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Can older cancer patients tolerate chemotherapy? A prospective pilot study.

BACKGROUND: To the authors' knowledge, few data currently are available regarding the tolerance to chemotherapy in older cancer patients. This prospective pilot study evaluated the changes in functional, mental, nutritional, and comorbid status, as well as the quality of life (QOL), in geriatric oncology patients receiving chemotherapy. METHODS: Sixty patients age > or = 70 years who were undergoing cancer chemotherapy were recruited in a university-based comprehensive cancer center. Changes in physical function were measured by the Eastern Cooperative Oncology Group performance status (ECOG PS) and Instrumental Activities of Daily Living (IADLs), mental health changes were measured by the Mini-Mental State Examination and the Geriatric Depression Scale (GDS), comorbidity was measured by Charlson's index and the Cumulative Illness Rating Scale-Geriatric, nutrition was measured by the Mini-Nutritional Assessment, and QOL was measured by the Functional Assessment of Cancer Therapy-General (FACT-G). Changes were assessed at baseline and at the end of treatment (EOT). Grade 4 hematologic and Grade 3-4 nonhematologic toxicities were recorded. RESULTS: Thirty-seven patients (63%) completed both assessments. Older cancer patients demonstrated a significant decline in measurements of physical function after receiving chemotherapy, as indicated by changes in scores on the IADL (P = 0.04) and on the physical (P = 0.01) and functional (P = 0.03) subscales of the FACT-G. They also displayed worse scores on the GDS administered postchemotherapy (P < 0.01). Patients who experienced severe chemotoxicity had more significant declines in ECOG PS (P = 0.03), IADL (P = 0.03), and GDS (P = 0.04), and more gain in the social well-being subscale (P = 0.02) of the FACT-G, than those who did not experience severe chemotoxicity. However, changes in most scores were small in magnitude clinically. No significant change was found between baseline and EOT in nutrition, comorbidity, and other aspects of the FACT-G. CONCLUSIONS: Older cancer patients undergoing chemotherapy may experience toxicity but generally can tolerate it with limited impact on independence, comorbidity, and QOL levels. It is important to recognize and monitor these changes during geriatric oncology treatment.

Activities of Daily Living↗

Chinese version of the M. D. Anderson Symptom Inventory: validation and application of symptom measurement in cancer patients.

BACKGROUND: Symptom management is an essential component of cancer treatment for patients of every culture and nationality. Symptom assessment depends on subjective reporting, mandating linguistically equivalent versions of symptom assessment scales. Because disease-related and treatment-related symptoms most often occur in clusters, there is a global need for a standardized multiple-symptom assessment tool. METHODS: The authors sought to validate the Chinese version of the M. D. Anderson Symptom Inventory (MDASI-C) by enrolling patients who had received various diagnoses of and different types of treatment for cancer (n = 249) in a cross-sectional symptom study conducted at an urban cancer center in China. RESULTS: Factor analysis identified 2 underlying constructs, general symptoms and gastrointestinal symptoms, which had Cronbach alpha coefficients of 0.86 and 0.84, respectively. These results were consistent with English- and Japanese-language MDASI validation studies. Known-group validity was supported by the MDASI-C's ability to detect significant differences in symptom and interference levels according to Eastern Cooperative Oncology Group performance status (ECOG PS; P < 0.001) and chemotherapy status (P < 0.05). Fifty-five percent of the study cohort had > or = 1 symptom that was considered severe (score > or = 7 on a 0-10 scale). ECOG PS was strongly associated with symptom burden (total interference score: R(2) = 0.26; P < 0.001). Fatigue, sadness, drowsiness, and lack of appetite accounted for most of the variability in the total interference score (R(2) = 0.49; P < 0.05). CONCLUSIONS: The authors demonstrated that the MDASI-C is a valid, reliable, and concise tool for measuring symptom severity and interference with functioning in Chinese cancer patients.

Adolescent↗

Epoetin alfa improves quality of life in patients with cancer: results of metaanalysis.

