Platelet transfusion for patients with cancer: clinical practice guidelines of the American Society of Clinical Oncology.

OBJECTIVE: To determine the most effective, evidence-based approach to the use of platelet transfusions in patients with cancer. OUTCOMES: Outcomes of interest included prevention of morbidity and mortality from hemorrhage, effects on survival, quality of life, toxicity reduction, and cost-effectiveness. EVIDENCE: A complete MedLine search was performed of the past 20 years of the medical literature. Keywords included platelet transfusion, alloimmunization, hemorrhage, threshold and thrombocytopenia. The search was broadened by articles from the bibliographies of selected articles. VALUES: Levels of evidence and guideline grades were rated by a standard process. More weight was given to studies that tested a hypothesis directly related to one of the primary outcomes in a randomized design. BENEFITS/HARMS/COST: The possible consequences of different approaches to the use of platelet transfusion were considered in evaluating a preference for one or another technique producing similar outcomes. Cost alone was not a determining factor. RECOMMENDATIONS: Appendix A summarizes the recommendations concerning the choice of particular platelet preparations, the use of prophylactic platelet transfusions, indications for transfusion in selected clinical situations, and the diagnosis, prevention, and management of refractoriness to platelet transfusion. VALIDATION: Five outside reviewers, the ASCO Health Services Research Committee, and the ASCO Board reviewed this document. SPONSOR: American Society of Clinical Oncology

A phase I trial of gemcitabine and infusional 5-fluorouracil (5-FU) in patients with refractory solid tumors: Louisiana Oncology Associates protocol no. 1 (LOA-1).

The major purposes of this study were to determine the maximally tolerated dose (MTD), dose-limiting toxicity (DLT), toxicity profile, and antitumor activity of gemcitabine (GEM) (Gemzar) and 5-fluorouracil (5-FU) combination therapy when administered to patients with advanced solid tumors. GEM was administered intravenously over 30 minutes on days 1, 8, and 15, and 5-FU was administered as a continuous intravenous infusion from day 1 through day 15 of each 28-day treatment course. Seventeen patients (13 men and 4 women, median age 57, all previously treated with chemotherapy) were treated with 68 courses at 3 dose levels: 800/200, 1,000/200, and 1,000/300 [GEM (mg/m2/week)/ 5-FU (mg/m2/day)]. Two further patients were not fully evaluable for toxicity; one died from a probable pulmonary embolism, and one refused further treatment after developing grade II mucositis and dermatitis after her day 1 to 7 treatment. At the third dose level, 2 of 4 patients developed grade III mucositis; one also developed grade IV neutropenia with fever and grade III thrombocytopenia. Patient accrual then resumed at the second dose level. At this level, 10 patients were treated, with two developing grade III mucositis. One of these patients also developed grade IV dermatitis. No other patient developed grade III or IV side effects. Prophylactic dexamethasone was initiated after 4 of the first 7 patients (including 1 of the not fully evaluable patients) developed dermatitis-grade IV in 1 patient and grade II in the remaining 3 patients. After the steroids were initiated, 4 of the last 11 patients treated developed dermatitis, but grade 1 in all cases. One patient with metastatic gastric cancer achieved a near-complete response of his gastric mass and adrenal metastasis. Minor responses were achieved in a patient with colon carcinoma and a patient with an ethmoid sinus adenoid cystic carcinoma. The MTD and recommended dose for phase II clinical trials of GEM and 5-FU on the above schedule is 1,000 mg/m2 and 200 mg/m2 respectively, with mucositis as the DLT.

Louisiana Tumor Registry: new developments and activities.

New developments in the Louisiana Tumor Registry (LTR) over the past 3 years have enhanced the operation of the LTR and broadened its functions. Recent funding for numerous special studies and research collaborations have expanded the registry activities from data collection and special etiologic studies to more completely address the mandates of registry law, which require the LTR to participate in studies of cancer causes, treatment, and survival in order to reduce cancer morbidity and mortality in Louisiana.

Louisiana Tumor registry: new developments and services provided.

Recent major developments in the Louisiana Tumor Registry (LTR) have enhanced the operation of LTR and broadened its available services. As a population-based cancer registry, the LTR assesses the magnitude of cancer burden in the state, identifies high-risk groups and areas, monitors time trends, evaluated cancer control programs, and provides resources to the health professionals in the state to address the considerable cancer problem in Louisiana. The registry is also available to provide research collaboration as well as to participate in cancer control and prevention programs.

Cancer of the esophagus in Acadiana.

Cancer of the esophagus is a frequently fatal cancer whose incidence appears to be increasing. In Acadiana, esophageal cancer occurs predominantly in males, with a higher incidence in black males. Results of surgical treatment, with or without other therapy, are dismal. Combined treatment with chemotherapy and radiotherapy improved survival when compared to surgery. Survival benefits with chemotherapy and radiotherapy are, unfortunately, modest at present.

