Sherwood P. Miller

Role of Gamma Globulin for Immunoprophylaxis in Multiple Myeloma

BACTERIAL infection is one of the leading causes of morbidity and mortality in patients with multiple myeloma.1 , 2 Although most patients have large amounts of homogeneous myeloma immunoglobulin p...

Clinical studies of dichloromethotrexate (NSC 29630)

Dichloromethotrexate (DCM) is much superior to methotrexate (MTX) in inhibiting L1210 leukemia and C3H lymphosarcoma in mice. This greater effectiveness obtains for parenterally administered DCM and is much less apparent when DCM is given by mouth. The toxicity of DCM in animals is qualitatively similar to that produced by MTX. DCM is fifty to one hundred fold less toxic than MTX in rats and mice but only tenfold less toxic in dogs. It is concluded from clinical studies reported in this paper that: (1) The tolerated dose of DCM is fivefold that of MTX and the toxic manifestations are similar. (2) The tolerated doses of oral and iniramuscular DCM are equivalent. (3) Equitoxic, and presumably optimal, doses of oral DCM, oral MTX, and intramuscular DCM produce comparable antitumor effects in adults with lymphosarcoma and Hodgkins disease. There is complete tumor regression in 10 to 20 per cent and partial regression in another 20 to 30 per cent of patients. These tumor regressions are, in general, short‐lasting. (4) The dose response relationship is steep. A twofold difference in dose of DCM or MTX results in a significant difference in toxicity and antitumor effect. (5) There are at least four other more effective modalities of treatment for lymphoma which should be employed before conventional folic acid antagonist therapy is considered.

A CLINICAL PHARMACOLOGIC STUDY OF CHEMOTHERAPY AND X-RAY THERAPY IN LUNG CANCER.

Abstract Actinomycin D and 5-fluorouracil, given with x-ray in a dosage regimen sufficient to produce definite but tolerable gastrointestinal and marrow toxicity, did not increase the percentage of patients with carcinoma of the lung showing shrinkage of lesions in the irradiated field. There was no evidence of a more rapid onset of shrinkage of the tumor or of an additive effect at subtotal doses of x-ray. Patient survival was not affected beneficially by the addition of the chemotherapeutic agents. Toxicity was not correlated with responses induced. Patients classified as responders to therapy lived longer than those classified as nonresponders.

Cytologic studies of enzymes in malignant tissues

The techniques of enzyme cytochemistry have been applied to a study of aspirated and smeared malignant cells and to bone marrow cells. Analysis of the enzyme activity of cells from 240 specimens was carried out. By determining characteristic enzyme activity patterns with 4 enzymes, namely acid and alkaline phosphatase, aminopeptidase and nonspecific esterase, it has been possible to derive patterns for a number of tumors which can aid in the diagnosis of the primary site of origin of metastatic lesions. Distinction between anaplastic carcinomas of some types and lymphoreticular sarcoma is possible on the basis of enzyme studies. Similar distinctions appear to be true for lung and genitourinary tract carcinomas but it was not feasible to determine a general method to distinguish all anaplastic carcinoma from sarcoma. Further study of the diagnostic value of this technique appears to be warranted.

Cytologic studies of glucose‐6‐phosphate dehydrogenase in malignancy

A histochemical technique for the determination of glucose‐6‐phosphate dehydrogenase (G6PD) was combined with cytologic studies of malignant tumor cells obtained by aspiration biopsy and touch preparations. Consistently high levels of G6PD activity were found in carcinoma cells of the colon. Lung cancer cells showed no or very weak enzyme activity in most cases. Wide variations in the level of this enzyme activity were noted in carcinoma of the breast and ovary while moderately strong activity occurred in cells from hypernephroma. Lympho‐proliferative diseases and soft tissue sarcomas also showed little or no activity. When combined with other cytohistologic enzyme determinations, patterns of enzyme activity corresponding to particular tissue origins became apparent.

COMPARATIVE EVALUATION OF COMBINED RADIATION-CHLORAMBUCIL TREATMENT OF OVARIAN CARCINOMATOSIS

In a study conducted by the Eastern Cooperative Oncology Group, 51 evaluable women with advanced ovarian carcinoma were randomized to either abdominal radiation therapy alone, chlorambucil alone, or to a combination of radiation therapy and chlorambucil by members of the Eastern Cooperative Oncology Group. Provision was made for crossover therapy for patients who were nonresponders to a single modality of treatment. Parameters followed included objective and subjective response rates and patient survival. The total response rate was 51%, with no significant difference among the three treatment regimens. Regarding survival, radiation therapy alone was significantly superior to the other regimens, with an average survival of 94.9 weeks. Best results were obtained in patients with normal performance status; for this group, radiation therapy alone offered the best chance for prolonged survival.