Combination versus sequential five-drug chemotherapy in metastatic carcinoma of the breast.

Patients with metastatic or recurrent adenocarcinoma of the breast were randomized to weekly combination chemotherapy, intermittent combination chemotherapy, or single-drug chemotherapy administered sequentially. Patients receiving weekly combination therapy were more likely to respond than those receiving single-drug therapy (5-fluorouracil). The median survival for either group treated with combination therapy was double that of patients on sequential therapy. One-fourth of the patients had a prolonged survival (greater than 75 weeks), regardless of therapy.

Eosinophil infiltration of human colonic carcinomas as a prognostic indicator.

In experiments with suspensions of cells from colonic carcinomas, we noted that some colonic carcinomas contain large numbers of eosinophils. We therefore carried out a prospective study with 67 almost consecutive colonic carcinomas in our medical center after optimal fixation and staining for the demonstration of eosinophils. Infiltration of the primary tumor by eosinophils was found to have marked prognostic significance. The proportion (4 of 17 or 23.5%) of carcinomas with more than 30 eosinophils/sq mm that had metastases was significantly less (p = 0.01) than the proportion (31 of 50 or 62.0%) of carcinomas with less than 30 eosinophils/sq mm that had metastases. At 18 months, following the resection of tumor in patients without metastases, all of the patients (9 of 9) with greater than 30 eosinophils/sq mm were alive in contrast to 73.7% (11 of 15) of the patients with less than 30 eosinophils/sq mm. The number of survivors at 18 months for the total population without regard to metastases was significantly greater (p = 0.028) for those with greater than 30 eosinophils/sq mm than for those with less than 30 eosinophils/sq mm. We conclude that the quantitative assessment of eosinophils is one of the most important aspects of the microscopic evaluation of this common human tumor.

Consolidation and maintenance therapy in multiple myeloma: randomized comparison of a new approach to therapy after initial response to treatment.

A randomized, controlled trial was initiated in 1977 to evaluate the impact of three alternative approaches to consolidation and maintenance therapy after initial maximal response for multiple myeloma. All patients were treated initially with BCNU, cyclophosphamide, and prednisone (BCP) until a designated level of response was achieved. Responders were randomly assigned to either melphalan and prednisone (MP); prednisone, Adriamycin (Adria Laboratories, Columbus, Ohio), azathioprine, and vincristine (PAIV), or no therapy until relapse, then treatment with BCP. Initial response rates were comparable with previous trials. A small number of incremental responses were observed with both MP and PAIV. Survival was the same for all three maintenance approaches and the same as that observed in our previous continuous BCP or MP therapy. Additional or consolidation/maintenance therapy of the type administered here appears to offer little advantage once an initial response has been achieved.

Corynebacterium parvum versus bacille Calmette-Guérin adjuvant immunotherapy of stage II malignant melanoma.

Two separate studies have been reported comparing Corynebacterium parvum and bacille Calmette-Guérin (BCG) as adjuvant immunotherapy for stage II melanoma patients (The Milton S. Hershey Medical Center, 48 patients; Southeastern Cancer Study Group [SECSG], 162 patients). As the criteria for patient selection and drugs used were similar, we have pooled the data to analyze the effects of these two treatments. Both studies used BCG (Tice, Chicago, IL) 3 x 10(8) live organisms per treatment by Tine technique and C parvum (Burroughs-Wellcome, Triangle Park, NC) subcutaneous at a dose of 4 mg/m2 (SECSG) or 5 micrograms/m2 (Hershey) per treatment. The only difference in these studies was the frequency of immunization, with patients in Hershey receiving 22 doses and the SECSG patients receiving 55 doses during the 2-year period of treatment. Kaplan-Meier life-table analysis for the 210 patients shows a prolonged disease-free interval for patients treated with C parvum (P = .02, two-sided Mantel procedure). In similar fashion, patients treated with C parvum had an improved survival rate (from all causes) when compared with BCG-treated patients (P = .012). An analysis of the results for the 170 patients for which the number of positive nodes was available was performed using Cox's model, with nodes as a stratification variable and with covariates of place, treatment, age, and sex. In this analysis, an observed benefit for C parvum on the disease-free interval had a P value of .37 while the benefit of C parvum on the survival times (from all causes) had a P value of .04. When the same analysis was performed using only patients aged younger than 60 years, the observed benefit of C parvum on disease-free interval had a P value of .08 and the benefit of C parvum on survival times (from all causes) had a P value of .008.