Cancer in south Louisiana. Part 1: Tobacco-related cancers.

Tobacco-related cancers comprise about one third of the newly-diagnosed cancer in South Louisiana. These cancers are three times more common in men than in women. For cancers originating from anatomic sites where there is a direct contact with tobacco, ie, lung, larynx, oral cavity and pharynx, and esophagus, incidence rates for blacks are either higher than or similar to the rates for whites. For cancers of the bladder and the kidney, sites which have no direct contact with tobacco products, incidence rates are higher in whites than blacks. In general, white men in South Louisiana tend to have risks significantly higher than national for tobacco-related cancers, in particular, cancers of the lung (31% higher) and the larynx (42% higher). A similar pattern is observed for white females but is less pronounced. Black men in South Louisiana, on the other hand, have significantly lower rates than the SEER averages for cancers of the esophagus, oral cavity, and pharynx. Risks for other tobacco-related cancers are very comparable. There are very small differences in rates for black women between South Louisiana and SEER areas. Tobacco-related cancers are most preventable. Any effective cancer program in Louisiana must emphasize prevention and cessation of tobacco use.

Cancer in south Louisiana. Part II: Gastrointestinal tract cancers.

Incidence rates for the most common cancers of the gastrointestinal tract are presented for the 5 geographic regions in South Louisiana for the period 1983-1986. The risk of colorectal cancer, the most frequent GI cancer in males and females, is uniformly lower in these regions of South Louisiana than in other areas of the United States. Gastric cancer rates are significantly high in black males, as are pancreatic cancer rates in whites of both sexes compared to national rates.

Cancer in south Louisiana. Part III: Cancers of the breast and the reproductive system.

Cancers of the breast and reproductive system are less common in South Louisiana than other parts of the nation. The only exception is invasive cervical cancer. Incidence rates for breast cancer in South Louisiana women are 20% lower than the SEER combined rates, and rates for cancer of the uterine corpus and the ovary among white women are 43% and 32% lower respectively than the SEER averages. South Louisiana men also have risks 14% (whites) and 30% (blacks) less than the national of developing prostatic cancer. These significantly low rates are observed for all regions in South Louisiana. The reasons for the low rates are not clearly understood. Possible explanations include: less frequent use of cancer screening tests, high prevalence of hysterectomy, lower risk exposures, and host/genetic factors. The low incidence rates for these cancers are not accompanied by more favorable mortality outcomes, suggesting a poorer survival among Louisiana cancer patients partially due to late stage disease at the time of diagnosis and treatment. Programs to increase the accessibility of cancer screening tests and improve early detection are greatly needed.

Ground water and oil field waste sites: a study in Vermilion Parish.

Water samples were obtained from 128 private water wells surrounding eight oil field waste sites in Vermilion Parish. The specimens were analyzed for five heavy metals: barium, arsenic, chromium, lead, and cadmium. Half of the specimens were then analyzed for 16 volatile organic compounds. A blood sample was obtained from healthy adults drinking water from the wells tested for volatile organic compounds and this blood sample was also analyzed for volatile organic compounds. None of the water samples had levels of heavy metals or volatile organic compounds that exceeded the National Primary Drinking Water Standards. Barium levels in excess of 250 parts per billion suggested that styrene, toluene, and chloroform might be present. Blood levels of volatile organic compounds were significantly higher than could be accounted for by water consumption with levels in smokers significantly higher than in nonsmokers. These data suggest that as yet there is no contamination of ground water supplies around these sites. Volatile organic accumulation in humans probably occurs from a respiratory rather than from an oral route.

Central nervous system effects of lactate infusion in primates.

The concentration of total lactate in cisternal fluid increased threefold, from 12.3 +/- 2.1 to 37.6 +/- 8.9 mg/dl, during a 20-min intravenous infusion of 1 M racemic sodium lactate (10 mEq/kg) in 3 anesthetized, mechanically ventilated baboons. Rises in cisternal lactate lagged behind arterial lactate increases, but occurred during the time interval in which susceptible humans typically panic in response to lactate infusion. Subsequent to cisternal lactate increases, cisternal pH and HCO3- concentration progressively increased during a 105-min interval following lactate infusion. No consistent changes in cisternal pCO2 occurred during or subsequent to lactate infusion. These preliminary findings fail to support the hypothesis that lactate-induced panic is mediated by increasing central nervous system pCO2. Instead, these data demonstrate that lactate can rapidly increase in the central nervous system during lactate infusion, suggesting new lines of investigation for studying the mechanisms responsible for lactate-induced panic.

Isoproterenol-induced panic attacks.

