Myeloid growth factors clinical practice guidelines in oncology.
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
Jeffrey Crawford
Publications and source records attributed to Jeffrey Crawford.
Shifting guidelines for myeloid growth factors: applications in cancer chemotherapy.
Neutropenia is a frequent dose-limiting complication of chemotherapy. Although myeloid growth factors decrease the risk of febrile neutropenia and the resulting complications of hospitalizations, dose delays, and dose reductions, not all patients need or benefit from the prophylactic administration of myeloid growth factors. A recent risk model showed that the predictors of febrile neutropenia include anthracycline use, poor performance status, and low pretreatment blood counts. These predictors may be used in addition to the intensity of the chosen chemotherapy regimen to determine whether a patient warrants primary prophylaxis with myeloid growth factors. The 2005 guidelines of the National Comprehensive Cancer Network call for primary prophylactic use in all patients with a risk of febrile neutropenia above 20%. Other recent studies show that pegylated filgrastim is also effective at preventing febrile neutropenia in patients receiving intermediate- risk chemotherapy.
Antineoplastic Agents↗
Carboplatin/paclitaxel or carboplatin/vinorelbine followed by accelerated hyperfractionated conformal radiation therapy: report of a prospective phase I dose escalation trial from the Carolina Conformal Therapy Consortium.
PURPOSE: To prospectively determine the maximum-tolerated dose of accelerated hyperfractionated conformal radiotherapy (RT; 1.6 Gy bid) for unresectable locally advanced lung cancer (IIB to IIIA/B) following induction carboplatin/paclitaxel (C/T) or carboplatin/vinorelbine (C/N). METHODS: Induction chemotherapy, C/T or C/N, was followed by escalating doses of conformally-planned RT (73.6 to 86.4 Gy in 6.4-Gy increments). Concurrent boost methods delivered 1.6 and 1.25 Gy bid to the gross and clinical target volumes, respectively. RESULTS: Between November 1997 and February 2002, 44 patients were enrolled (median age, 59 years; 59% male; stage III, 98%; median tumor size, 4 cm). Thirty-nine patients completed induction chemotherapy: 19 had a partial response, seven progressed, 15 had no response, and three were not assessable. Chemotherapy-associated toxicities were similar in the two chemotherapy groups. The incidence of grade > or = 3 RT-induced toxicity was 1/13, 2/14, and 4/12 at 73.6, 80, and 86.4 Gy, respectively, thus defining the maximum tolerated dose at approximately 80 Gy. Toxicities were in both lung and esophagus and were similar in the two chemotherapy arms. With a median followup of 34 months in the survivors, the actuarial 2-year survival was 47%, the median survival was 18 months. Fifteen patients had tumor relapse: 5 local failures in the high-dose volume, 2 regional failures outside of the high-dose volume, and 8 distant metastases. CONCLUSION: High-dose conformal twice-daily radiation therapy to approximately 80 Gy appears tolerable in well-selected patients with unresectable lung cancer following either C/T or C/N. Dose-limiting toxicities are mainly pulmonary and esophageal.
Adult↗
Incidence and predictors of low chemotherapy dose-intensity in aggressive non-Hodgkin's lymphoma: a nationwide study.
PURPOSE: To assess the incidence of and risk factors for reduced relative dose-intensity (RDI) in patients treated with chemotherapy for aggressive non-Hodgkin's lymphoma (NHL). METHODS: A nationwide survey was conducted of 567 oncology practices with data extracted from the records of 4,522 patients with aggressive NHL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP); CHOP-rituximab (CHOP-R); or cyclophosphamide, mitoxantrone, vincristine, and prednisone (CNOP). The primary outcome was the average RDI for each regimen based on both planned and reference standards. Other assessments included the incidence of febrile neutropenia and patterns of colony-stimulating factor (CSF) use, as well as the average RDI in high-risk subgroups. RESULTS: Dose reductions > or = 15% occurred in 40% of patients and treatment delays > or = 7 days occurred in 24% of patients, resulting in 53% and 48% of patients receiving an RDI less than 85% of the minimum six-cycle and National Comprehensive Cancer Network guideline standards, respectively. Reduced RDI was more prevalent in older patients, with 60% of patients older than 60 years receiving RDI less than 85%. Multivariate analysis identified several independent predictors for reduced RDI, including age older than 60 years, advanced disease stage, poor performance status, and no prophylactic CSF use. Age was no longer a significant risk factor in patients who received prophylactic CSF. CONCLUSION: Patients with aggressive and potentially curable NHL treated with CHOP, CHOP-R, or CNOP frequently receive reduced RDI. Predictive models based on the risk factors identified for reduced RDI should enable the targeted use of appropriate supportive care, facilitating the delivery of full chemotherapy doses on schedule.
