Complication Of Chemotherapy In Patients Research Articles

Loss of microbiota-derived protective metabolites after neutropenic fever

Neutropenic fever (NF) is a common complication of chemotherapy in patients with cancer which often prolongs hospitalization and worsens the quality of life. Although an empiric antimicrobial approach is used to prevent and treat NF, a clear etiology cannot be found in most cases. Emerging data suggest an altered microbiota-host crosstalk leading to NF. We profiled the serum metabolome and gut microbiome in longitudinal samples before and after NF in patients with acute myeloid leukemia, a prototype setting with a high incidence of NF. We identified a circulating metabolomic shift after NF, with a minimal signature containing 18 metabolites, 13 of which were associated with the gut microbiota. Among these metabolites were markers of intestinal epithelial health and bacterial metabolites of dietary tryptophan with known anti-inflammatory and gut-protective effects. The level of these metabolites decreased after NF, in parallel with biologically consistent changes in the abundance of mucolytic and butyrogenic bacteria with known effects on the intestinal epithelium. Together, our findings indicate a metabolomic shift with NF which is primarily characterized by a loss of microbiota-derived protective metabolites rather than an increase in detrimental metabolites. This analysis suggests that the current antimicrobial approach to NF may need a revision to protect the commensal microbiota.

Survival analysis of elderly patients over 65 years old with stage II/III gastric cancer treated with adjuvant chemotherapy after laparoscopic D2 gastrectomy: a retrospective cohort study

BackgroundThe benefits of adjuvant chemotherapy for elderly patients with gastric cancer (GC) remain unknown because elderly patients are underrepresented in most clinical trials. This study aimed to evaluate the effectiveness and complications of adjuvant chemotherapy in patients > 65 years of age after laparoscopic D2 gastrectomy.MethodsThis was a single-center retrospective cohort study of elderly patients (> 65 years) with stage II/III GC who underwent curative laparoscopic D2 gastrectomy with R0 resection between 2004 and 2018. The adjuvant chemotherapy regimens included monotherapy (oral capecitabine) and doublet chemotherapy (oral capecitabine plus intravenous oxaliplatin [XELOX] or intravenous oxaliplatin, leucovorin, and 5-fluorouracil [FOLFOX]). The data were retrieved from a prospectively registered database maintained at the Department of General Surgery in Nanfang Hospital, China. The patients were divided as surgery alone and surgery plus adjuvant chemotherapy (chemo group). The overall survival (OS), disease-free survival (DFS), chemotherapy duration, and toxicity were examined.ResultsThere were 270 patients included: 169 and 101 in the surgery and chemo groups, respectively. There were 10 (10/101) and six (6/101) patients with grade 3+ non-hematological and hematological adverse events. The 1−/3−/5-year OS rates of the surgery group were 72.9%/51.8%/48.3%, compared with 90.1%/66.4%/48.6% for the chemo group (log-rank test: P = 0.018). For stage III patients, the 1−/3−/5-year OS rates of the surgery group were 83.7%/40.7%/28.7%, compared with 89.9%/61.2%/43.6% for the chemo group (log-rank test: P = 0.015). Adjuvant chemotherapy was significantly associated with higher OS (HR = 0.568, 95%CI: 0.357–0.903, P = 0.017) and DFS (HR = 0.511, 95%CI: 0.322–0.811, P = 0.004) in stage III patients.ConclusionsThis study suggested that adjuvant chemotherapy significantly improves OS and DFS compared with surgery alone in elderly patients with stage III GC after D2 laparoscopic gastrectomy, with a tolerable adverse event profile.

Mortality Among Neutropenic Cancer Patients Within the United States: The Association With Hospital Volume.