BACKGROUND: Anemia in patients with cancer causes fatigue, weakness, and impaired concentration, negatively impacting quality of life (QOL). In clinical trials involving patients with cancer who had varied characteristics, it has been shown that epoetin alfa treatment increased hemoglobin levels and improved QOL. A systematic review and metaanalysis of data from those trials was conducted to summarize existing knowledge on the role of epoetin alfa in improving QOL for anemic patients with cancer. METHODS: The Cochrane Library and other data bases were searched for published and unpublished, randomized/controlled and single-arm studies that included > or = 20 patients with cancer per arm, epoetin alfa treatment, and QOL assessment by Cancer Linear Assessment Score (CLAS), Functional Assessment of Cancer Therapy (FACT) scale, Eastern Cooperative Oncology Group (ECOG) scale, and/or Medical Outcomes Study Short-Form 36 (SF-36) scale. RESULTS: Among 11,459 patients from 23 trials, epoetin alfa and control cohorts were indistinguishable (with regard to demographic, clinical, QOL variables) at baseline. Epoetin alfa improved CLAS (20-25%), FACT-Fatigue (17%), and FACT-Anemia (12%) scores (P = 0.05). ECOG scores worsened for control cohorts (P = 0.05); epoetin alfa cohorts remained unchanged. Four of the SF-36 subscales, Physical Function, Role Physical, Vitality, and Social Function, improved with epoetin alfa (P = 0.05). Results adjusted for confounding factors remained consistent. CONCLUSIONS: This metaanalysis confirmed that epoetin alfa improves QOL significantly in patients with cancer, emphasizing the need to manage anemia in this population.

Anemia↗

A Phase II study of gemcitabine and cisplatin in advanced biliary tract cancer.

BACKGROUND: The authors performed a Phase II study of combination chemotherapy with gemcitabine and cisplatin in patients with inoperable biliary tract cancer to evaluate efficacy and toxicity of this combination. In addition, the correlation between the CA 19-9 response and clinical outcome was analyzed. METHODS: The eligibility criteria for this study were 1) histologically or cytologically confirmed inoperable biliary tract cancer in patients with metastatic or recurrent disease; 2) age between 18 and 70 years; 3) at least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria; 4) an Eastern Cooperative Oncology Group (ECOG) performance status < or = 2; 5) a life expectancy of at least 3 mos; and 6) adequate bone marrow, hepatic, and renal function. The patients received gemcitabine (1250 mg/m(2), Days 1 and 8) and cisplatin (60 mg/m(2), Day 1) every 3 weeks. Tumor response was assessed by RECIST criteria every 2 cycles of chemotherapy. Treatment was continued until progression of disease was documented. RESULTS: Twenty-nine patients were enrolled. The median age of these patients was 52 years (range, 37 to 69 yrs), and the median ECOG performance status was 1. No complete response was observed, and 10 of 29 patients had partial responses. The overall response rate was 34.5% (95% confidence interval [CI], 17.9-54.3) for the intent-to-treat analysis. Stable disease was observed in 4 (13.8%) patients and progressive disease in 13 (44.8%) patients. The median follow-up time was 10.0 months (95% CI, 7.2-12.8). The median time to progression (TTP) was 3.0 months (95% CI, 2.12-3.88), and the median overall survival was 11 months (95% CI, 5.49-16.5). Although these results showed a better response rate (57.1 % vs. 27.3%) and survival (12 vs. 10 mos) in patients with a decline in CA 19-9 of at least 25%, these data were statistically not significant. In addition, there was a significant positive correlation between the increment in CA 19-9 values and tumor progression as determined with RECIST criteria (r = 0.96, P < 0.01). However, there was no definite correlation between the CA 19-9 response and the response according to RECIST criteria (P = 0.087). National Cancer Institute (NCI) common toxicity criteria (CTC) Grade 3 or 4 hematologic toxicities included neutropenia in 4 (14%) patients and anemia in 1 (3%) patient. Two of 4 patients with Grade 3 or 4 neutropenia had febrile episodes (7%) and required hospital admissions. NCI-CTC Grade 3 or 4 nonhematologic toxicity included nausea in 1 (3%) patient. There were no treatment-related deaths. CONCLUSION: The combination chemotherapy with gemcitabine and cisplatin in inoperable biliary tract cancer was tolerable for most patients and showed modest response rates. The role of CA 19-9 monitoring as a surrogate biomarker in patients with BTC treated with gemcitabine chemotherapy should be further investigated.