Phase III study of BCOP v CHOP in unfavorable categories of malignant lymphoma: a Southeastern Cancer Study Group trial.

A total of 296 evaluable patients with unfavorable categories of malignant lymphoma were randomly assigned treatment with cyclophosphamide, vincristine, and prednisone plus BCNU (BCOP) or doxorubicin (CHOP). In diffuse histiocytic (DH) lymphoma, CHOP produced superior complete (54% v 34%) and total (70% v 46%) response rates. Among the responders to either therapy, no differences were seen in duration of response or survival times. Median duration of response has not been reached with follow-up in excess of 50 months. In categories of lymphoma other than DH (including small-cell, mixed, and nodular histiocytic lymphomas), complete (27% v 29%) and total (48% v 54%) responses were similar for BCOP and CHOP, as were durations of response and survival. These data suggest that BCOP and CHOP are equivalent regimens for other categories of malignant lymphomas. CHOP appears preferable for diffuse large-cell categories, since it resulted in greater overall survival in patients with DH lymphoma; this was due to a significantly greater response rate, since patients with DH lymphoma who did respond to BCOP maintained their response and survived as long as did the CHOP responders.

A phase III trial comparing idarubicin and daunorubicin in combination with cytarabine in acute myelogenous leukemia: a Southeastern Cancer Study Group Study.

PURPOSE: A randomized clinical trial was undertaken to compare the therapeutic effectiveness of idarubicin (IDR) to daunorubicin (DNR), and both were given in combination with cytarabine (CA) in acute myelogenous leukemic (AML) patients. PATIENTS AND METHODS: Newly diagnosed patients were given a daily infusion of CA (100 mg/m2) for 7 days and were assigned randomly to receive DNR (45 mg/m2) or IDR (12 mg/m2) daily for the first 3 days. Those patients who achieved a complete remission (CR) were given three consolidation courses that consisted of CA (100 mg/m2 intravenously [IV]) and thioguanine (TG; 100 mg/m2 orally) every 12 hours for 5 days and either DNR (50 mg/m2) or IDR (15 mg/m2) on the first day of each cycle. After consolidation, patients received late intensification, which consisted of the same drugs used for induction except that the CA was given for 5 days and the anthracycline for 2 days. Four courses were planned at 13-week intervals. RESULTS: The CR rates were 75 of 105 (71%) on the IDR arm and 65 of 113 (58%) on the DNR arm (P = .03). The median survival and median remission durations were 297 and 433 days, respectively, on the IDR arm. The median survival and median remission durations were 277 and 328 days, respectively, on the DNR arm. Six deaths occurred during late intensification, five on IDR and one on DNR; this approach was abandoned after 47 patients were entered. The median survival was significantly longer for patients who received late intensification. CONCLUSION: This trial demonstrated that IDR was more effective than DNR in remission induction in AML.

Randomized comparison of two combination regimens versus minimal chemotherapy in nonsmall-cell lung cancer: a Southeastern Cancer Study Group Trial.

Patients with advanced nonsmall-cell lung cancer (NSCLC), good performance status, and no prior chemotherapy were randomized to receive one of three regimens: intravenous vindesine (V) 3 mg/m2 every 2 weeks; V 3 mg/m2 weekly for 5 weeks, followed by a dose every 2 weeks plus mitomycin (VM) 20 mg/m2 day 1 and then 15 mg/m2 every 6 weeks; or V at the more intensive dose rate plus cisplatin (VC) 120 mg/m2 with forced diuresis on days 1 and 29 and then every 6 weeks. A total of 435 patients were enrolled in the trial, with 410 (94%) assessable for prognostic characteristics and survival. Among the 375 patients assessable for response, only 58 (15%) achieved objective response. Single-agent V every 2 weeks was inactive (response rate less than 1%), effectively acting as a no-treatment arm. Among assessable patients receiving VM, 33 (27%) responded; among patients receiving VC, 24 (19%) responded. There was no statistically significant survival difference among the treatment arms, with median survival among those treated with V 14.8 weeks, VM 20.4 weeks, and VC 24.7 weeks; VC achieved borderline significance (P = .06) compared with V. In a prognostic factor analysis, treatment was not a significant factor (P = .447) for survival. Thus, in this large multicenter trial, neither a high-dose cisplatin combination nor a noncisplatin regimen (VM) with a comparable response rate had a significant survival advantage over minimal chemotherapy. New approaches are needed in advanced NSCLC.