Aged↗
Preclinical and clinical evaluations of ABX-EGF, a fully human anti-epidermal growth factor receptor antibody.
The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, with an extracellular ligand-binding domain and intracellular tyrosine kinase domain. Ligand binding induces EGFR dimerization and autophosphorylation on several tyrosine residues in the intracellular domain, leading to mitogenic signal transduction. EGFR overexpression correlates with a poor prognosis and is often associated with malignant transformation in a variety of epithelial cancers. ABX-EGF is a high-affinity (dissociation constant K(D) = 5 x 10(-11) M) fully human IgG2 monoclonal antibody against human EGFR. ABX-EGF binds EGFR and blocks receptor binding of EGF and transforming growth factor-alpha, inhibiting EGFR tyrosine phosphorylation and tumor cell activation. ABX-EGF prevents tumor formation and eradicates large, established A431 tumors in xenograft models. Tumor growth inhibition occurs at relatively low doses, without concomitant chemotherapy or radiotherapy. When combined with chemotherapeutic agents, ABX-EGF has resulted in additive antitumor activity. A Phase I clinical trial has demonstrated activity in several tumor types, and the results from a Phase II trial for renal cell cancer also showed modest activity. Therapy was generally well tolerated without statistically significant adverse events. Monoclonal antibody blockade of EGFR represents a new and exciting direction in cancer therapy.
Animals↗
Chemotherapy-induced neutropenia: risks, consequences, and new directions for its management.
Cytotoxic chemotherapy suppresses the hematopoietic system, impairing host protective mechanisms and limiting the doses of chemotherapy that can be tolerated. Neutropenia, the most serious hematologic toxicity, is associated with the risk of life-threatening infections as well as chemotherapy dose reductions and delays that may compromise treatment outcomes. The authors reviewed the recent literature to provide an update on research in chemotherapy-induced neutropenia and its complications and impact, and they discuss the implications of this work for improving the management of patients with cancer who are treated with myelosuppressive chemotherapy. Despite its importance as the primary dose-limiting toxicity of chemotherapy, much concerning neutropenia and its consequences and impact remains unknown. Recent surveys indicate that neutropenia remains a prevalent problem associated with substantial morbidity, mortality, and costs. Much research has sought to identify risk factors that may predispose patients to neutropenic complications, including febrile neutropenia, in an effort to predict better which patients are at risk and to use preventive strategies, such as prophylactic colony-stimulating factors, more cost-effectively. Neutropenic complications associated with myelosuppressive chemotherapy are a significant cause of morbidity and mortality, possibly compromised treatment outcomes, and excess healthcare costs. Research in quantifying the risk of neutropenic complications may make it possible in the near future to target patients at greater risk with appropriate preventive strategies, thereby maximizing the benefits and minimizing the costs.
Aged↗
The importance of chemotherapy dose intensity in lung cancer.
