Faculty Bibliography

Current cooperative group trails in non-Hodgkin's lymphoma have been analyzed for their overall methods and strategies. There has been more frequent application of staging procedures and individualization of protocols for favorable and unfavorable histologies according to the Rappaport classification. Early-stage protocols are evaluating the extent of radiotherapy and the need for chemotherapy as maintenance. In later stages the incorporation of new agents in induction regimens, use of cycle-active agents, development of non-cross-resistant combinations, and use of radiation in bulk disease are being examined. In childhood lymphoma, strategies using both leukemia- or lymphoma-type approaches are being tested. Cooperative group trials should also serve as an extensive repository of data on late effects of treatment and on alterations of the course of the disease for future analysis.

Twenty-six investigational anticancer drugs formerly supplied by the National Cancer Institute are no longer available due to the lack of requests for their use in clinical trials. This report examines the data on these drugs to determine how well they were clinically evaluated. Generally, the studies are incomplete, and 34% of the compounds have not been studied beyond phase I trials. Clinical pharmacology data were not obtained for most of the drugs. In addition, the information available for drugs that did undergo phase II trials is grossly inadequate and does not permit a confident decision to withdraw them from investigational use. Instances of "hints" of activity and interesting drug properties are cited to stimulate further study. Finally, a list of compounds scheduled for future termination is given within the framework of this analysis to provoke thought toward obtaining more phase II data before these drugs fall into disuse.

A quick method of concentrating cancer cells and the preparation of cytological slides from body fluids and aspirates is described, using a single Ficoll gradient and cytocentrifuge. The method eliminates the disadvantages of conventional techniques, i.e., excess contamination by red (erythrocytes) or white (leukocytes) blood cells and a scarcity of cancer cells. Because the technique is simple and requires only standard cytotechnological equipment, it can be easily adopted as an aid to diagnostic routine in cancer cytology.

VM 26 and VP 16-213 are epipodophyllotoxin analogs. This paper presents a comparative analysis of their experimental and clinical features but fails to disclose any significant difference between these drugs. Similar studies with other classes of compounds might help to define some rationale for the development of analogous cytotoxic agents.

Eight of 11 consecutive patients with metastatic endometrial adenocarcinoma completed more than one course of treatment with a doxorubicin-cyclophosphamide combination. Six of these patients improved, with three showing a complete remission of all disease manifestations and two experiencing an objective partial response (greater than 50 per cent tumor shrinkage). Median duration of all responses was 10 months, with three patients surviving more than one year. Review of patient characteristics suggests that, unlike progestin therapy, this new program is effective in the presence of poorly differentiated tumors and short progression-free intervals. Therefore, chemotherapy should probably supplement progestins in future clinical trials and should certainly be considered when hormone therapy fails in advanced endometrial cancer. Moreover, if the degree of efficacy reported herein is confirmed, it will justify clinical trials that include patients in earlier stages of disease.

Cis-diamminedichloroplatinum (II) (DDP) leads the series of platinum coordination complexes, a new class of cytotoxic agents. The antitumor and toxic effects of this drug are discussed. It has displayed encouraging results in testicular tumors. The drug's therapeutic effectiveness has also been recognized in a variety of other solid tumors, particularly ovarian, bladder, and head and neck malignancies. Gastrointestinal, renal, audiologic, and relatively minor hematologic toxicities may be encountered, but promising methods have been developed to increase the therapeutic index of DDP.

The results of trials testing combined surgery and chemotherapy in lung cancer are reviewed. Fifteen adjuvant trials using various chemotherapeutic agents were analyzed to determine reasons for their lack of success. Current trials with adjuvant therapy in lung cancer are briefly outlined. In addition, analysis of the activity of chemotherapeutic agents in advanced lung cancer and its implications in the design of future adjuvant studies are detailed.

Estramustine phosphate is a nitrogen mustard derivative of estradiol that has been advocated for the treatment of prostatic cancer. The compound was designed with the hope that the estrogen moiety would direct the alkylating moiety to estrogen-dependent malignancies, where the alkylating moiety would be released specifically. Preclinical and clinical data are reviewed to determine to what extent that challenging concept is fulfilled. In addition, we have examined critically the efficacy of this drug for the treatment of prostatic cancer. From available data it appears that there is no evidence that the alkylating moiety of estramustine phosphate is specifically freed in estrogen-dependent tissues. Estramustine phosphate appears to be an active compound with acceptable toxicity in prostatic cancer. However, further clinical trials must be undertaken to clarify the future role of estramustine phosphate in the treatment of prostatic cancer.