Meta-analysis of chemotherapy versus combined modality treatment trials in Hodgkin's disease. International Database on Hodgkin's Disease Overview Study Group.

DESIGN: To perform a meta-analysis of all randomized trials that compared chemotherapy (CT) alone versus combined modality treatment (CT + radiotherapy [RT]) for which individual patient data could be made available. PATIENTS AND METHODS: Data on 1,740 patients treated on 14 different trials that included 16 relevant comparisons have been analysed. Eight comparisons were designed to evaluate the benefit of additional RT after the same CT (CT1 v CT1 + RT; additional RT design). Eight comparisons were designed to evaluate whether RT in a combined modality setting can be substituted by CT using either more cycles of the same CT or regimens that contain additional drugs (CT1 + CT2 v CT1 + RT or CT1 v CT2 + RT; parallel RT/CT design). RESULTS: Additional RT showed an 11% overall improvement in tumor control rate after 10 years (P = .0001; 95% confidence interval [CI], 4% to 18%). No difference could be detected with respect to overall survival (P = .57; 95% CI, -10% to 4%). In contrast, when combined modality treatment was compared with CT alone in the parallel-design trials, no difference could be detected in tumor control rates (P = .43; 95% CI, -6% to 9%), but overall survival was significantly better after 10 years in the group that did not receive RT (P = .045; 8% difference; 95% CI, 1% to 15%). There were significantly fewer fatal events among patients in continuous complete remission (relative risk [RR], 1.73; 95% CI, 1.17 to 2.53; P = .005) if no RT was given. CONCLUSION: Combined modality treatment in patients with advanced-stage Hodgkin's disease overall has a significantly inferior long-term survival outcome than CT alone if CT is given over an appropriate number of cycles. The role of RT in this setting is limited to specific indications.

Long-term follow-up of a randomized post-induction therapy trial in acute myelogenous leukemia (a Southeastern Cancer Study Group trial).

A phase III clinical trial was designed to determine if more intensive induction and consolidation therapy for acute myeloblastic leukemia increases the remission rate and prolongs survival. A minor objective was to determine if the use of non-cross resistant drugs was more effective than the same drugs used for induction. Patients with untreated leukemia between the ages of 15 and 50 were given daunorubicin 45 mg/m2 for the first 3 days of a 10-day continuous infusion of cytosine arabinoside, initially at a dose of 2000 mg/m2 but reduced to 100 mg/m2 because of toxicity. Those under 36 achieving a complete remission and with an histocompatible donor were assigned to a transplant arm. The rest were randomized to receive one of three consolidation arms: A, cytosine arabinoside, 200 mg/m2 daily for 7 days and daunorubicin 45 mg/m2 daily for 3 days for three courses; B, one course as in Arm A followed by amsacrine, 120 mg/m2 daily for 5 days followed by a 5-day continuous infusion of azacytidine, 150 mg/m2/day; C, thioguanine and cytosine arabinoside, 100 mg/m2 every 12 h and daunorubicin 10 mg/m2 daily for 5 days for three courses followed by four maintenance courses of cytosine arabinoside, 100 mg/m2 daily for 5 days and daunorubicin, 45 mg/m2 for 2 days every 13 weeks. From 1981 to 1986, 398 eligible patients were enrolled and 219 achieved a complete remission. The initial induction dose of cytosine arabinoside was reduced after five of 29 patients exhibited fatal gastrointestinal toxicity. Only 11 patients were assigned to the transplant arm. There were no significant differences in the consolidation arms. The 5 year disease-free survivals were 38, 31 and 27% in arms A, B, and C respectively. Intensive consolidation therapy with the same or different drugs used in induction was as effective as lower dose consolidation followed by maintenance therapy.

