Daniel E. Lehane

Preliminary Observations of the Effects on Breast Adenocarcinoma of Plasma Perfused over Immobilized Protein A

PROTEIN A, a constituent of the cell wall of Staphylococcus aureus Cowans 1 (SpA), reacts with the Fc region of immunoglobulins from many mammalian species and combines with immune complexes in ser...

Phase III comparison of the treatment of advanced gastrointestinal cancer with bolus weekly 5‐FU vs. methyl‐CCNU plus bolus weekly 5‐FU. A southwest oncology group study

In a randomized and stratified study, 294 patients with advanced gastrointestinal cancer were treated either with 5‐fluorouracil (5‐FU) 400 mg/m2 weekly intravenously (i.v.) or 5‐FU 400 mg/m2 i.v. weekly plus methyl‐CCNU 175 mg/m2 orally (p.o.) every 6 weeks. The response rate in colorectal cancer with 5‐FU was 9.5% while the two‐drug treatment produced a response of 31.8% (p = .009). The response in all gastrointestinal cancers to 5‐FU was 10.6% as compared with 29.3% for the combination (p = .012). All responses were partial. The two‐drug regimen is more effective and more toxic than weekly 5‐FU therapy.

Prinzmetal's angina during 5-fluorouracil chemotherapy

Variant angina developed during intravenous 5-fluorouracil therapy in a patient without prior history of angina pectoris. Ambulatory electrocardiography demonstrated S-T segment elevation and ventricular ectopy during pain, whereas no symptoms or S-T segment changes occurred during placebo therapy. Prophylaxis with both nifedipine and diltiazem was successful in preventing recurrence. It is believed that 5-fluorouracil induced coronary vasospasm and that this was prevented by prophylactic calcium antagonist therapy. Drug-induced coronary artery spasm may be the cause of 5-fluorouracil-associated chest pain.

Long-term survival and toxicity in small cell lung cancer. Southwest oncology group study

In the first study of combined chemotherapy and radiation therapy for small cell lung cancer by the Southwest Oncology Group, 17 patients survived more than five years after treatment was initiated (4.6 percent). Late relapse, or a second primary malignancy three to six years after diagnosis, accounted for death in five of these patients. Late recurrences involved the chest, bone, and liver; none occurred in the central nervous system. Disease-free survival continues in 10 patients (6 percent of those with limited disease and 1 percent of those with extensive-stage diseases) at a minimal follow-up in excess of six years. One definite case of chronic treatment-related toxicity occurred: congestive cardiomyopathy after 450 mg/m2 of doxorubicin, successfully managed with digitalis and diuretics. One severe neurologic problem (orthostatic hypotension with preterminal dementia) and two less severe neurologic complications (occasional falling episodes without documented cause and cerebrovascular accident) may be treatment-related. Progressive pulmonary disability, post-herpetic pain syndromes, organic brain syndrome, and hematologic abnormalities have not been observed to date. Nitrosourea administration and/or co-administration of a nitrosourea or methotrexate during the induction phase of treatment with radiotherapy to the brain may account for the higher incidence of complications observed by others in long-term survivors.

The effect of diuretic pre-treatment on clinical, morphological and ultrastructural cis-platinum induced nephrotoxicity

Abstract The clinical, microscopical and ultrastructural effects of cis -platinum induced nephrotoxicity and the effects of pre-treatment with mannitol, furosemide (Lasix) or both diuretics in male Holtzman rats is described. Cis -platinum administered intraperitoneally at doses ranging from 2.5–7.5 mg/kg was associated with dose-dependent BUN and creatinine elevation; however, weight loss, which averaged 13%, was not dose dependent. Mannitol (4 g/kg) administered immediately prior to cis -platinum, or furosemide (2 or 12.5 mg/kg) administered either concomitantly or 30 minutes prior to cis -platinum, had no effect on BUN or creatinine elevations. Varying the route or time of furosemide administration did not alter the severity of nephrotoxicity but higher doses of furosemide were associated with more severe BUN elevation. Light microscopy of renal tissue demonstrated that the principle lesion corresponding to cis-platinum injury consisted of coagulative necrosis of tubular epithelium at the corticomedullary transition zone. Glomeruli showed no observable injury. The electron microscopy confirmed the observations from light microscopy, showing injured proximal tubular cells, with loss of the characteristic nuclear electron density, segregated nucleoli and cytoplasmic degeneration. The basement membrane of the proximal tubule, the distal tubular cells and the glomeruli were perserved. Analogous to the nephrotoxicity of aminoglycoside antibiotics, diuretic treatment of animals receiving cis -platinum aggravates rather than ameliorates nephrotoxicity.

Immunocompetence in Advanced Cancer Patients prior to Chemotherapy

A panel of immunologic tests were used to characterize the levels of immunocompetence in 30 patients with advanced lung and head and neck region cancer prior to their receiving chemotherapy. All cell-

Oral fluorouracil therapy of hepatoma

Oral fluorouracil was administered weekly to 12 consecutive patients with unresectable hepatoma. Six patients showed an objective response with a significant increase in survival duration compared to nonresponders and to untreated patients. The clinical features of these cases are discussed, along with details of therapy, and possible reasons for the encouraging results noted with this treatment regimen.

Acquired factor VIII inhibitor in a patient with mycosis fungoides

Acquired factor VIII inhibitors have been noted in patients with hemophilia A (factor VIII deficiency), in nonhemophilic individuals with various collagen‐vascular diseases, in certain normal women following parturition, and occasionally in elderly individuals with no underlying diseases. This study describes the first reported instance of a factor VIII inhibitor in a patient with mycosis fungoides who had bleeding manifested by gross hematuria. Treatment with corticosteroids and cryoprecipitate was followed by cessation of hematuria within two weeks. The patient had one episode of shoulder pain presumably related to hemarthrosis. Immunosuppressive therapy with cyclophosphamide was instituted in an attempt to decrease antibody production and control skin involvement of mycosis fungoides. Factor VIII inhibitor level rose to 1000 Bethesda units without further serious bleeding. There was no peripheral blood evidence of Sézary syndrome. It is possible that some patients with cutaneous T‐cell lymphomas, such as mycosis fungoides and Sézary syndrome, may have an increase in helper T‐cells which may lead to excessive B‐cell activity and overproduction of antibodies.

The nitroblue tetrazolium test in patients with advanced neoplastic diseases.

The nitroblue tetrazolium test (NET) was evaluated in 111 patients with cancer. Patients were placed into control and “presumed infected” groups. The mean NBT score for the control group, 6.3, was significantly greater than the mean for a group of normal volunteers, 3.1, but the mean score for the “presumed infected” group, 15.6, was significantly higher. Less than 10% of the patients with bacterial infection had scores below 10, while 15% of the control patients had unexplained high scores. A method for concentrating leukocytes is described which makes the NBT test feasible in patients with granulocytopenia. Morphological changes in granulocytes used as indicators of infection are unreliable markers in cancer patients, in whom such changes occur frequently in the absence of infection. We have found that the NBT test is more useful as an indicator of infection in patients with cancer.