In a prospective, randomized, double-blind, multicenter study, 202 patients with cancer from 19 medical centers were treated for hypercalcemia of malignancy with daily intravenous infusions of etidronate disodium (136 patients) or saline alone (66 patients) for 3 consecutive days. Patients also received up to 3.25 L of saline daily during the treatment period. Of 157 patients for whom data could be evaluated for efficacy, 63% (72/114) of etidronate-treated and 33% (14/43) of saline-treated patients had a normalization of total serum calcium levels. When serum calcium levels were adjusted for albumin (147 assessable patients), 24% of the etidronate- and 7% of the saline-treated patients responded to treatment. No serious side effects or treatment-related deaths occurred. When accompanied by adequate hydration and diuresis, intravenous etidronate was safe and more effective than hydration and diuresis alone in controlling hypercalcemia of malignancy.

In a randomized multi-center study, 83 patients with small cell lung cancer were randomly assigned to treatment with cisplatin 100 mg/m2 intravenously (IV) day 1 and etoposide 120 mg/m2 IV days 1, 2, and 3 or cisplatin 100 mg/m2 IV day 1 and etoposide 120 mg/m2 IV day 1 and 240 mg/m2 orally days 2 and 3. Both regimens were repeated every 4 weeks. Prior to randomization, patients were stratified by extent of disease, performance status, and gender. A total of 41 patients were randomly assigned to the parenteral treatment only regimen, and 42 patients received cisplatin and IV/oral etoposide therapy. Both treatment arms were comparable regarding patient characteristics. Limited disease (LD) patients constituted 52% and 49% of the patient population for the oral and IV etoposide regimens, respectively. The overall complete response (CR) and partial response (PR) rate was 50% (95% confidence interval [CI] 35% to 65%) for the oral etoposide regimen and 59% (95% CI 44% to 74%) for the IV etoposide regimen (P = 0.438). For both regimens, 55% of the LD patients achieved either CR or PR. Time to progression and survival were comparable for both treatment arms. Hematologic toxicity was comparable in both treatment arms, with 80% of patients experiencing grade 3 or 4 neutropenia or thrombocytopenia. Moderate to severe anemia and weight loss were more predominant with the IV than with the oral regimen.

A questionnaire was developed to evaluate internists' perceptions about patients' survival of cancer as compared with other diseases. The questionnaire consisted of four pairs of survival-matched cancer and non-cancer diseases. The questionnaire was administered to 42 faculty members and 37 resident physicians in the Department of Medicine at the University of Missouri-Columbia. Physicians rated patients' survival of cancer to be significantly lower than patients' survival of comparable non-cancer diseases (p less than 0.001). Resident physicians estimated patients' survival of breast cancer to be significantly lower (p less than 0.007) and estimated the survival of lung cancer to be significantly higher than the faculty members' estimate (p less than 0.003). These physicians' perceptions could adversely affect the quality of care and the degree of consideration given to both cancer and non-cancer patients. The differences observed in faculty members' and resident physicians' responses were attributed to the greater knowledge and clinical experience of faculty rather than differences in attitudes toward cancer.

Multiple mechanisms are involved in the pathophysiology of thrombosis in cancer. It is highly likely that, in an individual patient, a multifactorial etiology is operative. The three basic mechanisms for hypercoagulability in cancer are interrelated to a degree and probably are also the mechanisms involved in metastasis in addition to thrombosis. Manipulation of coagulation in the cancer patient has the potential to prevent complications, abrogate metastasis, and potentially prolong survival.

Esorubicin (4′-deoxydoxorubicin, DxDx) has undergone extensive Phase II investigation for the treatment of cancer. Based on in vitro and animal data, esorubicin may possess less myocardial toxicity when compared to doxorubicin. One hundred thirty-six patients with histologically or cytologically documented non-small cell lung cancer or advanced breast cancer were enrolled in two concurrent CALGB clinical trials using esorubicin at a dose of 30 mg/m2 administered intravenously every 21 days. No patient had previously received an anthracycline agent or had evidence of severe cardiovascular disease. Cardiotoxicity was observed in eleven patients. Four patients developed symptoms of congestive heart failure and three asymptomatic patients had a significant fall in left ventricular ejection fraction (LVEF) as measured by gated pool heart scan. Four patients had cardiac signs or symptoms of indeterminate relationship to esorubicin therapy. Of 44 patients receiving more than four cycles of therapy, 36 patients (82%) had serial gated pool heart scans permitting assessment of subclinical myocardial toxicity. A 5% drop in LVEF was observed following approximately 240 mg/m2 esorubicin; a 10% drop was observed after approximately 480 mg/m2. If further clinical studies are undertaken with esorubicin, investigators are advised to monitor cardiac function frequently once the cumulative esorubicin dose exceeds 240 mg/m2. If congestive failure appears during therapy, prompt cessation of esorubicin and institution of inotropic agents may provide effective palliation. Normal myocardial function may be restored within several months.

