpose is to identify the therapeutic level of drugs as either above or below a reference response rate. Using such a plan, decisions concerning the future disposition of drugs can be made more formally and objectively. The tables used to implement the plan are prepared for a 20% reference response rate, due to its wide acceptance in the design of phase II clinical trials.

Immune reactivity of patients with early or advanced breast cancer, compared with healthy controls, has been measured using in vivo and in vitro tests. The results of our study show that impairment of cellular responsiveness occurred in women with advanced disease.

We have conducted a phase II trial of cisdiammino-dichloro platinum (CDDP) which demonstrates its remarkable activity in testis embryonic carcinoma, in ovary carcinoma and in epidermoid cancers, especially head and neck and uterus cervix carcinoma. Its toxicity in mainly digestive and renal. This compound is now indicated in combinations in the case of the above mentioned tumors.

Potential risk factors responsible for development of doxorubicin-induced congestive heart failure were examined through retrospective analysis of 4018 patient records. The overall incidence of drug-induced congestive heart failure was 2.2% (88 cases). The probability of incurring doxorubicin-induced congestive heart failure was related to the total dose of doxorubicin administered. There was a continuum of increasing risk as the cumulative amount of administered drug increased. A weekly dose schedule of doxorubicin was associated with a significantly lower incidence of congestive heart failure than was the usually employed every 3-week schedule. An increase in drug-related congestive heart failure was also seen with advancing patient age. Performance status, sex, race, and tumor type were not risk factors. These data will enable clinicians to better estimate the risk/benefit ratio in individual patients receiving prolonged administration of doxorubicin. They also provide a basis for the investigation of less cardiotoxic anthracycline analogues or for designing measures to prevent doxorubicin-induced cardiomyopathy.

The error probabilities alpha and beta are widely used to compute sample sizes and to analyze results of clinical trials. These errors are, however, not the only probabilities to consider when assessing results of clinical studies. The rate of false positive (delta) and false negative (epsilon) results allows one to determine if an experimental finding is likely to reflect the true situation in the population of interest. The delta error is generally high in randomized phase III and in early phase II clinical trials in cancer patients, whereas the epsilon error is relatively low in these settings. This is essentially due to the small probability of detecting a more effective treatment or a new chemotherapeutic agent active in cancer. The delta error could be considerably reduced by increasing the sample sizes and by restricting the allowance made for the alpha error, which should be set at a 1% level as a minimum requirement.

A statistical method for interpreting data on the efficacy of anticancer agents is proposed. Tables were prepared for the retrospective analysis of studies evaluating the activity of anticancer agents against individual tumor types. The number of responding patients and the number of patients entered in the study were used to more objectively and formally determine the future disposition of the drug. Several examples of clinical studies show that use of our tables allows a more satisfactory and reliable classification than is often currently reported.