The evidence for the importance of maintaining full dose on schedule chemotherapy for lung cancer varies considerably by histologic type. Several studies have evaluated chemotherapy dose and dose intensity in small cell lung cancer; fewer studies have evaluated the importance of chemotherapy in non-small cell lung cancer. The current guidelines of the National Comprehensive Cancer Network recommend adjuvant chemotherapy in most patients with resectable disease, and there is increasing evidence that chemotherapy benefits elderly patients as much as younger patients. Clinical trials in the setting of palliative treatment of advanced non-small cell lung cancer have focused on testing new regimens rather than evaluating the impact of maintaining the dose and schedule of standard chemotherapy regimens. However, in light of the potential curative role of chemotherapy in the adjuvant setting, the optimal doses and schedules of these regimens may have an important impact on outcomes. In addition, data suggest that responses in the neoadjuvant setting correlate with survival, and this may also be an appropriate setting in which to test the effect of the chemotherapy dose and schedule. Survival is the primary measure of treatment efficacy, but other end points, such as quality of life and disease stability, should also be considered in advanced disease. Because new regimens will shape the choice of treatment in the adjuvant and neoadjuvant settings, it is important to determine the significance of maintaining full dose on schedule with conventional chemotherapy regimens to ensure optimal outcomes in the treatment of lung cancer.
Antineoplastic Combined Chemotherapy Protocols↗
Incidence and predictors of low dose-intensity in adjuvant breast cancer chemotherapy: a nationwide study of community practices.
PURPOSE: This retrospective study was undertaken to assess practice patterns in adjuvant chemotherapy for early-stage breast cancer (ESBC) and to define the incidence and predictive factors of reduced relative dose-intensity (RDI). PATIENTS AND METHODS: A nationwide survey of 1,243 community oncology practices was conducted, with data extracted from records of 20,799 ESBC patients treated with adjuvant chemotherapy. Assessments included demographic and clinical characteristics, chemotherapy dose modifications, incidence of febrile neutropenia, and patterns of use of colony-stimulating factor (CSF). Dose-intensity was compared with published reference standard regimens. RESULTS: Dose reductions > or =15% occurred in 36.5% of patients, and there were treatment delays > or =7 days in 24.9% of patients, resulting in 55.5% of patients receiving RDI less than 85%. Nearly two thirds of patients received RDI less than 85% when adjusted for differences in regimen dose-intensity. Multivariate analysis identified several independent predictors for reduced RDI, including increased age; chemotherapy with cyclophosphamide, methotrexate, and fluorouracil, or cyclophosphamide, doxorubicin, and fluorouracil; a 28-day schedule; body-surface area greater than 2 m2; and no primary CSF prophylaxis. CSF was often initiated late in the chemotherapy cycle. CONCLUSION: Patients with ESBC are at substantial risk for reduced RDI when treated with adjuvant chemotherapy. Patients at greatest risk include older patients, overweight patients, and those receiving three-drug combinations or 28-day schedules. Predictive models based on such risk factors should enable the selective application of supportive measures in an effort to deliver full dose-intensity chemotherapy.
Adolescent↗
Risk of long-term complications after TFG-beta1-guided very-high-dose thoracic radiotherapy.
PURPOSE: To report the incidence of late complications in long-term survivors of very-high-dose thoracic radiotherapy (RT) treated on a prospective clinical trial. METHODS AND MATERIALS: Patients with locally advanced or medically inoperable non-small-cell lung cancer received three-dimensional conformal RT to the primary tumor and radiographically involved lymph nodes to a dose of 73.6 Gy at 1.6 Gy twice daily. If the plasma transforming growth factor-beta1 (TGF-beta1) level was normal after 73.6 Gy, additional twice-daily RT was delivered to successively higher total doses until the maximal tolerated dose was reached. Patients within a given dose level were followed for 6 months before escalation to the next dose level was permitted. Late complications were defined according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. RESULTS: Thirty-eight patients were enrolled between 1996 and 1999. Twenty-four patients were not eligible for radiation dose escalation beyond 73.6 Gy because of persistently abnormal TGF-beta1 levels. Fourteen patients received dose escalation (80 Gy in 8; 86.4 Gy in 6). Grade 3 or greater late complications occurred in 4 of 24, 1 of 8, and 2 of 6 patients treated to 73.6, 80, and 86.4 Gy, respectively. The corresponding patient numbers with late Grade 4-5 toxicity were 3 of 24, 0 of 6, and 0 of 8. Overall, 7 (18%) of the 38 patients developed Grade 3-5 late toxicity. Nonpulmonary complications predominated (4 of 7). Five (71%) of seven serious complications developed within 11 months after RT; however, the remaining two complications (29%) occurred very late (at 43 and 62 months). The 5-year actuarial risk of late Grade 3-5 complications was 33%. CONCLUSION: Long-term survivors of very-high-dose RT for non-small-cell lung cancer have a significant risk of severe treatment-related complications. At these high dose levels, the predominant toxicity may no longer be pulmonary. All Grade 4-5 complications occurred in patients whose dose was limited to 73.6 Gy because of a persistently elevated TGF-beta1. Thus, persistently elevated plasma TGF-beta1 levels toward the end of RT may identify patients at greatest risk of severe complications.