Detailed records were maintained prospectively of all medications taken by 719 patients with advanced carcinoma of the lung or colon. Of this total, a cohort of 19 patients was identified who had ingested incidentally either nifedipine, diltiazem, verapamil, or trifluoperazine in standard therapeutic doses for a minimum of one month and a mean of 5.8 months and median of three months. Treatment with these calcium antagonists was well tolerated and, upon comparison with otherwise comparable patients who did not ingest a calcium antogonist, appeared to be associated with certain favorable outcomes, including delayed tumor progression and prolonged survival. These preliminary findings suggest that beneficial effects of such drugs observed with chronic treatment in experimental animal tumor models may occur in human disease and that definitive prospective, randomized, clinical trials of calcium antagonists administered continously in ordinary therapeutic doses are both feasible and justified.

The initial care of patients with acute nonlymphocytic leukemia can be lifesaving. Such patients are most often treated at tertiary care centers where resident physicians, working under the supervision of a subspecialist, are responsible for the diagnosis and initial treatment. During the first 48 hours, the house officer must recognize and understand the management of perilous complications such as hyperleukocytosis, hemorrhage, and infection. Specific lifesaving measures will grant the patient and his physicians sufficient time to reach a decision regarding the initiation of curative induction chemotherapy.

Epidural spinal cord compression is a common complication of malignancy. In the majority of cases, the primary site is known at diagnosis or is evident following limited investigation. During the period January 1975 to December 1987 we encountered seven cases of tumor of unknown origin presenting as cord compression. Myelography detected the site of cord involvement in six cases, and computed tomography of the spine was utilized in one case. All seven patients underwent laminectomy. Histologic diagnosis was adenocarcinoma in four cases, squamous in one case, and large cell undifferentiated carcinoma in two cases. Evaluation for a primary site was unrewarding. Prognosis was poor, with a median survival of 10 weeks. Only one patient had a satisfactory response to treatment.

Department of Medicine, Hematology, and Medical Oncology, Harry S. Truman Memorial Veterans Haspital, Columbia, Missouri

Of 129 patients with small cell lung cancer (SCLC) who underwent bone marrow examination for staging, 39 (30%) had bone marrow involvement. Only three of 129 patients (2.3%) had bone marrow involvement as the only site of metastatic disease. When patients with bone marrow metastasis were compared with patients whose bone marrow was normal, there were significant differences in serum levels of lactate dehydrogenase (LDH), glutamic oxalacetic transaminase (SGOT), glutamic pyruvic transaminase (SGPT), alkaline phosphatase (AP), albumin, and sodium (Na). We found no clinically significant difference in survival between patients with extensive disease with or without bone marrow involvement. Serum Na, albumin, SGOT, and uric acid were important prognostic determinants of survival. Based on the results of this study, we do not recommend routine bone marrow examinations in the staging of SCLC.

During the third-year medicine clerkship, students were instructed in online computer Physician Data Query (PDQ) searches. Each student completed computer searches in at least one of five tumor topics. Students assigned to selected tumor topics performed significantly better on test questions in their assigned topic as compared to the scores of students who were not assigned that topic. Although students were encouraged to use the PDQ ad libitum, within three months of completing the clerkship, only 22 students (20%) had conducted additional searches. We conclude that PDQ instruction may enhance students' knowledge about cancer. Student instruction can be effectively completed with minimal computer time. The results from our program evaluation and the limited student use following completion of the clerkship suggest that we should identify another user group, such as senior housestaff, to generate greater interest and more frequent use of the PDQ.