Adenocarcinoma↗

Phase II study of mitoxantrone and ketoconazole for hormone-refractory prostate cancer.

BACKGROUND: Doxorubicin plus ketoconazole has exhibited significant activity in patients with advanced prostate cancer. However, overall and cardiac-specific toxicity was reported to be high. Mitoxantrone has activity similar to that of doxorubicin, is less cardiotoxic, and is widely used to treat prostate cancer. The current study sought to evaluate the toxicity and activity of mitoxantrone plus ketoconazole in a cohort of patients with hormone-refractory prostate cancer. METHODS: Progression after medical or surgical castration and, for those patients receiving antiandrogens, progression after withdrawal was required, as was objective evidence of metastasis, castrate levels of testosterone, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, and intact cardiac function. After enrollment onto a multicenter local consortium study, subjects were treated with mitoxantrone at a dose of 12 mg/m2 intravenously every 3 weeks plus continuous oral ketoconazole at a dose of 400 mg 3 times daily and ascorbic acid at a dose of 250 mg. Replacement doses of hydrocortisone were given. RESULTS: For 40 enrolled subjects, the median prostate-specific antigen and ECOG performance status were 68 and 1, respectively, 53% had Gleason scores of 8 to 10, and all had metastasis. Predominant Grade 3/4 toxicities were: neutropenia in 13%, neutropenic fever in 10%, and anemia in 13%. Of 37 evaluable patients, 8% achieved a complete remission (CR) and 62% achieved a partial remission (PR), for a CR plus PR rate of 70%. For soft tissue and bone disease, overall response rates were 13% and 8%, respectively. The median progression-free survival and overall survival were 10 months and 18 months, respectively. CONCLUSIONS: Mitoxantrone plus ketoconazole is well tolerated, is active in hormone-refractory prostate cancer, and should be studied further.

Aged↗

Smoking affects treatment outcome in patients with advanced nonsmall cell lung cancer.

BACKGROUND: The purpose of the current study was to determine whether smoking during chemotherapy or chemoradiation therapy for nonsmall cell lung cancer (NSCLC) affects treatment outcome. METHODS: The authors reviewed the medical records of patients with NSCLC (AJCC Stage III or IV) who were treated with frontline chemotherapy or chemoradiation therapy at the University of Texas M. D. Anderson Cancer Center between January 1993 and December 2002. Treatment type, response, progression-free survival, and overall survival (OS) were correlated with patient demographic characteristics, clinical features, and smoking habits at the time of diagnosis and during therapy. RESULTS: Of 1370 patients who were eligible for analysis, 497 received chemoradiation therapy and 873 received chemotherapy. In the chemoradiation group, 6% of patients were never-smokers, 45% were former smokers, and 49% were current smokers. Multivariate analysis demonstrated no prognostic effect of smoking status on treatment response or OS rates in the chemoradiation therapy group. In the chemotherapy group, 16% of patients were never-smokers, 42% were former smokers, and 42% were current smokers; 20% of patients continued to smoke during therapy. Never-smokers had higher response rates (19% vs. 8% vs. 12%; P=.004) and lower rates of progressive disease (49% vs. 65% vs. 66%; P=.002) than former and current smokers, respectively. The OS rates were found to be higher among never-smokers (P<0001), women (P=.002), and those with a better Eastern Cooperative Oncology Group (ECOG) performance status (P<.0001). The multivariate Cox model indicated that with adjustment for age, gender, stage of disease, and ECOG performance status, the hazard ratio was 1.47 for former smokers (P=.003) and 1.55 for current smokers (P=.0004). Active smoking during therapy did not appear to impact outcome. CONCLUSIONS: Never-smokers were found to have an improved outcome over smokers when treated with chemotherapy.

Adolescent↗

A phase II study of irinotecan plus cisplatin for patients with advanced stage IIIB or IV NSCLC previously treated with nonplatinum-based chemotherapy.