A phase III trial of high-dose cytosine arabinoside with or without etoposide in relapsed and refractory acute myelogenous leukemia. A Southeastern Cancer Study Group trial.

A phase III clinical trial was developed to test whether the addition of etoposide to a high-dose cytosine arabinoside regimen would improve the remission rate, duration of remission, and survival in relapsed and refractory patients with acute myelogenous leukemia. One hundred and thirty-one patients stratified by age, performance status, percentage of marrow blasts, platelet count, bilirubin and presence or absence of clinical infection, refractory or relapsed (+/- 9 months) were randomized to receive high-dose cytosine arabinoside, 3 g/m2 every 12 h for 6 days with or without three doses of etoposide, 100 mg/m2 days 7-9. Of 67 patients randomized to cytosine arabinoside alone, 31% obtained a complete remission with a median remission duration of 11.9 months. Of 66 patients randomized to the combination regimen, 38% obtained a complete remission with a median duration of 25 months. None of these differences were statistically significant. Significantly (p = 0.036) longer survival was seen in patients on the combination regimen under the age of 50. There was no difference in overall survival. Six and 8%, respectively, of patients were free of disease at 5 years. The addition of etoposide to a high-dose cytosine arabinoside regimen had at best a marginal effect at the expense of some increase in toxicity.

A longitudinal study of resting energy expenditure relative to body composition during puberty in African American and white children.

BACKGROUND: Body composition and resting energy expenditure (REE) have not been examined longitudinally during puberty. OBJECTIVE: The purpose of this longitudinal study was to examine the influence of pubertal maturation on REE relative to body composition in African American and white children. DESIGN: The study included 92 white and 64 African American children (mean age at baseline: 8.3 and 7.9 y, respectively) from Birmingham, AL. The children had 2-5 annual measurements of fat mass (FM), lean mass (LM), and REE. The Tanner stages of the children ranged from 1 to 5. Mixed-model repeated-measures analyses were used to test the change in REE relative to body composition with increasing Tanner stage among ethnic and sex groups. RESULTS: LM increased from Tanner stage 1 to subsequent stages. FM relative to LM decreased from Tanner stage 1 to stages 3, 4, and 5 but not from stage 1 to stage 2. The African American children had relatively higher limb LM and lower trunk LM than did the white children. REE declined with Tanner stage after adjustment for ethnicity, sex, FM, and LM. This decline was significant from Tanner stage 1 to stages 3, 4, and 5 but not to Tanner stage 2. After adjustment for age, Tanner stage, FM, and LM or LM distribution, REE was significantly higher in white than in African American children (by approximately 250 kJ/d). CONCLUSION: In a large sample of children at various Tanner stages, we found an ethnic difference in REE after adjustment for age, Tanner stage, FM, and LM that was not explained by the difference in LM distribution.

Lipid and insulin concentrations in obese postmenopausal women: separate effects of energy restriction and weight loss.

The separate effects of energy restriction and weight loss on serum lipids were studied in 24 postmenopausal moderately obese women before and after weight loss of greater than 10 kg to normal weight. Fasting serum triglycerides (TGs), total cholesterol (TC), high-density-lipoprotein (HDL) and low-density-lipoprotein (LDL) cholesterol, and insulin were measured at the end of four 10-d in-hospital phases, two before and two after weight loss: phase I, stable weight; phase II, 3350 kJ/d(800 kcal/d), followed by outpatient weight loss; phase III, 3350 kJ/d (800 kcal/d); and phase IV, stable weight. Diet composition and exercise were constant the entire study. Energy-restriction effect was determined by comparing average values in stable-weight phases (I and IV) with low-energy phases (II and III); weight-loss effect was determined by comparing values in obese phases (I and II) with reduced-weight phases (III and IV). Energy restriction lowered TG, TC, LDL cholesterol, the LDL-HDL cholesterol ratio, and insulin and raised HDL cholesterol (all P less than 0.05). Weight loss lowered TG, TC, LDL cholesterol, and insulin (all P less than 0.01) but did not change HDL cholesterol or the LDL-HDL cholesterol ratio. The results suggest that reduction to a weight-steady nonobese state significantly lowers TG, TC, and LDL cholesterol but does not improve HDL cholesterol or the LDL-HDL cholesterol ratio.

