Three palonosetron regimens to prevent CINV in myeloma patients receiving multiple-day high-dose melphalan and hematopoietic stem cell transplantation.

BACKGROUND: Explore safety and efficacy of three palonosetron-containing regimens for emesis prevention over 7 days in multiple myeloma (MM) patients receiving melphalan (100 mg/m(2)) and hematopoietic stem cell transplantation (HSCT). PATIENTS AND METHODS: Randomized, double-blind pilot study in MM patients (n=73) receiving 1, 2, or 3 days of 0.25 mg palonosetron (30-s i.v. bolus) 30 min before melphalan (days -2 and -1) and HSCT (day 0). Patients received dexamethasone (20 mg i.v., days -2 and -1) immediately before or after study drug/placebo. Daily diaries recorded emesis, rescue medication, nausea duration, and adverse events (AEs). RESULTS: Seven-day complete protection (no emesis) occurred in 41.7% [95% confidence interval (CI) 22.1% to 63.4%], 41.7% (95% CI 22.1% to 63.4%), and 44.0% (95% CI 24.2% to 65.1%) of patients receiving 1, 2, or 3 days of palonosetron, respectively (P=0.43). Complete response (emesis free without rescue medication) occurred in 8.3%, 20.8%, and 20.0% (P=0.14). Common AEs (≥10%) were mild-to-moderate diarrhea, constipation, headache, insomnia, and flatulence. No serious AEs occurred. CONCLUSIONS: Palonosetron with dexamethasone was safe and effective in preventing emesis in MM patients receiving melphalan and HSCT. This pilot study with a limited number of patients suggests that multiple doses of palonosetron could be more effective than a single dose in making patients emesis free without need for rescue medication. However, even multiple doses of palonosetron resulted in only 20% of patients being emesis free without rescue medication, suggesting that further improvement will require development of more effective combination antiemetic therapy.

Costs of blood transfusion: a process-flow analysis.

PURPOSE: To determine the cost of transfusing 2 units (U) of packed RBCs at a comprehensive cancer center. METHODS: We performed a process-flow analysis to identify all costs of transfusing 2 U of allogeneic packed RBCs on an outpatient basis to patients with either (1) solid tumor who did not undergo bone marrow transplantation (BMT), (2) solid tumor who underwent BMT, (3) hematologic malignancy who did not undergo BMT, (4) hematologic malignancy who underwent allogeneic BMT, or (5) hematologic malignancy who underwent autologous BMT. We conducted structured interviews to determine the personnel time used and physical resources necessary at all steps of the transfusion process. RESULTS: The mean cost of a 2-U transfusion of allogeneic packed RBCs was $548, $565, $569, $569, and $566 for patients with non-BMT solid tumor, BMT solid tumor, non-BMT hematologic malignancy, allogeneic BMT hematologic malignancy, and autologous BMT hematologic malignancy, respectively. Sensitivity analysis showed that total transfusion costs were sensitive to variations in the amount of clinician compensation and overhead costs, but were relatively insensitive to reasonable variations in the direct costs of blood tests and the blood itself, or the probability or extent of transfusion reaction. CONCLUSION: The costs of the transfusion of packed RBCs are greater than previously analyzed, particularly in the cancer care setting.

Incidence, cost, and outcomes of bleeding and chemotherapy dose modification among solid tumor patients with chemotherapy-induced thrombocytopenia.

PURPOSE: To describe the incidence and outcomes of bleeding and chemotherapy dose modifications associated with chemotherapy-induced thrombocytopenia (platelets < 50,000/microL). PATIENTS AND METHODS: Six hundred nine patients with solid tumors or lymphoma were followed-up during 1,262 chemotherapy cycles complicated by thrombocytopenia for development of bleeding, delay or dose reduction of the subsequent cycle, survival, and resource utilization. The association between survival and bleeding or dose modification was examined using the Cox proportional hazards model. Predisposing factors were identified by logistic regression. RESULTS: Bleeding occurred during 9% of cycles among patients with previous bleeding episodes (P <.0001), baseline platelets less than 75,000/microL (P <.0001), bone marrow metastases (P =.001), poor performance status (P =.03), and cisplatin, carboplatin, carmustine or lomustine administration (P =.0002). Major bleeding episodes resulted in shorter survival and higher resource utilization (P <.0001). Chemotherapy delays occurred during 6% of cycles among patients with more than five previous cycles (P =.003), radiotherapy (P =.03), and disseminated disease (P =.04). They experienced similar clinical outcomes but used significantly more resources. Dose reductions occurred during 15% of cycles but were not associated with poor clinical outcomes or excess resource utilization. Significantly shorter survival and higher resource utilization were observed among the 20% of patients who failed to achieve an adequate response to platelet transfusion. CONCLUSION: The incidence of bleeding is low among solid tumor patients overall but exceeds 20% in some subgroups. These subgroups are easily identifiable using routinely available clinical information. A clinical prediction rule is being developed. Poor response to platelet transfusion is a clinically and financially significant downstream effect of thrombocytopenia and warrants further investigation.