BACKGROUND: Irinotecan (1) and cisplatin (P) are active chemotherapy agents with clinical synergy in non-small-cell lung cancer (NSCLC). We evaluated the efficacy of IP regimen as a salvage treatment of patients with NSCLC that progressed after nonplatinum-containing regimen(s). METHODS: Eligibility required histologically confirmed NSCLC, bidimensionally measurable disease, ECOG PS 0-2, and progressive disease after nonplatinum-based chemotherapy. Treatment consisted of I (65 mg/m2) and P (30 mg/m2) i.v. on Days 1 and 8 of a 21-day cycle, for a maximum of 6 cycles. An informed consent was obtained from all patients. RESULTS: Between August 2002 and May 2004, 32 patients with median age of 56 years (range, 42-74) were enrolled. Twenty-four (75%) patients were men, and 28 (88%) had ECOG PS 0 or 1. Twenty-five patients had adenocarcinoma and 6 had squamous-cell carcinoma. All patients were evaluated for response and toxicity, and the response rate was 40.6%. After a median follow-up of 18.5 months, the median survival time was found to be 9.3 months, with a 1-year survival rate of 43.8%. Toxicities were moderate and manageable, with 47% G3 and 9% G4 neutropenia, 19% G3 diarrhea, and 22% G3 asthenia. There was no G4 nonhematologic toxicity. CONCLUSIONS: The irinotecan and cisplatin combination is an active and well-tolerated regimen for the patients with advanced NSCLC that progressed after nonplatinum-containing regimen(s).

Adenocarcinoma↗

An alternating chemotherapy combination (MACOBLE) for intermediate and high-grade non-Hodgkin's lymphoma.

From June 1983 to February 1986, 48 patients with intermediate or high-grade non-Hodgkin's lymphomas (NHL) received a CHOP based combination with the addition of etoposide on days 1 and 2, bleomycin days 1 and 10 and methotrexate 1.5 g/m2 on day 10 (MACOBLE). Their median age was 59 years, 20 (42 per cent) had an ECOG performance status (PS) of 2 or 3, 24 (50 per cent) had stage IV disease, 25 (52 per cent) B symptoms and 21 (44 per cent) bulk (greater than 10 cm) disease. With a median follow-up of 62 months, 12 patients are alive, 10 of whom are disease-free. Median overall survival was 13 months (95 per cent confidence interval 6-23 months) with actuarial 5-year survival of 25 per cent (95 per cent confidence interval 13-37 per cent). Factors associated with inferior survival were ECOG PS 2 or 3 (P = 0.004), B symptoms (P = 0.013) and bulk disease (P = 0.017). These data suggest that, when treating an unselected patient population, attempts to increase the intensity of first-line chemotherapy may not improve the outcome.

Adult↗

Gallbladder adenocarcinoma: prognostic significance of tumor acid mucopolysaccharide content.

The gall bladder mucosa is composed of neutral mucopolysaccharide and protein radical containing secretory cells, protein radical containing migratory cells, and neutral and acid mucopolysaccharides plus sialic acid containing goblet cells. The prognostic significance of histologic or histochemical parameters in gall bladder adenocarcinoma (GBA) are unknown. To determine if histochemical acid mucopolysaccharide content in GBA has prognostic value, GBA histologic sections from 26 advanced stage disease patients participating in Eastern Cooperative Oncology Group (ECOG) treatment study EST-2273 were stained with alcian blue at pH. 1.0, assessed by a pathology panel for either high (greater than 50%) or low (less than 50%) acid mucopolysaccharide content, and correlated with patient survival. Initial panel unanimous concurrence rate on acid mucopolysaccharide content was 88.9%. Median survival times from the start of chemotherapy to date of death for high acid mucopolysaccharide content GBA was 14 weeks versus five weeks for the low content GBA (P less than 0.0001). The results indicate that high acid mucopolysaccharide content in GBA significantly improves prognosis. ECOG recommends stratification by acid mucopolysaccharide content in future GBA treatment investigations.

Adenocarcinoma↗

Gallbladder adenocarcinoma: the prognostic significance of histologic grade.