Adult↗
Routine use of approximately 60 Gy once-daily thoracic irradiation for patients with limited-stage small-cell lung cancer.
PURPOSE: To review the outcome of patients with limited-stage small-cell lung cancer receiving daily thoracic irradiation (RT) to approximately 60 Gy. METHODS AND MATERIALS: The records of patients treated with RT for limited-stage small-cell lung cancer between 1991 and 1999 at Duke University were retrospectively reviewed. Sixty-five patients were identified who had received continuous course once-daily 1.8-2 Gy fractions to approximately 60 Gy (range 58-66). All patients received chemotherapy (CHT); 32 received concurrent RT/CHT and 33 sequential CHT and then RT. Prophylactic cranial RT was administered to 17 patients. The time from diagnosis to local failure, tumor progression, and death was assessed using actuarial methods. The median follow-up for all patients was 16.7 months and for surviving patients was 29.6 months. The median age was 64 years (range 36-83), and the median Karnofsky performance status was 80 (range 50-100). RESULTS: The 3-year actuarial rate of local failure, progression-free survival, and overall survival was 40%, 25%, and 23%, respectively. One case of acute Grade 3 esophagitis developed. Ten late complications occurred: four pulmonary, two esophageal, two infectious, one leukemia, and one retinal toxicity with prophylactic cranial RT. Six were mild and resolved with treatment. CONCLUSION: CHT plus approximately 60 Gy of once-daily RT for limited-stage small-cell lung cancer was generally well tolerated. The survival rates were less than have been reported using 45 Gy in 1.5-Gy twice-daily fractions (2-year overall survival rate 47% compared with 30% in this study), but may be comparable because fewer than one-half our patients received concurrent CHT/RT and only 26% received prophylactic cranial RT. The relatively low rate of normal tissue morbidity in our patients supports the use of conventional once-daily fractionation to > or = 60 Gy. A randomized trial would be required to compare the outcomes after maximally tolerated dose twice-daily RT vs. maximally tolerated dose daily RT.
Adult↗
Once-per-cycle pegfilgrastim (Neulasta) for the management of chemotherapy-induced neutropenia.
Filgrastim (r-metHuG-CSF) was approved in the United States in 1991 for use in decreasing the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies treated with myelosuppressive chemotherapy. Colony-stimulating factors such as filgrastim are a significant advance in the supportive care of patients with cancer. However, because of its short half-life, filgrastim requires daily dosing by injection to maintain its effects on the bone marrow. Pegfilgrastim (Neulasta; Amgen, Thousand Oaks, CA) is a longer-acting, self-regulating form of filgrastim created by the covalent linkage of a 20-kd polyethylene glycol molecule to the N-terminal of the filgrastim molecule. The molecular characteristics of pegfilgrastim result in a longer terminal half-life, making once-per-chemotherapy-cycle administration possible. The results from two randomized double-blind phase III clinical trials in patients with breast cancer treated with myelosuppressive chemotherapy showed that a single dose of pegfilgrastim provides neutrophil support comparable with that provided by an average of 11 daily injections of filgrastim. Pegfilgrastim has also been shown to be comparable to filgrastim in reducing neutropenic complications in patients treated with chemotherapy for lymphoma. Data from three clinical trials have been presented: a randomized controlled trial in elderly patients treated with CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) for relapsed or refractory non-Hodgkin's lymphoma; a randomized controlled trial in patients treated with ESHAP (etoposide/methylprednisolone/cisplatin/cytarabine) for relapsed or refractory lymphoma; and a study in patients with newly diagnosed non-Hodgkin's lymphoma. The safety profile of pegfilgrastim is comparable to that of filgrastim in the clinical settings studied to date. The once-per-cycle administration of pegfilgrastim may improve patient quality of life because it is less disruptive to patients and caregivers, and increase adherence because no doses are missed, thus further advancing the management of chemotherapy-induced neutropenia and its consequences.