Time to clinical response: an outcome of antibiotic therapy of febrile neutropenia with implications for quality and cost of care.

PURPOSE: To determine whether antibiotic regimens with similar rates of response differ significantly in the speed of response and to estimate the impact of this difference on the cost of febrile neutropenia. METHODS: The time point of clinical response was defined by comparing the sensitivity, specificity, and predictive values of alternative objective and subjective definitions. Data from 488 episodes of febrile neutropenia, treated with either of two commonly used antibiotics (coded A or B) during six clinical trials, were pooled to compare the median time to clinical response, days of antibiotic therapy and hospitalization, and estimated costs. RESULTS: Response rates were similar; however, the median time to clinical response was significantly shorter with A-based regimens (5 days) compared with B-based regimens (7 days; P =.003). After 72 hours of therapy, 33% of patients who received A but only 18% of those who received B had responded (P =.01). These differences resulted in fewer days of antibiotic therapy and hospitalization with A-based regimens (7 and 9 days) compared with B-based regimens (9 and 12 days, respectively; P <.04) and in significantly lower estimated median costs ($8,491 v $11,133 per episode; P =.03). Early discharge at the time of clinical response should reduce the median cost from $10,752 to $8,162 (P <.001). CONCLUSION: Despite virtually identical rates of response, time to clinical response and estimated cost of care varied significantly among regimens. An early discharge strategy based on our definition of the time point of clinical response may further reduce the cost of treating non-low-risk patients with febrile neutropenia.

The Multinational Association for Supportive Care in Cancer risk index: A multinational scoring system for identifying low-risk febrile neutropenic cancer patients.

PURPOSE: Febrile neutropenia remains a potentially life-threatening complication of anticancer chemotherapy, but some patients are at low risk for serious medical complications. The purpose of this study was to develop an internationally validated scoring system to identify these patients. MATERIALS AND METHODS: Febrile neutropenic cancer patients were observed in a prospective multinational study. Independent factors assessable at fever onset, predicting low risk of complications, on a randomly selected derivation set, were assigned integer weights to develop a risk-index score, which was subsequently tested on a validation set. RESULTS: On the derivation set (756 patients), predictive factors were a burden of illness indicating absence of symptoms or mild symptoms (weight, 5; odds ratio [OR], 8.21; 95% confidence interval [CI], 4.15 to 16.38) or moderate symptoms (weight, 3; OR, 3.70; 95% CI, 2.18 to 6.29); absence of hypotension (weight, 5; OR, 7.62; 95% CI, 2.91 to 19.89); absence of chronic obstructive pulmonary disease (weight, 4; OR, 5. 35; 95% CI, 1.86 to 15.46); presence of solid tumor or absence of previous fungal infection in patients with hematologic malignancies (weight, 4; OR, 5.07; 95% CI, 1.97 to 12.95); outpatient status (weight, 3; OR, 3.51; 95% CI, 2.02 to 6.04); absence of dehydration (weight, 3; OR, 3.81; 95% CI, 1.89 to 7.73); and age less than 60 years (weight, 2; OR, 2.45; 95% CI, 1.51 to 4.01). On the validation set, a Multinational Association for Supportive Care in Cancer risk-index score >/= 21 identified low-risk patients with a positive predictive value of 91%, specificity of 68%, and sensitivity of 71%. CONCLUSION: The risk index accurately identifies patients at low risk for complications and may be used to select patients for testing therapeutic strategies that may be more convenient or cost-effective.

Vascular access by physician assistants: evaluation of an implantable peripheral port system in cancer patients.