Gallbladder adenocarcinoma (GBA) postresection 5-year survival rates are less than 5%, but when histologically confined to the mucosa or submucosa, survival rates of 64% (5 years) and 44% (10 years) have been reported. Whether any other histologic features of GBA have prognostic significance is unknown. This investigation was conducted to determine if GBA histologic grade correlates with survival. Thirty patients with advanced stage GBA participating in Eastern Cooperative Oncology Group (ECOG) treatment protocol EST-2273 served as the study material. Using glandular tumor grade criteria recommended by others, a panel of 7 ECOG pathologists categorized the GBA as either predominantly low or high histologic grade. Each patient's GBA histologic section measured no less than 1.0 X 1.0 cm. Predominant grade was defined as being that grade present in greater than 75% of the histologic section. Patient survival times by grade were calculated from date of initiation of chemotherapy until date of death. The 13-week low grade GBA patient survival was significantly longer than the 7-week high grade GBA patient survival (p less than 0.01). Stratification of patients by either high or low predominant histologic grade is recommended in future GBA treatment studies.

Adenocarcinoma↗

The role of physical and psychological symptoms in desire for death: a study of terminally ill cancer patients.

The current study assessed the attitudes of the desire for hastened death in terminally ill cancer patients and whether these are determined by their physical and psychological symptoms. The final sample consisted of 106 terminally ill cancer patients attending a Palliative Care Unit, in University of Athens, Greece, between June and October 2004. Significant associations were found between the desire for hastened death (D.H.D.) and 'pain' (r=0.469, p<0.005), 'fatigue' (r=0.591, p<0.0005), 'loss of appetite' (r=0.622, p<0.0005) and 'feeling sad' (r=0.635, p<0.0005). Statistically significant associations were also found between Schedule of Attitudes towards Hastened Death (SAHD) scores, age (r=0.300, p=0.002) and ECOG (p<0.0005). Twenty-six percent of the patients reported high D.H.D. while 41% reported moderate desire. In the prediction of SHAD the contribution of 'pain' (p=0.011), 'lack of appetite' (p=0.012) and 'sadness' (p=0.011) is high (42% of variance). Further findings suggest that D.H.D. is significantly related to 'feeling sad', 'lack of appetite', 'pain' and 'fatigue' after controlling for age, gender and performance status according to ECOG in terminally ill cancer patients.

Adult↗

Validation of the Distress Thermometer with bone marrow transplant patients.

The Distress Thermometer (DT) is a one-item screening measure of psychological distress in cancer patients. This study examines the operating characteristics of the DT in patients about to undergo bone marrow transplant (BMT). Patients (N=491) completed the DT, the Center for Epidemiological Studies-Depression Scale (CES-D), the State-Trait Anxiety Inventory-State Version (STAI-S), the ECOG Performance Status Scale, and the Patient Problem List. DT scores were related to higher depression, higher anxiety, and poorer performance status. Receiver operating characteristic (ROC) curve analyses of DT scores yielded area under the curve estimates of 0.75 when compared to the CES-D cutoff score of 16, suggesting the DT has acceptable overall accuracy. The DT cutoff score of 4 had the greatest sensitivity and specificity when compared to the CES-D cutoff score. Patients above this cutoff score reported worse ECOG scores and more practical, family, emotional, and physical problems (all p's< or =0.05) than those below the cutoff. The findings suggest the DT is a useful tool for screening for distress in BMT patients. The optimal DT cutoff score of 4 found here was identical to that found in another study using different criteria. This cutoff score also identified patients with problems likely to reflect psychological distress.

Adult↗

Seizures and hippocampal damage produced by dendrotoxin-K in rats is prevented by the 21-aminosteroid U-74389G.