Eighty-six panic disorder patients and 45 nonpsychiatric controls were infused with isoproterenol at a rate of 1 microgram/min for up to 20 min in a placebo-controlled, double-blind study. Sixty-six percent of panic disorder patients experienced panic attacks during isoproterenol infusions, compared to 16% during placebo infusions. Nine percent of control subjects panicked with isoproterenol, but none panicked with placebo. Patients were more sensitive than controls to the anxiogenic effects of isoproterenol, as measured by subject self-ratings on a panic description scale. The frequency of panic attacks induced in patients was related to the dosage of isoproterenol; 79% of the patients who received a mean of 18.5 ng/min/kg of isoproterenol panicked. The panic attacks experienced by patients during isoproterenol infusions were similar to those experienced during placebo infusions.

Sodium lactate infusions after treatment with tricyclic antidepressants: behavioral and physiological findings.

Fourteen patients with panic disorder were infused with sodium lactate both before and after treatment with tricyclic antidepressants. All patients had panic attacks before treatment, and only five after treatment. There was a significant decrease in measures of anxiety prior to and during infusions after treatment. The patients were able to tolerate more lactate during reinfusions. The comparison of reinfusion panickers and nonpanickers revealed that the reinfusion panickers had higher levels of anxiety, as measured by psychological symptoms on the Panic Description Scale, during both their pretreatment and posttreatment infusions. Tricyclic antidepressants appear to increase the threshold for lactate-induced panic attacks.

Preinfusion anxiety and laboratory-induced panic attacks in panic disorder patients.

Seventy panic disorder patients participated in a double-blind, placebo-controlled, randomized infusion study in which sodium lactate and isoproterenol were used to induce panic anxiety. Patients who panicked during lactate, isoproterenol, and placebo infusions generally had higher preinfusion anxiety scores. These findings held true irrespective of the order the infusions were given. Stepwise multiple regression analyses comparing panickers with nonpanickers as the criterion variable revealed that the items "afraid of going crazy," "feeling unsteady," and "feeling paralyzed" on the Panic Description Scale had the highest predicting values.

Evaluation of fludarabine phosphate in small cell carcinoma. A Southwest Oncology Group Study.

Fludarabine phosphate was given as a 5 day bolus infusion to eleven evaluable patients with recurrent small cell lung carcinoma. Patients had failed on one prior treatment regimen. There were no responses in the eleven evaluable patients. Severe neurologic toxicity occurred in one patient. Fludarabine phosphate as given in this protocol was not an effective agent in recurrent small cell lung carcinoma.

Follow-up study of control subjects with lactate- and isoproterenol-induced panic attacks.

Eleven of 45 normal control subjects experienced panic attacks during lactate and/or isoproterenol infusions. Ten of the 11 subjects were followed up for a mean period of 32.5 months. Two subjects reported the development of spontaneous panic attacks during the follow-up period; one related the development of these attacks to the infusion experience. Neither subject met DSM-III criteria for panic disorder either before or after the infusions. Twenty-six healthy control subjects who did not experience panic attacks during the infusion experience did not report any attacks during a follow-up period of 31.1 months.

Lactate- and isoproterenol-induced panic attacks in panic disorder patients and controls.

In a double-blind study using sodium lactate and isoproterenol infusions to provoke panic attacks, 73 of 86 panic disorder patients and 10 of 45 controls panicked with lactate, and 58 of 86 patients and 4 of 45 controls panicked with isoproterenol. We measured baseline and peak anxiety ratings in 10 controls with lactate-induced panic attacks, 31 controls who did not panic during lactate infusions, and 63 panic disorder patients who did panic during lactate infusions. The controls who panicked with lactate had robust increases in their anxiety ratings very similar to the increases experienced by patients who panicked with lactate.

Effects of laboratory-induced panic-anxiety on subsequent provocative infusions.

The effects of infusion-induced panic-anxiety on subsequent pre-infusion anxiety ratings and infusion-induced panic attacks were studied in 64 panic disorder patients, in a double-blind randomized study using sodium lactate, isoproterenol, and placebo infusions. While there was a decrease of preinfusion anxiety from one infusion to the next infusion both for panickers and nonpanickers, there was no evidence of either a significant decrease or an increase in the frequency of subsequent panic attacks. These results suggest that there is neither a desensitizing nor a sensitizing effect of pharmacologically induced panic attacks on subsequent infusions in a serial three-infusion design.

A laboratory procedure for the induction of flashbacks.

The authors administered infusions of lactate intravenously to seven patients with a DSM-III diagnosis of posttraumatic stress disorder, six of whom also met DSM-III criteria for panic disorder. The lactate infusions resulted in flashbacks in all seven patients and panic attacks in six patients. The authors conclude that with further development intravenous lactate infusion may be used to study flashbacks and other dissociative phenomena and to determine the relationship between flashbacks and panic anxiety.