Jerome B. Block

Varicella-Zoster Infection in Patients with Cancer

Abstract Over a 24-month period, among 419 patients with cancer, zoster occurred in 25% of patients with Hodgkins disease, 8.7% of other lymphoma patients, but in only 1.2% of patients with acute ...

Focused microwave phased array thermotherapy for primary breast cancer

BackgroundA pilot safety study of focused microwave phased array thermotherapy in the treatment of primary breast carcinomas was conducted.MethodsTen patients with breast carcinomas beneath the skin surface that ranged in maximal clinical size from 1 to 8 cm (mean, 4.3 cm) were treated with the breast compressed in the prone position. We planned to deliver a tumor thermal dose equivalent to 60 minutes at 43°C. Breast imaging and pathology data were used to assess efficacy.ResultsFor the 10 patients, the mean tumor equivalent thermal dose was 51.7 minutes, the mean peak tumor temperature was 44.9°C, and the mean treatment time was 34.7 minutes. Ultrasound imaging demonstrated a significant reduction in tumor size (mean, 41%) 5 to 18 days after thermotherapy in 6 (60%) of 10 patients. A significant tumor response on the basis of reduction in tumor size or significant tumor cell kill occurred in 8 (80%) of 10 patients.ConclusionsWith sufficient skin cooling, delivery of focused microwave phased array thermotherapy is safe in treating breast carcinomas when used alone, and some potential efficacy was demonstrated at the tumor thermal doses administered. Increased tumor thermal dose efficacy studies in larger patient populations for improved breast conservation should be investigated.

Significance of blood lactate elevations among patients with acute leukemia and other neoplastic proliferative disorders

Abstract Over a one year period, increases in blood lactate above 10 mEq. per L. occurred in sixteen patients on the Medicine Branch of the National Cancer Institute. In three patients hyperlacticemia was associated with respiratory alkalosis of several days duration. Although the cause of an elevated blood lactate level in respiratory alkalosis has not been definitely established, it is most likely due to an enhancement of aerobic glycolysis by the decreased intracellular hydrogen ion concentration. In thirteen patients, the hyperlacticemia was associated with severe metabolic acidosis. In six, widespread tissue hypoxia was clinically evident. In four of these six lactic acidosis developed after prolonged treatment with vasopressors. In seven patients lactic acidosis developed despite apparently adequate oxygen supply to the tissues. All had acute leukemia and four of these patients had massive, rapidly progressing leukemia. Coincident with a favorable response to antileukemic chemotherapy, lactic acidosis diminished in three of these four patients. Calculations based on in vitro anaerobic acid production by acute leukemic leukocytes suggest that large aggregates of leukemia cells crowded into organs and metabolizing anaerobically may produce sufficient lactic acid to increase the blood lactate concentration markedly and to cause acidosis. Because of the risk of overloading the circulation, and because lactic acid production may be in part pH dependent, cautious alkali administration at a rate sufficient to limit but not fully to compensate the acidosis is recommended. Methylene blue was administered to four patients without demonstrable benefit. Blood L:P (lactate to pyruvate) ratio determinations were considered unreliable indicators of tissue redox potentials because baseline measurements were generally not available, and the effects on the ratios of altered intracellular hydrogen ion concentrations could not be determined.

Hydrazine sulfate influence on nutritional status and survival in non-small-cell lung cancer.

This randomized, prospective, placebo-controlled clinical trial compares the influence on nutritional status and survival of hydrazine sulfate with placebo addition to cisplatin-containing combination chemotherapy in patients with unresectable non-small-cell lung cancer (NSCLC). The trial consisted of 65 patients with advanced, unresectable NSCLC who had had no prior chemotherapy, were at least partially ambulatory (Eastern Cooperative Oncology Group [ECOG] performance status [PS] level 0-2), and who had adequate hematologic, renal, and hepatic function. All patients received the same defined combination chemotherapy (cisplatin, vinblastine, and bleomycin) and the same defined dietary counseling with the addition of either three times daily oral hydrazine sulfate (60 mg) or placebo capsules. Hydrazine sulfate compared with placebo addition to chemotherapy resulted in significantly greater caloric intake and albumin maintenance (P less than .05). Considering all patients, survival was greater for the hydrazine sulfate compared with placebo group (median survival, 292 v 187 days), but the difference did not achieve statistical significance. In favorable PS patients (PS 0-1), survival was significantly prolonged (median survival, 328 days v 209 days; P less than .05) for hydrazine sulfate compared with placebo addition. In a multifactor analysis, PS, weight loss, and liver involvement were the final variables. Objective response frequency and toxicity were comparable on both arms. Hydrazine sulfate may favorably influence nutritional status and clinical outcome of patients with NSCLC. Further definitive studies of hydrazine sulfate addition to therapeutic regimens in NSCLC are warranted.