Antineoplastic Agents↗
Small-cell lung cancer: a review of clinical trials.
Small-cell lung cancer (SCLC) is expected to account for 25% of the approximate 170,000 cases of lung cancer diagnosed in the United States in 2002. Although sensitive and responsive to chemotherapy, SCLC has an increased propensity for early metastases, with relapses being common and long-term survival rates being poor. Clinical trials have played a vital role in expanding our knowledge base for this disease and have resulted in newer modalities, including chemotherapeutic agents, prophylactic cranial irradiation, and thoracic radiotherapy designed to improve overall outcomes. Clinical trials have also served to clarify the role of surgery in a disease that traditionally has been thought to be nonoperable. This review will focus on the results of clinical trials that have had an effect on the treatments of patients with limited and extensive-stage SCLC, with recommendations from the National Comprehensive Cancer Network being emphasized.
Antineoplastic Combined Chemotherapy Protocols↗
Risk of febrile neutropenia among patients with intermediate-grade non-Hodgkin's lymphoma receiving CHOP chemotherapy.
We sought to identify risk factors associated with the time to febrile neutropenia in patients with intermediate-grade, non-Hodgkin's lymphoma (NHL) who were receiving treatment with CHOP chemotherapy. Data were collected from 12 community and academic oncology practices participating in the Oncology Practice Pattern Study between 1991 and 1999. We reviewed the medical records of 577 intermediate-grade NHL patients who received initial CHOP chemotherapy and evaluated risk factors associated with time to first febrile neutropenic event. A febrile neutropenic event was defined as a body temperature of > 100.6 degrees F and an ANC nadir < 1000/mm3. A total of 160 patients experienced 224 febrile neutropenic events. The risk of febrile neutropenia was significantly associated with age > or = 65 years (p = 0.001), cardiovascular disease (p = 0.020), renal disease (p = 0.006), baseline hemoglobin < 12 g/dl (p = 0.018), > 80% planned average relative dose intensity (ARDI; p = 0.018), and no prophylactic colony-stimulating factor (CSF) use (p = 0.046). First febrile neutropenic events occurred by day 14 of cycle 1 in one-half of patients experiencing febrile neutropenia. In multivariate analysis, the risk of febrile neutropenia remained significantly associated with age > or = 65 years (HR = 1.65, 95% CI: 1.18-2.32), renal disease (HR = 1.91. 95% CI: 1.10-3.30), cardiovascular disease (HR = 1.54, 95% CI: 1.02-2.33), baseline hemoglobin < 12 g/dl (HR = 1.44, 95% CI: 1.04-2.00), > 80% planned CHOP ARDI (HR = 2.41, 95% CI: 1.30-4.47), and no CSF prophylaxis (HR = 2.13, 95% CI: 1.20-3.76). Such a model may permit the identification of patients at greatest risk of febrile neutropenia and, therefore, candidates for the selective prophylactic use of the hematopoietic growth factors.
Adult↗
Safety and efficacy of pegfilgrastim in patients receiving myelosuppressive chemotherapy.
The major dose-limiting toxicity associated with myelosuppressive chemotherapy is neutropenia, which can be ameliorated with proactive administration of granulocyte colony-stimulating factor (G-CSF). Pegfilgrastim is a long-acting G-CSF, recently approved by the Food and Drug Administration. The efficacy and safety of pegfilgrastim administered once/chemotherapy cycle have been evaluated in clinical trials involving patients treated with myelosuppressive chemotherapy for breast cancer, lung cancer, non-Hodgkin's lymphoma, and Hodgkin's disease. Two pivotal phase III trials in patients with breast cancer showed that pegfilgrastim is as effective as filgrastim regarding the primary efficacy end point, which was duration of grade 4 (severe) neutropenia in cycle 1 of myelosuppressive chemotherapy. Secondary end points were the frequency of fever with neutropenia (febrile neutropenia), duration of neutropenia in cycles 2-4, depth of the absolute neutrophil count (ANC) nadir, and time to ANC recovery in cycles 1-4. Once/cycle pegfilgrastim 100 microg/kg or 6 mg was as safe and effective as daily filgrastim 5 microg/kg in reducing the frequency and duration of severe neutropenia. A trend toward a greater reduction in the overall frequency of febrile neutropenia with pegfilgrastim was observed. The availability of pegfilgrastim simplifies the use of prophylactic G-CSF, with the potential to increase patient convenience and adherence in management of chemotherapy-induced neutropenia.