The epileptogenic and neurodegenerative effects of dendrotoxin K (DTx-K), from Dendroaspis polylepsis, a specific blocker of a noninactivating, voltage-sensitive K+ channel, were studied after focal injection into one dorsal hippocampus in rats pretreated with the 21-aminosteriod U-74389G, a scavenger of free oxygen radicals. Administration of 35 pmol DTx-K elicited in all of the treated animals (n = 6) motor seizures and bilateral electrocortical (ECoG) discharges after a latent period of approximately 5 min. At 24 h, histological examination of brain (n = 6) coronal sections (10 microns; n = 6 per brain) detected bilateral damage to the hippocampal formation. Quantitation of damage revealed significant bilateral neuronal cell loss in the CA1 and CA4 pyramidal cell layer and dentate gyrus granule cell layer relative to the corresponding brain regions of rats (n = 6) injected with bovine serum albumin (300 ng), which per se was ineffective in all respects. DTx-K (35 pmol) also caused a significant loss of CA3 pyramidal neurons ipsilateral to the site of toxin injection. Systemic (i.p.) administration of U-74389G (5 mg/kg given 30 min beforehand) delayed the onset of motor and ECoG seizures and reduced the number of epileptogenic discharges typically observed in rats receiving an injection of DTx-K (35 pmol) alone. Similarly, this treatment prevented the damage inflicted to the hippocampus by the toxin and in no instance was significant neuronal loss observed. At variance with these results, pretreatment with U-74389G (up to 10 mg/kg i.p.) failed to prevent seizures and CA1 hippocampal damage evoked by intra-hippocampal injection of alpha-DTx (35 pmol), a DTx-K homologue which preferentially inhibits a slowly inactivating, voltage-dependent K+ conductance in nerve cells. In conclusion, the present data support a role for free oxygen radicals in mediating hippocampal damage induced by DTx-K, but not alpha-DTx, and confirm the original deduction that these DTx homologues are complementary neurobiological tools to study mechanisms of seizures and neuronal death.

Animals↗

4-Aminopyridine reverses saxitoxin (STX)- and tetrodotoxin (TTX)-induced cardiorespiratory depression in chronically instrumented guinea pigs.

The extent to which cardiorespiratory infirmity and other sublethal effects of saxitoxin (STX) and tetrodotoxin (TTX) can be reversed by 4-aminopyridine (4-AP) was investigated in guinea pigs chronically instrumented for the concurrent electrophysiological recordings of electrocorticogram (ECoG), diaphragmatic electromyogram (DEMG), Lead II electrocardiogram, and neck skeletal muscle electromyogram. Animals were intoxicated with either STX or TTX (2 and 3 microg/kg, im) to produce a state of progressive cardiorespiratory depression (depicted by decreasing DEMG amplitude, bradypnea, and bradycardia). At the point where cardiorespiratory performance was most seriously compromised (approximately 30 min posttoxin), 4-AP (1 or 2 mg/kg, im) was administered. The therapeutic effect of 4-AP was striking in that, within minutes, the toxin-induced diaphragmatic blockade, bradypnea, bradycardia, and depressed cortical activity were all restored to a level either comparable to, or surpassing, that of control. The optimal 4-AP dose level was determined to be 2 mg/kg (im) based on analyses of cardiorespiratory activity profiles throughout the course of intoxication and 4-AP treatment. At the dose levels (either 1 or 2 mg/kg) used to restore ventilatory function and cardiovascular performance, 4-AP produced no sign of seizures and convulsions. Although less serious secondary effects such as cortical excitant/arousal effect (indicated by ECoG power spectral analysis) and transient periods of skeletal muscle fasciculation were observed, these events were of minor concern particularly in view of the remarkable therapeutic effects of 4-AP.

4-Aminopyridine↗

Reversal of saxitoxin-induced cardiorespiratory failure by a burro-raised alpha-STX antibody and oxygen therapy.