Relationship of urinary myelin basic protein-like material with cranial magnetic resonance imaging in advanced multiple sclerosis.

BACKGROUND: A significant correlation exists between disability and the volume of black holes (BHL VOL), defined as hypointense lesions on T1-weighted cranial magnetic resonance imaging. A consistent correlation has also been reported between urinary myelin basic protein-like material (MBPLM) and the transition toward secondary progression (SP) from relapsing-remitting (RR) multiple sclerosis (MS). OBJECTIVE: To improve the management of MS through a noninvasive and cost-effective test for monitoring disease activity or disease status. DESIGN AND METHODS: From 662 patients with MS (86 with RR MS, 259 with SP MS without continued attacks, and 317 with SP MS with continued attacks), 24-hour urine samples were obtained at enrollment in the phase 3 Linomide (roquinimex) drug study. The urine specimens were analyzed for MBPLM and correlated with clinical features and findings on cranial magnetic resonance imaging. RESULTS: Significant but weak correlations existed between urinary MBPLM and BHL VOL in all patients with MS (r = 0.114, P =.003; n = 662), patients with SP MS without attacks (r = 0.185, P =.003; n = 259), and all patients with SP MS (r = 0.122, P =.003; n = 576). No significant correlations were detected in the RR MS group or any of the disease groups or subgroups whose Expanded Disability Status Scale score was 5.0 or lower. In subgroup analysis, the most significant correlation was detected between urinary MBPLM after adjustment for creatinine and BHL VOL in patients with SP MS with an Expanded Disability Status Scale score of 5.5 or higher but without continued relapses (r = 0.417, P<.001; n = 138). CONCLUSIONS: In patients with advanced SP MS, urinary MBPLM may possibly serve as an indicator of failed remission and axonal damage. Urinary MBPLM correlates with disease status in MS, especially the transition of RR MS to SP MS with advancing disability.

Urinary myelin basic protein-like material in patients with multiple sclerosis during interferon beta-1b treatment.

OBJECTIVES: To determine levels of urinary myelin basic protein-like material (MBPLM) in patients with multiple sclerosis (MS) openly treated with interferon beta-1b and to correlate these with clinical changes. BACKGROUND: Levels of urinary MBPLM correlate with the presence of the progressive phase of MS and with the disease burden detected on T2-weighted, cranial magnetic resonance imaging. Measurement of urinary MBPLM level may be a feasible test for monitoring or predicting response to therapeutic measures. DESIGN AND METHODS: In a prospective study at one site, 166 patients with MS (131 with relapsing-remitting [RR] and 35 with secondary progressive [SP] disease) were treated for a minimum of 1 year and up to 3 years with interferon beta-1b and underwent assessment for neurologic disability (Expanded Disability Status Scale and Scripps Neurological Rating Scale) and change in disease subtype. Urine samples were obtained at 1219 of 1378 clinic visits, and urinary MBPLM level was determined and related to creatinine level to adjust for renal function. RESULTS: Statistical analysis using the general linear models procedure confirmed previous findings that the level of urinary MBPLM related to urinary creatinine level (MBPLM/creatinine) was higher (P<.001) in patients with SP than RR MS. Of the 131 patients with RR MS, SP disease developed in 13 during the observation period. Compared with those in the RR group, the RR to SP group had a higher level (P<.001) of urinary MBPLM and did not differ from the SP group. CONCLUSIONS: The level of urinary MBPLM is higher in SP MS than RR MS but not in RR MS that converts to SP MS. Level of urinary MBPLM may permit the examination of treatment tested to prevent RR disease from becoming progressive.

Postsurgical adjuvant chemotherapy with or without radiotherapy in women with breast cancer and positive axillary nodes: a South-Eastern Cancer Study Group (SEG) Trial.