PURPOSE: To determine the ability of a physician assistant (PA) to insert, in an ambulatory setting, a peripheral subcutaneous implanted vascular-access device (VAD) and to evaluate the ability to transfer this training to a second PA. We also evaluated the performance and complications associated with this new device. PATIENTS AND METHODS: The Peripheral Access System (PAS) Port catheter system (Sims-Deltec Inc, St Paul, MN) was inserted in patients who required long-term (> 3 months) vascular access for infusion therapy. RESULTS: The first PA (PA-1) successfully inserted 57 of 62 devices (92%) after gaining experience with the technique in 10 patients (success rate, five of 10 [50%]; P = .003). The second PA (PA-2) was successful in eight of 10 initial attempts (80%) and 25 of 30 overall (83%). Complications were few and limited to phlebitis, thrombosis, and a low infection rate (0.2 per 1,000 catheter days). CONCLUSION: PAs can be taught to insert a peripheral subcutaneous implanted VAD. This technique is transferable from one PA to another, and the device studied is appropriate for outpatient VAD programs.

Ciprofloxacin-induced nephrotoxicity in patients with cancer.

Nephrotoxicity associated with ciprofloxacin is uncommon. Five patients with cancer who developed acute renal failure that followed treatment with ciprofloxacin are described and an additional 15 cases reported in the literature are reviewed. Other than elevation of serum creatinine levels, characteristic clinical manifestations and abnormal laboratory findings are not frequently present. Allergic interstitial nephritis is believed to be the underlying pathological-process. Definitive diagnosis requires performance of renal biopsy, although this is not always feasible. An improvement in renal function that followed the discontinuation of the offending antibiotic supports the presumptive diagnosis of ciprofloxacin-induced acute renal failure.

Early empiric antibiotic therapy for febrile neutropenia patients at low risk.

Although it is apparent that certain patients with febrile neutropenic episodes can benefit from outpatient antibiotic therapy, not all low-risk patients are treated in this fashion. There are barriers, real and perceived, to implementing this approach for patients, health care providers, and caregivers. Table 3 summarizes the advantages and disadvantages of ambulatory management of febrile neutropenic patients. For many patients and physicians, outpatient oral antibiotics may be preferred, whereas for others a more conservative approach might be needed in order to feel comfortable with treating this population on an outpatient basis. In this situation, patients can be treated in a stepwise fashion as shown in Table 4. These alternatives allow physicians and patients options to discuss when planning treatment strategies for febrile neutropenia.

Hyperbilirubinemia after single-stage radical cystectomy and ileal loop diversion.

One hundred ninety-two patients underwent single-stage radical cystectomy and ileal loop diversion over a three-year period. Postoperative hyperbilirubinemia occurred in 21 patients (10.9%) within the first ten days. Early hyperbilirubinemia occurred in 11 patients by postoperative day 5, accounting for 52 percent of the hyperbilirubinemic patients and 5.7 percent of the study population. Elevation persisted into the six to ten-day postoperative period for 9 at which time a total of 18 patients had bilirubin levels elevated above their presurgical values (P less than 0.001). This clinical observation appears to be benign and worthy of further investigation.

Colony stimulating factors in patients with fever and neutropenia.

Colony stimulating factors (CSFs), are essential for the regulation of the hematopoietic system and were developed by the pharmaceutical biotechnology industry in the early 1990s for the prevention of serious neutropenic complication after myelosuppressive chemotherapy. Both G-CSF and GM-CSF consistently lead to an increase in circulating white blood cells and a reduction in the incidence of fever and neutropenia after myelosuppressive chemotherapy in patients with solid tumors, hematologic malignancies, and those undergoing stem-cell transplantation. Their role in improving response rates to chemotherapy and overall survival is less clear.

Identifying risk factors for imminent death in cancer patients with acute dyspnea.

A substantial proportion of cancer patients presenting to an emergency center (EC) or clinic with acute dyspnea survives fewer than 2 weeks. If these patients could be identified at the time of admission, physicians and patients would have additional information on which to base decisions to continue therapy to extend life or to refocus treatment efforts on palliation and/or hospice care alone. The purpose of this study was to identify risk factors for imminent death (survival

Current management of disseminated intravascular coagulation.

