Robert L. Capizzi

Acute nonlymphocytic leukemia: a delayed complication of Hodgkin's disease therapy: analysis of 109 cases.

The use of combined modality therapy (irradiation and combinations of drugs) in the treatment of Hodgkins disease has produced a significant improvement in survival, during which most patients lead an active and productive life. The estimated 1% incidence of leukemia in treated Hodgkins disease patients, however, is greater than would be expected in the general population. There is a vast amount of literature which indicates that alkylating agents, procarbazine and irradiation are leukemogenic and immunosuppressive in animals and man. It is then conceivable that the current intensive treatment programs which use these agents are promoting the development of acute non‐lymphocytic leukemia (ANLL). This leukemia has occurred most often in patients whose Hodgkins disease is poorly controlled and who have received more aggressive therapy. The latent period from the diagnosis of Hodgkins disease to the diagnosis of leukemia is significantly shorter (p < .0005) in those patients who have received intensive and near maximal radiotherapy (total nodal irradiation), combination chemotherapy (MOPP or equivalent) or a sequential combination of the two modalities than similar patients who were treated with less than total nodal irradiation and or single agent chemotherapy. The following characteristic features have occurred with sufficient frequency to suggest that the subsequent leukemia is a distinct clinicopathological entity: pancytopenia, megaloblastoid marrow, nucleated red blood cells in the peripheral blood, random chromosomal aberrations of the bone marrow in most patients (94%), and refractoriness to antileukemia therapy (response rate 6.5%) with a very short survival (median one month).

L-Asparaginase: Clinical, Biochemical, Pharmacological, and Immunological Studies

Abstract Forty patients with acute leukemia were treated with Intravenous L-asparaginase in doses ranging from 10 to 1,000 international units/kg body weight per day for 2 to 20 days. Most had long...

The role of chemotherapy in the management of cancer of the head and neck: A review

Although experience with drug therapy of advanced or recurrent squamous cell carcinoma of the head and neck is limited, several agents have produced convincing and reproducible tumor regression in these patients. Methotrexate has had the widest usage, and produces 30–50% response rates; bleomycin, hydroxyurea, and adriamycin appear to be somewhat less effective. Location of the malignancy and previous x‐ray treatment appear to be important determinants of responsiveness to methotrexate, while degree of differentiation has not yet been shown to be an important factor for response to this drug. Attempts to improve the response rate and duration of the chemotherapeutic response by utilizing combinations of drugs, or use of drugs to sensitize the tumor to x‐ray treatment, or to reduce the bulk of tumor before x‐ray treatment, are reviewed; they have been only moderately encouraging. Intra‐arterial chemotherapy appears to have a therapeutic advantage over intravenous treatment; however, the morbidity associated with the former approach limits its usefulness for routine usage. The use of drugs as adjuncts following surgery and/or radiation therapy or immunotherapy are newer approaches that have not been investigated sufficiently, but are promising areas for investigation.

Methotrexate therapy of Wegener's granulomatosis.

Abstract Two patients with advanced Wegeners granulomatosis, one with nose, sinus, and skin involvement and the other with pulmonary, renal, and skin involvement, experienced marked improvement wi...

RECENT STUDIES ON THE ANTIVIRAL AND BIOCHEMICAL PROPERTIES OF 5‐HALO‐5'‐AMINO‐DEOXYRIBONUCLEOSIDES *

Therapy of nonlethal virus infections with nucleoside analogs that are subsequently incorporated into cellular DNA has a number of potential drawbacks. Incorporation into DNA of highly proliferative cell types, such as found in intestine, bone marrow, and lymphoid tissues, may produce unacceptable cytotoxicities as well as possibly inducing carcinogenesis or mutagenesis. The availability of nucleoside antiviral agents that cannot be phosphorylated by normal, noninfected cells would offer significant therapeutic advantages. A major conceptual contribution toward this objective was made by Langen and c o ~ o r k e r s ~ ~ when they prepared analogs of thymidine that contained various halogens in the 5’ position. These compounds preferentially inhibit thymidylate kinase but are not phosphorylated nor are they incorporated into DNA in vivo. These observations provided the stimulus for our studies on the biological activity of 5’-amino nucleoside analogs. Further impetus was

Principles of Combination Chemotherapy

In 1948, Farber (Farber et al.,1948) reported that the folic acid antagonist aminopterin was able to induce temporary clinical remissions of disease in some children with acute leukemia. Remarkable as these early remissions were, it soon became apparent that with the exception of methotrexate-induced cure of choriocarcinoma (Li et al.,1956) (and later cyclophosphamide-induced cure of Burkitt’s lymphoma) (Nkrumah and Perkins, 1976; Ziegler et al., 1973), single-agent chemotherapy yielded only a low percentage of complete responses of relatively short duration. Early studies in the 1960s utilizing combinations of antineoplastic drugs soon demonstrated the superiority of combination chemotherapy over single agents in the treatment of certain tumors. Using the combination of methotrexate, actinomycin D, and chlorambucil for the treatment of advanced testicular carcinoma, Li et al. (1960) demonstrated a marked improvement in the response rate as compared with the effect of these agents when used alone. Greenspan (Greenspan et al., 1963; Greenspan, 1966) showed that the objective response rate in metastatic breast carcinoma was more than double the single-agent response rate when thioTEPA and methotrexate were used in combination. When 5-fluorouracil (5-FU) was added to the combination, some patients with hepatic metastases resistant to the drugs used alone showed significant tumor regression. The therapeutic potential of combination chemotherapy became more impressive with the demonstration of the superlative effect of five drugs in the treatment of advanced breast cancer (cyclophosphamide, vincristine, methotrexate, prednisone, and 5-FU) (Cooper, 1969). Subsequently, a large number of laboratory and clinical trials against both animal and human tumors followed that utilized empirical combinations of previously known active drugs.