Reversal of saxitoxin (STX; 10 micrograms/kg, ip) induced cardiorespiratory effects by oxygen ventilation and burro-raised alpha-STX antitoxin (60 mg/kg, i.v.) was studied in urethane-anesthetized guinea pigs acutely instrumented for concurrent monitoring of medullary respiratory-related single units, diaphragm EMG, Lead II electrocardiogram, arterial blood pressure (BP), arterial pH, and O2/CO2 tensions, electrocorticogram (ECoG), and end-tidal CO2. STX-induced cardiorespiratory effects included (1) a state of progressive bradypnea and hypercapnia; (2) a functional blockade of the diaphragm; (3) a prolongation of respiratory cycle duration; (4) an aberrant bulbar respiratory-related neuronal activity pattern; and (5) a decline in BP and heart rate. The therapeutic effect of artificial ventilation following STX-induced apnea was equivocal in that the cardiorespiratory activities, be they of central or peripheral nature, remained dysfunctional despite continued oxygen ventilation. Spontaneous breathing and cardiovascular performance following STX-induced apnea could all be promptly restored (typically in less than a minute) by combined oxygen/antitoxin therapy. Notable also was a state of uncompensated acidemia (as revealed by changes in arterial pH and CO2 tension) which persisted throughout the course of therapeutic intervention. Notwithstanding, the ventilatory frequency continued to be low, the central respiratory activity pattern remained aberrant, and the ECoG amplitudes were still depressed. In consideration of these findings, and of the large molecular weight of alpha-STX antitoxin (> 150,000 Da) which limits its entry into the CNS, we are of the opinion that the therapeutic effects of antitoxin are probably confined primarily to the periphery.

Adrenal Glands↗

Brain viability and function analyzer: multiparametric real-time monitoring in neurosurgical patients.

We have developed the Brain Viability (BVA) and Brain Function (BFA) Analyzers for monitoring the following parameters from the human cerebral cortex cerebral blood flow: (CBF), NADH redox state, Electro corticography (ECoG), brain temperature, extracellular K+, DC potential and intracranial pressure (ICP). The BVA monitors the first 4 parameters only. The Brain viability probe (BVP) and Brain function multiprobe (BFM) were used during 11 operations and in 18 ICU patients, respectively. Preliminary results from the OR showed that 5 patients exhibited a typical increase in CBF in response to changes in end-tidal CO2 without a significant change in the NADH redox state. In 4 other patients no changes in CBF and NADH were observed. Two patients exhibited a "steeling response", i.e., a decrease in CBF and an increase in NADH. In 18 comatose patients monitored in the ICU, the ICP, CBF and ECoG were measured correctly in most patients, whereas NADH and K+ were more problematic. One patient exhibited a typical response, may be due to repeated cortical spreading depression cycles and an ischemic depolarization event. Continuous realtime multiparametric monitoring in neurosurgical patients is feasible and practical in the OR and the ICU. The information provided could be used as a diagnostic tool to guide the procedures or treatment given to the patients.

Body Temperature↗

A phase II study of dihydroxyanthracenedione (DHAD, mitoxantrone, NSC 301739) in advanced malignant melanoma.

The Eastern Cooperative Oncology Group (ECOG) conducted a phase II trial of Dihydroxyanthracenedione (DHAD, Mitoxantrone, NSC 301739) in 28 patients with advanced malignant melanoma, none of whom had received prior cytotoxic chemotherapy. 27 of 28 patients were ECOG performance status 0 or 1. Mitoxantrone was administered at a dose of 12 mg/M2 as a 30-45 minute intravenous infusion repeated every 3 weeks as toxicity and response permitted. Dose limiting toxicity was myelosuppression. No cardiotoxicity was encountered in this study. In this optimal group of patients, only one partial response to Mitoxantrone was observed. At this dose and schedule, Mitoxantrone has no clinically worthwhile activity against malignant melanomas.

Anthraquinones↗

Phase II evaluation of dibromodulcitol and actinomycin D, hydroxyurea, and cyclophosphamide in previously untreated patients with malignant melanoma.

In this Eastern Cooperative Oncology Group (ECOG) phase II study, dibromodulcitol (DBD) and a combination of actinomycin D, hydroxyurea, and cyclophosphamide (AHC) were compared with methyl-CCNU, the current ECOG standard, in patients who had received no prior chemotherapy for disseminated malignant melanoma. The response rates were 6% (3/50) for AHC, 9% (3/34) for DBD, and 14% (7/49) for methyl-CCNU. Median survival times were 4, 5, and 6 months, respectively. Neither regimen appears to offer any advantage over methyl-CCNU as front-line therapy for patients with disseminated melanoma.

Adolescent↗