Fifty-one patients with primary myelodysplastic syndrome were prospectively evaluated using a scoring system based on the presentation blood and bone marrow findings. Twenty-four patients (47%) evolved to acute nonlymphocytic leukemia. Stepwise regression model showed that the scoring system was the only significant variable for predicting transformation to acute leukemia (p = 0.0007, sensitivity 70.8%, specificity 77.8%). Seventy-six percent of patients with a score of 14 or greater developed acute leukemia compared to 19% with a score of 13 or less. Median survival of the entire group was 10 months. The most important prognostic factor for predicting survival was the scoring system (p = 0.0001). Survival correlated inversely with the score. This scoring system may be useful in the management of patients with myelodysplasia.

Dysplastic hematopoiesis associated with erythrocyte macrocytosis is a morphologic hallmark of myelodysplasia. We report the cases of six patients with myelodysplasia in which acanthocytosis was the predominant red blood cell (RBC) abnormality. In each case acanthocytes represented 5% to 10% of circulating RBC forms and was the primary reason for referral in two cases. None of the patients had comorbid conditions known to be associated with acanthocyte formation. Myelodysplasia should be considered in the differential diagnosis of acanthocytosis, particularly in the anemic, elderly individual. Acanthocytosis may be a harbinger of an unrecognized, hematologic stem-cell disorder.

To determine the clinical characteristics of patients presenting with malignant ascites, as well as means of evaluating the outcome of patients with the disease, a retrospective review was conducted of all cases of malignant peritoneal effusions diagnosed from 1978 to 1987 at a University Hospital and a Veterans Administration Hospital. Of 65 patients with malignant ascites (40 women; 25 men), the primary site was known in 51 cases (80%). Common sites in women were the ovaries, endometrium, and cervix; in men, common sites were the colon, rectum, and stomach. For five women and nine men the primary site was unknown. Median survival from diagnosis was 7.5 days (mean, 43 days; range 1-256 days). Chest radiograph and abdominal computed tomography (CT) scan did not disclose the occult primary. An occult primary was detected while the patient was alive in only two cases and at autopsy in two other patients. Due to the poor prognosis for this disease, we do not recommend an aggressive approach to malignant ascites of unknown origin, except perhaps in women, in whom ovarian cancer should be suspected.

Results of bone marrow biopsy were retrospectively evaluated in 120 previously untreated patients with Hodgkin's disease. The incidence of bone marrow involvement was 13%. All patients with marrow invasion had B symptoms and/or clinically advanced disease. When patients with bone marrow involvement were compared to those without there were significant differences in the incidence of B symptoms, the clinical stage, hemoglobin levels, leukocyte counts, platelet counts, and serum levels of lactate dehydrogenase and alkaline phosphatase. None of 59 patients with clinical stage IA and IIA had evidence of marrow invasion. This study demonstrates that trephine bone marrow biopsy is of value in detecting marrow involvement in specific subgroups of untreated patients with Hodgkin's disease, i.e., those patients with constitutional symptoms and/or clinical stage III or IV. However, bone marrow biopsy adds little to the initial staging of patients with clinical stage IA and IIA. Routine use of this procedure in such patients may be unnecessary.

Due to shorter hospitalization periods and changes in surgical procedures, breast cancer patients have less inpatient contact with rehabilitation resources. A questionnaire related to educational needs and social support was mailed statewide to 2,000 postmastectomy women who had received a Reach to Recovery visit. The findings are based on quantitative data reported by 933 women and from 27 women in follow-up interviews. Respondents ranked their educational needs in six categories from greatest to least importance as follows: (1) information about breast cancer, (2/3) personal hygiene/exercise and nutrition/weight control (both ranked of equal importance), (4) prosthesis/clothing information, (5) social support, and (6) sexual issues. Performance on the knowledge assessment correlated directly with the amount of educational experience and inversely with age. Respondents who lived in communities of less than 2,500 were less informed than those from other locations. Participation in formalized support groups was infrequent (11%). The major source of information was the media, with 88% indicating they would watch television programs about breast cancer. Thirty-three percent of the respondents indicated they owned a video cassette recorder (VCR); about 93% said VCRs were available for rent in their community. Work associates were identified as a group that encouraged information seeking; health care professionals were the most successful in motivating women to participate in support groups.