A randomized comparison of radiotherapy with a radiotherapy–chemotherapy combination in stage IV carcinoma of the head and neck

Between 1975 and 1978, 23 patients with Stage IV, unresectable, squamous cell carcinoma of the head and neck were randomized to receive radiotherapy (RT, 11 patients), or radiotherapy‐chemotherapy (RT & CT, 12 patients). The response rate for the 12 RT & CT patients was four complete remissions (CR) and four partial remissions (PR); the 11 RT patients had one CR and three PR. The presence of a responses (CR or PR) significantly enhanced the median survival (14 vs. 5 months; P = 0.005). The duration of objectives remission was longer among the RT & CT patients when compared with RT patients (6 vs. 2.3 months, P = 0.18). The median survival of the RT & CT group was 12 months compared with 5.6 months for the RT group (P = 0.13). One RT & CT patient remains alive with disease at 44 months, one RT patient remains alive without disease at 30 months. The present chemotherapy regimen did not modify the pattern of failure and only marginally increased patient survival. It did, however, increase the response rate. The authors plan to reactivate the trial with modification in the induction chemotherapy and the addition of postradiation maintenance CT consisting of sequential bleomycin and cis‐platinum.

Effect of large intermittent intravenous doses of cyclophosphamide in lymphoma

Nineteen patients with generalized lymphoma were treated with large intermittent intravenous doses of cyclophosphamide. Five patients experienced a complete response, and 2 had a partial response. The median duration of complete response was 22 months. Toxicity was not intolerable. Published results of response rates in lymphoma to various chemotherapeutic agents are summarized. Factors which contribute to survival in patients with lymphoma are discussed. It is suggested that further evaluation of large intermittent doses of cyclophosphamide be made in view of the favorable results.

Differential pulse polarographic determination of plasma menadione

A differential pulse polarographic assay for plasma vitamin K3 (menadione) has been developed. Details of the assay are (i) lipid-soluble material is extracted from plasma into ether by the method of Bjornsson et al. [(1978) Thromb. Haemostas. 2, 466-473]; (ii) ether is evaporated under nitrogen and the residue is dissolved in the supporting electrolyte, methanol: 0.2 M borate buffer (9:1), pH 6.8; (iii) current height is measured at -0.32 V vs SCE on the differential pulse polarogram. The lower sensitivity limit of this technique after addition of standard vitamin K3 to plasma is 0.3 microM; the calibration curve is linear from 0.6 through 10 microM. Two patients treated with a single dose of menadiol sodium diphosphate, 20 mg/M2 i.m., achieved measurable plasma vitamin K3 levels at 0.5 to 1.0 h ranging between 0.5 (0.08 micrograms/ml) and 2 microM (0.3 micrograms/ml).

Lung Cancer Cachexia

Weight loss in patients with advanced lung carcinoma has been recognized clinically for many years. However, only recently has the prognostic significance of weight loss in patients with this disease been identified. In one report by Costa and co-workers [1] the incidence, timing, and severity of weight loss in a total of 479 patients with lung cancer was related to patient survival. At their initial clinical presentation, 47% of lung cancer patients had lost at least 5% of their usual body weight. The survival of these patients was significantly less than that of patients not experiencing weight loss, even when corrected for factors such as age, sex, extent of disease, cell type and performance score [1]. An analysis of 1,026 patients from the Eastern Cooperative Oncology Group revealed evidence of weight loss during the previous 6 months in 57% of small cell and 61% of non-small cell lung cancer patients [2]. In both categories of lung cancer, median survival was significantly decreased for patients experiencing antecedent weight loss prior to protocol chemotherapy: 34 weeks vs 27 weeks in small cell; 20 weeks vs 14 weeks in non-small cell. The influence of weight loss on survival in these large reports exceeds the current influence of chemotherapy on survival in non-small cell disease. Thus, weight loss at the time of clinical presentation is an important, independent factor prognostic of survival in patients with lung cancer.

Doxorubicin, cyclophosphamide, CCNU, and vincristine with or without cisplatinum in non-small cell lung cancer

To EVALUATE THE ROLE OF CISPLATINUM in the treatment of advanced non-small cell lung cancer, 48 patients received either a doxorubicin (adriamycin) 50 mg/m2 I.V., cyclophosphamide 300 mg/m2 I.V., lomustine (CCNU) 50 mg/m2 p.o., vincristine (on-covin) 1.2 mg/m2 I.V. (ACCO) combination or the same drugs plus cisplatinum 50 mg/m2 I.V. (PACCO) in a prospective sequential trial. No patient had received prior chemotherapy. Patients receiving the two regimens were comparable with regard to median age, performance status, histologic subtype, disease extent, and weight loss. Objective response frequency was only 5% in the initial 20 patients receiving ACCO treatment compared to a response frequency of 28% (7% complete) in the 28 patients receiving cisplatinum in the PACCO treatment arm (p < 0.06). Patients achieving objective response lived significantly longer than nonresponders (9.1 months vs. 3.8 months, p < 0.05). Although median survival was similar on the two regimens (6.1 months for ACCO vs. 7.6 months for PACCO), more than four times as many patients were alive after 1 year in the PACCO treatment group (24% vs. 5%). Predominant toxicity consisted of moderately severe nausea and vomiting (63% on PACCO vs. 34% on ACCO, p < 0.05) and myelosuppression with WBC < 3,000/mm3 occurring in the majority of patients on both regimens. These results suggest cisplatinum addition to a doxorubicin, cyclophosphamide, lomustine, and vincristine combination may be associated with increased 1-year survival in the non-small cell lung cancer patient population.

Water Intoxication and Cyclophosphamide

Excerpt To the editor: We were interested in the article of DeFronzo and his associates, Water Intoxication in Man After Cyclophosphamide Therapy (Ann Intern Med861-869, 1973), which indicates a ...