In a prospective study of 622 women with breast cancer, those with one to three histologically positive axillary lymph nodes were randomised after mastectomy to receive cyclophosphamide 100 mg/m2 orally on days 1-14, methotrexate 40 mg/m2 intravenously on days 1 and 8, and fluorouracil 600 mg/m2 intravenously on days 1 and 8 every 28 days for six cycles (CMF x six), or for twelve cycles of the same chemotherapy (CMF x 12). Those with > or = four positive nodes were randomised to one of these two groups or to 5000 cGy of postmastectomy regional radiotherapy (RT) followed by six cycles of the same chemotherapy (RT + CMF x six). With about 10 years median follow-up, there was no significant difference in survival or disease-free survival among the three groups. There was evidence of decreased locoregional recurrence in patients with > or = four nodes who received RT + CMF x six (relative risk 0.53, P = 0.067). Multivariate analysis indicated that the presence of > or = four positive nodes (negatively) and the percentage of ideal (full) dose of CMF received (positively) were the strongest factors predictive of survival. This study shows no advantage for 12 over six cycles of CMF chemotherapy in women with breast cancer and positive axillary nodes. There was a suggestion of decreased locoregional recurrence but no improvement in survival with radiotherapy for women with > or = four positive nodes.

Ferromagnetic thermoseeds: suitable for an afterloading interstitial implant.

Previous studies have shown implantable ferromagnetic thermoseeds to be a promising hyperthermia method. However, migration from the implant site and chemical toxicity caused by corrosion of the thermoseed alloy have proven to be potential hazards. These problems could be overcome by placing the thermoseeds into removable catheters similar to those used for afterloading interstitial brachytherapy. As an additional merit, the method would allow convenient combination of heat and radiation therapy. To test the clinical performance of this method, we compared temperature distributions and biologic effects in canine muscle and transmissible venereal tumors for bare thermoseeds and thermoseeds contained within catheters. We found no significant difference in the heating patterns and similar tissue changes when all implants were removed immediately after heating. More severe tissue changes were present around bare thermoseeds that were retained. This suggests that catheters provide a safe and reliable method for thermoseed hyperthermia which would allow convenient combination with interstitial radiation.

Southeastern Cancer Study Group: breast cancer studies 1972-1982.

During the past 10 years, the Southeastern Cancer Study Group (SECSG) has been engaged in one major adjuvant study and three major advanced disease studies for patients with adenocarcinoma of the breast. The adjuvant study is demonstrating that six months of adjuvant CMF is the therapeutic equivalent of 12 months and that post-operative irradiation is of no added therapeutic benefit. In patients with advanced disease, a low dose 5 drug combination of CMFVP induces more objective responses than single agent 5FU, but improves survival only for those patients with liver metastases when compared to the sequential use of the same 5 single agents. The three drug combination, CAF, utilizing doxorubicin, induces more objective responses than low dose CMFVP, but it does not improve overall survival. The subsets of patients with bone-only metastases, with local chest wall recurrence and with nodular lung metastases benefit from CAF in terms of a longer duration of disease control and longer duration of unmaintained remission, but have only a marginal improvement in survival. The addition of a phase active combination, CAMELEON, (i.e., sequentially alternating therapy) to CAF has not improved the duration of disease control and survival for patients with liver metastases, lymphangitic and nodular lung metastases compared to CAF. Aggressive combination chemotherapeutic approaches to patients with advanced disease provide better and longer disease and tumor control but only marginal improvements in overall survival. Adding additional agents to a maximally tolerable regimen has not improved the therapeutic outcome.

Cytologic characterization of pulmonary alveolar macrophages by enzyme histochemistry in plastic.

Quantitative morphometric analyses of macrophages should facilitate a more precise definition of the role of macrophages in neoplastic diseases and inflammatory diseases of lymphoid and hemopoietic tissues. The usefulness of the available phenotypic markers is affected by the extent to which they are expressed by macrophages in tissue sections. For our study of phenotypic markers for macrophages in human tissue sections, we selected lung, since pulmonary alveolar macrophages are more readily identified morphologically in tissue sections than macrophages in most other tissues. In 1-2 micron sections of freshly fixed lung embedded in methacrylate, 89.7% of pulmonary alveolar macrophages had histochemically demonstrable acid phosphatase; 86.2%, nonspecific esterase with naphthol ASD chloroacetate as the substrate; 86.2%, nonspecific esterase with alpha-naphthyl butyrate as the substrate; 80.5%, peroxidase; and 75.8%, iron. With respect to their expression of markers, the observed heterogeneity among pulmonary alveolar macrophages is interesting; this heterogeneity may reflect the degree to which they have been activated, the different periods of time since they arrived in the lung, and differences in their local environments. Except for peroxidase, all examined markers were as well demonstrated when tissues were fixed after storage over liquid nitrogen as when fixation was carried out with fresh tissue. Acid phosphatase and nonspecific esterase with the chloroactetate substrate gave bright colors that would facilitate morphometric analyses. The storage of tissue over liquid nitrogen will be equally satisfactory for the characterization of macrophages with histochemical markers and monoclonal antibodies.