Antineoplastic Agents↗
Activation of tyrosine kinases in cancer.
Receptor and nonreceptor tyrosine kinases (TKs) have emerged as clinically useful drug target molecules for treating certain types of cancer. Epidermal growth factor receptor (EGFR)-TK is a transmembrane receptor TK that is overexpressed or aberrantly activated in the most common solid tumors, including non-small cell lung cancer and cancers of the breast, prostate, and colon. Activation of the EGFR-TK enzyme results in autophosphorylation, which drives signal transduction pathways leading to tumor growth and malignant progression. Randomized clinical trials of the EGFR-TK inhibitor gefitinib have demonstrated clinical benefits in patients with advanced non-small cell lung cancer whose disease had previously progressed on platinum- and docetaxel-based chemotherapy regimens. Bcr-Abl is a constitutively activated nonreceptor TK enzyme found in the cytoplasm of Philadelphia chromosome-positive leukemia cells. STI571 (imatinib mesylate) inhibits the Bcr-Abl TK, blocks the growth of these leukemia cells, and induces apoptosis. STI571 also inhibits other TKs, including the receptor TK c-kit, which is expressed in gastrointestinal stromal tumors. As TK inhibitors become available for clinical use, new challenges include predicting which patients are most likely to respond to these targeted TK inhibitors. Additional clinical trials are needed to develop the full potential of receptor and nonreceptor TK inhibitors for cancer treatment.
Apoptosis↗
Randomized phase II study of cisplatin with gemcitabine or paclitaxel or vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy for stage IIIB non-small-cell lung cancer: cancer and leukemia group B study 9431.
PURPOSE: To evaluate new drugs in combination with cisplatin in unresectable stage III non-small-cell lung cancer, Cancer and Leukemia Group B (CALGB) conducted a randomized phase II study of two cycles of induction chemotherapy followed by two additional cycles of the same drugs with concomitant radiotherapy. PATIENTS AND METHODS: Eligible patients received four cycles of cisplatin at 80 mg/m(2) on days 1, 22, 43, and 64 with arm 1: gemcitabine 1,250 mg/m(2) on days 1, 8, 22, and 29 and 600 mg/m(2) on days 43, 50, 64, and 71; arm 2: paclitaxel 225 mg/m(2) for 3 hours on days 1 and 22 and 135 mg/m(2) on days 43 and 64; and arm 3: vinorelbine 25 mg/m(2) on days 1, 8, 15, 22, and 29 and 15 mg/m(2) on days 43, 50, 64, and 71. Radiotherapy was initiated on day 43 at 2 Gy/d (total dose, 66 Gy). RESULTS: One hundred seventy-five eligible patients were analyzed. Toxicities during induction chemotherapy consisted primarily of grade 3 or 4 granulocytopenia. Grade 3 or 4 toxicities during concomitant chemoradiotherapy consisted of thrombocytopenia, granulo-cytopenia, and esophagitis. Response rates after completion of radiotherapy were 74%, 67%, and 73% for arms 1, 2, and 3, respectively. Median survival for all patients was 17 months. One-, 2-, and 3-year survival rates for the patients on the three arms were 68%/37%/28%, 62%/29%/19%, and 65%/40%/23%. CONCLUSION: Four cycles of gemcitabine, vinorelbine, or paclitaxel in combination with cisplatin can be administered at these doses and schedules. The observed survival rates exceed those of previous CALGB trials and may be attributable to the use of concomitant chemoradiotherapy. Induction chemotherapy added to concomitant chemoradiotherapy is being evaluated in a phase III randomized trial.