Disseminated intravascular coagulation is a complex process seen in a wide variety of clinical disorders. The oncology patient may develop this syndrome either as a result of the neoplasm itself or of the treatment of the neoplasm. An understanding of the pathophysiology of disseminated intravascular coagulation is essential for diagnosis and treatment. Diagnosis is accomplished by correlating clinical and laboratory data. Treatment remains controversial, but reversal of the triggering mechanism is the single most important factor in successful treatment. Other interventions, including the use of heparin, antithrombin III, and hirudin, are being studied. Much remains to be understood about disseminated intravascular coagulation, and controlled clinical trials are needed to define optimal treatment.

Incorporating new modalities into practice guidelines: platelet growth factors.

The outcomes of thrombocytopenia are clinically serious (hemorrhage), costly to prevent and treat (platelet transfusions and hospitalization), and may result in delay of the subsequent cycle of chemotherapy. Oprelvekin, the first commercially available platelet growth factor, has been shown to be safe and effective in reducing the need for platelet transfusions. In placebo-controlled trials of patients with solid tumors receiving dose-intensive chemotherapy, 68% of oprelvekin recipients escaped transfusion altogether, compared with only 41% of those who received a placebo. Side effects are generally mild, reversible, and related to fluid retention. Although clinical trials provide evidence about how many patients, on average, can be expected to benefit from agents such as oprelvekin, the trials provide little information about which patients in the general oncology population will benefit. Guidelines based on clinical trial data are limited by this approach. An alternative approach is to develop a clinical profile or model of patients at high risk of developing serious clinical outcomes and target platelet growth factors to these patients through the use of guidelines. Other important components of the guideline development process include a thorough evaluation of the costs of treatments and side effects as well as a careful evaluation of patient's preferences for alternative treatment strategies. Guidelines limiting growth factor use to only those patients who are most likely to benefit provide an opportunity to use expensive new agents in a cost-effective, evidence-based fashion.

Hypertensive crisis.

Hypertensive crisis is an acute emergency requiring aggressive management. Its incidence has decreased in recent years but still is prevalent in the medical community. From review of past and present treatment regimens, the following recommendations can be considered. (1) In the treatment of malignant hypertension with associated CHF, sodium nitroprusside is still an excellent agent. It has a rapid onset of action and blood pressure can be easily titrated. Nitroglycerin is also another agent that can be used in this situation. (2) In the treatment of malignant hypertension with associated aortic dissection, trimethophan camsylate is the preferred agent. An alternative choice is the combination of nitroprusside and labetalol. (3) In the treatment of malignant hypertension with associated myocardial ischemia, an excellent choice is nitroglycerin. Labetalol also should be considered in this situation. (4) In the treatment of hypertension during pregnancy, hydralazine is still a good choice. Labetalol has also been shown to be efficacious. (5) In the treatment of malignant hypertension with associated cerebral ischemia, the following drugs should be considered: nitroprusside, nitroglycerin, and labetalol. The most important attribute of these agents is that they are nonsedating and rapid in onset. (6) In the treatment of postoperative hypertension the choices best suited are labetalol, enalapril, nitroprusside, and nitroglycerin. These agents are rapid in onset and all can be administered intravenously.

Influence of data display formats on physician investigators' decisions to stop clinical trials: prospective trial with repeated measures.

OBJECTIVE: To examine the effect of the method of data display on physician investigators' decisions to stop hypothetical clinical trials for an unplanned statistical analysis. DESIGN: Prospective, mixed model design with variables between subjects and within subjects (repeated measures). SETTING: Comprehensive cancer centre. PARTICIPANTS: 34 physicians, stratified by academic rank, who were conducting clinical trials. INTERVENTIONS: PARTICIPANTS were shown tables, pie charts, bar graphs, and icon displays containing hypothetical data from a clinical trial and were asked to decide whether to continue the trial or stop for an unplanned statistical analysis. MAIN OUTCOME MEASURE: Percentage of accurate decisions with each type of display. RESULTS: Accuracy of decisions was affected by the type of data display and positive or negative framing of the data. More correct decisions were made with icon displays than with tables, pie charts, and bar graphs (82% v 68%, 56%, and 43%, respectively; P=0.03) and when data were negatively framed rather than positively framed in tables (93% v 47%; P=0.004). CONCLUSIONS: Clinical investigators' decisions can be affected by factors unrelated to the actual data. In the design of clinical trials information systems, careful consideration should be given to the method by which data are framed and displayed in order to reduce the impact of these extraneous factors.