Age-related variability in the use of cardiovascular imaging procedures.

OBJECTIVE: To determine if older patients undergo fewer cardiovascular imaging procedures (CIPs) than younger patients when admitted to a tertiary care academic medical center for an acute myocardial infarction (MI), after adjusting for disease severity and comorbidities. DESIGN: Non-current prospective cohort study. SETTING: Urban tertiary care academic medical center. PATIENTS: Medical records of 294 patients admitted and diagnosed with an acute MI between January 1990 and April 1991 were reviewed. MEASUREMENTS: The total number of different CIPs performed during hospitalization was determined. Cardiac catheterizations, echocardiograms, radionuclide ventriculograms, and thallium scans counted as CIPs. Disease severity was assessed by the Acute Physiology Score (APS) of APACHE II, admission Killip's Classification, and peak creatine phosphokinase (CPK) levels. Comorbidities were assessed using a modified Comorbidity Damage Index of Charlson. RESULTS: The mean (+/- SD) number of different CIPs performed during hospitalization was significantly less for those > or = 75 years old (1.3 +/- 1.0) than for those < 75 years old (1.7 +/- 1.0) (P = 0.01), and CIP number negatively correlated with age (Spearman r = -0.178; P = 0.01). Mean CIP number decreased from 2.0 +/- 1.1 for those < 45 years old to 0.9 +/- 0.6 for those > or = 85 years old (P = 0.02). Other factors positively associated (P < 0.10) with CIP number were: CPK values in the highest quartile of the study population (> 355 U/L); admission to a cardiology, medical, or family practice service; no CIP performed at an outside hospital prior to transfer; admission Killip's Classification of less than IV, and a Q-wave MI. After adjusting for these variables in a multiple regression model, age > or = 75 remained an independent predictor of decreased CIP use (P = 0.003). The modified comorbidity index score and the APS score, a general measure of severity of illness, were not significantly associated with CIP use. When procedures were examined individually, no significant age-related differences were noted in the use of thallium scans, radionuclide ventriculograms, or echocardiograms. Older patients did, however, remain less likely to undergo cardiac catheterizations (P < 0.001). CONCLUSION: Older patients, regardless of underlying disease severity or comorbidities, undergo fewer invasive cardiovascular evaluations than younger patients when admitted to a tertiary care academic medical center for an acute MI.

Ineffectiveness of adjuvant chemotherapy using DTIC and cyclophosphamide in patients with resectable metastatic melanoma.

A randomized, prospective trial of adjuvant chemoimmunotherapy was compared in a group of 136 patients with melanoma after complete surgical resection of advanced regional metastasis (stage III) or isolated distant metastasis (stage IV). All patients received a 2-year course of nonspecific adjuvant immunotherapy of subcutaneous injections of Corynebacterium parvum (4 mg/m2 divided among the four extremities in 1- to 2-week cycles). Half of the patients also received a 6-month course of dimethyl triazeno imidazole carboxamide (DTIC) plus cyclophosphamide chemotherapy (each at 600 mg/m2 administered intravenously every 3 weeks for nine cycles) while the other half received no chemotherapy. Analysis of the data showed that adjuvant chemotherapy did not provide any demonstrable therapeutic effect, either in terms of disease-free survival or overall survival. No benefit was observed in subgroups of patients categorized by disease stage, site of metastasis, or sex. The drugs did cause a substantial rate of morbidity, however, since 42% of the patients had severe nausea and vomiting, while 13% had hair loss. The C. parvum was well tolerated in almost all patients. This is a particularly high-risk group for subsequent metastases since only 24% of the patients were free of disease for 1 year and 12% after 2 years. Adjuvant DTIC and cyclophosphamide had no observable therapeutic effect on this population of high-risk patients with melanoma.