Adult↗
Survey of oncologists' perceptions of barriers to accrual of older patients with breast carcinoma to clinical trials.
BACKGROUND: Prior research has documented the under-representation in clinical trials of older patients with cancer. In part of a larger study to test the magnitude of these barriers to entering eligible older patients with carcinoma of the breast into clinical trials (Cancer and Leukemia Group B [CALGB] trial 9670), barriers to accruing eligible older patients to clinical trials were obtained from the physician's perspective. METHODS: One hundred fifty-six physicians (85% oncologists) who treated patients with breast carcinoma at 10 CALGB institutions completed a questionnaire concerning what they perceived as barriers to enrolling older patients with breast carcinoma on clinical trials and possible interventions that may improve accrual. RESULTS: Physicians' perceptions of the most important barriers to accrual of older patients were: 1) elderly patients have significant comorbid conditions that are not excluded by the protocol but that may affect how they would respond to treatment (16%); elderly patients have difficulty understanding what is required in a complicated treatment trial, resulting in poor compliance (16%); treatment toxicity (14%); and elderly patients often do not meet the eligibility criteria (15%). Oncologists most frequently suggested that the most effective interventions for improving the accrual of elderly patients to trials included making personnel available in the clinic to explain clinical trials to older patients and their families (25%) and providing physicians with educational materials concerning treatment toxicity in the elderly (18%). CONCLUSIONS: Physicians viewed barriers to accruing older patients with breast carcinoma to clinical trials as multidimensional, with the most important involving protocol requirements, treatment specific issues, and older patients' medical and cognitive characteristics. Thus, a variety of interventions would be needed to improve accrual of older patients to clinical trials, including increasing physicians' knowledge concerning treatment toxicity in the elderly, simplifying protocol requirements, and reducing treatment toxicity.
Adult↗
Relationship between changes in hemoglobin level and quality of life during chemotherapy in anemic cancer patients receiving epoetin alfa therapy.
BACKGROUND: Hemoglobin increases have been associated with quality of life (QOL) improvements in anemic cancer patients treated with epoetin alfa, but intervention generally has been reserved for symptomatic anemia or hemoglobin < 10 g/dL. Relationships among hemoglobin, functional status, and patient reported QOL have not been well characterized. METHODS: Data from two open-label, community-based trials of epoetin alfa therapy that enrolled 4382 anemic cancer patients undergoing chemotherapy were used to evaluate the relationship between hemoglobin changes and QOL changes. The authors measured QOL using the Linear Analog Scale Assessment (LASA) and the more detailed, disease-specific Functional Assessment of Cancer Therapy-Anemia (FACT-An) instrument. Analyses were performed to determine the incremental change in QOL associated with hemoglobin increases (1 g/dL increments). RESULTS: Cross-sectional analyses showed a nonlinear relationship and significant positive correlation between high hemoglobin levels and high LASA and FACT-An scores (r = 0.25 and 0.29, respectively, P < 0.01). Patients with hemoglobin increases of > or = 2 g/dL reported statistically significant improvements in five FACT-An items selected a priori specifically to reflect functional capacity. An incremental analysis used regression methods to identify the longitudinal relationship between incremental changes in hemoglobin and QOL scores. This relationship was found to be nonlinear, with the maximum QOL gain occurring at a hemoglobin level of 12 g/dL (range, 11-13 g/dL). Patients with low baseline QOL scores and longer time periods between baseline and final QOL assessments experienced significantly (P < 0.05) greater increases in overall QOL. Progressive disease at baseline, change in disease status from baseline to end of study, and increase in self-reported pain or nausea all had significant (P < 0.05) negative effects on QOL scores. CONCLUSIONS: A direct relationship exists between hemoglobin increases during epoetin alfa therapy and corresponding QOL improvements in cancer patients receiving chemotherapy across the clinically relevant hemoglobin range of 8-14 g/dL. These data suggest that the maximal incremental gain in QOL occurs when hemoglobin is in the range of 11-13 g/dL.
Anemia↗