The effects of bleomycin on immunocompetence in man.

Bleomycin was administered to six patients with advanced cancer. Multiple parameters of both antibody- and cell-mediated immunity were followed serially to characterize the effects of bleomycin on immunocompetence in humans. Antibody-mediated immunity, including primary vaccination with keyhole limpet hemocyanin, was not depressed. While there was no significant suppression of cell-mediated immunity, phytohemagglutinin-stimulated lymphocyte blastogenesis was reduced after treatment with bleomycin. The in vitro effects of bleomycin on lymphocyte stimulation were studied, and while thymidine incorporation was significantly inhibited by bleomycin, leucine incorporation was not reduced even at high concentrations of bleomycin. We have concluded that bleomycin does not suppress immunocompetence in man.

Nuclear and nucleolar ultrastructure of Sézary cells.

Sézary cells were studied in the peripheral blood and characteristic skin lesions of the Sézary syndrome and mycosis fungoides by transmission electron microscopy to obtain more information on their nuclear and nucleolar ultrastructure. Sézary cells contain nucleoli with nucleolonemas or ring-shaped nucleoli similar to those of lymphoblasts and mature lymphocytes. "Maturation asynchrony" of the nucleolus and cytoplasm was evident in some cells that contain large numbers of ribosomes and ring-shaped nucleoli and in other cells that contain nucleoi with nucleolonemas and few ribosomes. The maturation asynchrony of the nucleolus and the cytoplasm, the presence of mitochondrion-like inclusion bodies in the nucleus, and fusion of mitochondria with the nucleus in Sézary cells are ultrastructural abnormalities of this neoplastic lymphocytic variant. The presence of the intranuclear "mitochondrion-like" inclusion body and nuclear rodlets in Sézary cells were exceptional findings.

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.

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.

The nitroblue tetrazolium test in patients with advanced neoplastic diseases.

The nitroblue tetrazolium test (NBT) 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 percent of the patients with bacterial infection had scores below 10, while 15 percent 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.

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 100 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.

Primary liver amyloidosis producing obstructive jaundice.

Liver amyloidosis is very rare but is relatively common within the group of amyloid diseases. Jaundice seldom accompanies this condition. Since the results of liver tests are often abnormal, liver amyloidosis cannot be diagnosed by symptoms alone. Diagnosis is provided only by liver or rectal biopsy. We have described an elderly woman with vague digestive symptoms for several months and jaundice for two weeks before hospitalization, and in whom exploratory laparotomy showed amyloidosis causing obstructive jaundice.

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.

Intra-arterial cisplatin treatment of adenoid cystic carcinoma.

Adenoid cystic carcinoma (ACC) is unique among salivary gland tumors in both its natural history and in its response to nonsurgical treatment methods (ie, radiation and chemotherapy). The chemotherapeutic agent, cisplatin, seems to be unique in its ability to affect ACC. It might be that ACCs of the minor salivary glands are especially vulnerable to the intra-arterial method of administering this drug, because there are accessible feeding vessels to most locations in which these tumors occur. We have treated four patients with advanced ACC with intra-arterial cisplatin. The responses suggest that this method may be a useful adjunct in the management of this tumor both as a preoperative and as a palliative measure.

Comparison of methotrexate and cisplatin for patients with advanced squamous cell carcinoma of the head and neck region: a Southwest Oncology Group Study.

One hundred eligible patients with inoperable, locally advanced or metastatic squamous cell carcinoma of the head and neck region following prior therapy were randomized to receive im methotrexate (50 patients) or iv cisplatin (50 patients). Methotrexate produced a complete plus partial response rate of 16.0% and cisplatin produced a partial response rate of 8.0%, with median durations of response of 18 and 8 weeks, respectively. The corresponding median survival times were 20 and 18 weeks. Methotrexate responders survived 60 weeks, versus 17 weeks for nonresponders. The corresponding survival times for cisplatin-treated patients were 38 and 18 weeks. Good pretreatment performance status had a significantly positive effect on survival (P = 0.04), but prior therapy did not. Toxicity secondary to either agent occurred with the expected frequency. The two agents examined showed comparable antitumor activity in patients with squamous cell carcinoma of the head and neck who had not previously received chemotherapy.

Ocular and orbital complications of intraarterial cisplatin. A case report.

Despite advances in neurosurgery, radiation oncology, and chemotherapy, the prognosis for glioblastoma multiforme remains poor, with a median survival time of 11-12 months. Cisplatin (cis-diamminedichlorideplatinum II) is one treatment for glioblastoma multiforme. Higher response rates have been achieved by intraarterial (i.a.) infusion than by systemic infusion of this agent. Cisplatin therapy may cause neurologic complications, and i.a. delivery has been reported to cause ocular toxicity. We report a patient who experienced intraorbital and intraocular toxicity following supraophthalmic i.a. injection of cisplatin.

Intraarterial cis-platinum chemotherapy for patients with primary and metastatic brain tumors.

A total of 49 patients were treated using intraarterial cis-platinum infusions at a dose of 100 mg/m2. The patients were separated into three groups. There were 13 patients with metastatic tumors, 10 with recurrent malignant gliomas, and 22 patients with high-grade gliomas who received intraarterial cis-platinum as part of an adjuvant program. In addition, four nongliomatous primary brain tumors were treated in this fashion. Cis-platinum was filtered immediately prior to intraarterial infusion using a 0.22-micron filter. Response to treatment was evaluated by follow-up CAT scans and neurologic examinations. There were three complete and eight partial responses in metastatic tumors, and eight partial responses in recurrent gliomas. The median survival was 19 weeks for patients with metastatic disease, and 16 weeks for patients with recurrent gliomas. Those high-grade glioma patients who received intraarterial cis-platinum as adjuvant chemotherapy along with CCNU and radiation therapy had a projected median survival of 91+ weeks. Toxicity from intraarterial cis-platinum following drug filtration was markedly reduced when compared with previous reports. Only five patients experiencing visual or central nervous system toxicity utilizing filtered cis-platinum and no radiographic or histopathologic evidence of central nervous system toxicity was observed. Bilateral deafness was observed following vertebral artery infusion in both patients treated in this manner and thus vertebral artery infusions should be avoided. Systemic toxicity was mild. Intracarotid infusion is a safe, well-tolerated delivery system for filtered cis-platinum with a high response rate for patients with both metastatic and primary malignant brain tumors.

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 with29.3% for the combination (p=.012). All responses were partial. The two-drug regimen is more effective and more toxic than weekly 5-FU therapy.