Neutropenia is a serious complication of chemotherapy in patients with solid tumors. The influence of hospital volume on outcomes in patients with neutropenia has been little investigated. We hypothesized that large-volume hospitals would have reduced mortality rates for neutropenic patients compared with small-volume institutions. We used the Nationwide Inpatient Sample database of the Healthcare Cost and Utilization Project, for the years 2007-2011. All adult inpatient episodes with a diagnosis of both neutropenia and solid-tumor malignancy were included. Hospital volume was defined as the number of neutropenic cancer episodes per institution per year. Mortality was defined as death during admission. A multilevel mixed-effects logistic regression model was applied. Twenty thousand three hundred and ten hospitalizations were included in the study, from 1,869 different institutions. Median age was 62 years. The overall inpatient mortality was 2.3%, and was dependent on age (age 50-59 years-1.6% and age 80-89 years-5.3%). The median number of neutropenic inpatient episodes in each institution per year was 14 (range, 1-168). Mortality was 3.3%, 2.7%, 2.2%, 2.2%, and 1.2% for each quintile of hospital volume (from lowest to highest volume, P < .001). Likewise, the proportion discharged home was 85.7%, 90.3%, 91.5%, 92.7%, and 95.4% (P < .001). The association between hospital volume and mortality remained significant after adjustment for patient-level and hospital-level variables. Patients with neutropenia hospitalized in large-volume institutions have a substantially lower mortality compared with those hospitalized at low-volume institutions. Further study is required to validate our findings or overcome potential biases, understand mechanism, and investigate how smaller institutions can improve outcomes.

Temperatures and blood counts in pediatric patients treated with chemotherapy for cancer, NCT01683370

Fever in neutropenia (FN) is the most frequent potentially lethal complication of chemotherapy in patients with cancer. The temperature limit defining fever (TLDF) for FN is based on scarce evidence. This prospective, single center observational study recruited non-selected pediatric patients diagnosed with cancer between ≥1 and ≤17 years in 2012 and 2013. Of 40 patients potentially eligible, 39 participated. Data of 8896 temperature measurements and 1873 complete blood counts (CBCs) were recorded over 289 months (24.1 years) of chemotherapy exposure time. During this time 43 FN episodes were diagnosed. In 32 episodes, FN diagnosis was based on reaching the local (i.e. Bern, Switzerland) standard TLDF of 39.0 °C; another 11 episodes had been captured by clinical judgement (i.e. temperature < 39.0 °C). These data can be used to simulate the effects of various TLDFs on the rate of FN diagnosis. We assume merging these data with other data sets is feasible.

Crocin treatment prevents doxorubicin-induced cardiotoxicity in rats

Doxorubicin (DOX)-induced cardiotoxicity is well-known as a serious complication of chemotherapy in patients with cancer. It is unknown whether crocin (CRO), main component of Crocus sativus L. (Saffron), could reduce the severity of DOX-induced cardiotoxicity. Therefore, this study was undertaken to assess the protective impact of CRO on DOX-induced cardiotoxicity in rats. The rats were divided into four groups: control, DOX (2mg/kg/48h, for 12days), and CRO groups that receiving DOX as in group 2 and CRO (20 and 40mg/kg/24h, for 20days) starting 4days prior to first DOX injection and throughout the study. Echocardiographic, electrocardiographic and hemodynamic studies, along with histopathological examination and MTT test were carried out. Our findings demonstrate that DOX resulted in cardiotoxicity manifested by decreased the left ventricular (LV) systolic and diastolic pressures, rate of rise/drop of LV pressure, ejection fraction, fractional shortening and contractility index, as compared to control group. In addition, histopathological analysis of heart confirmed adverse structural changes in myocardial cells following DOX administration. The results also showed that CRO treatment significantly improved DOX-induced heart damage, structural changes in the myocardium and ventricular function. In addition, CRO did not affect the in vitro antitumor activity of DOX. Taken together, our data confirm that CRO is protective against cardiovascular-related disorders produced by DOX, and clinical studies are needed to examine these findings in human.

Long-term arterial complications of chemotherapy in patients with cancer

The number of cancer survivors has gradually increased in recent decades. However, the cancer survivors are at risk for conditions related to their initial disease and its treatment, i.e. surgery, systemic treatment or radiotherapy. Cardiovascular complications, such as myocardial infarction, are common side effects of these therapies. Cardiovascular damage can occur during treatment or month to years after the initial treatment, as late effect of the cancer treatment. The pathophysiology of these effects is not yet fully understood, but an important part of the cardiovascular complications are thought to be the result of effects of anticancer agents on the structural and functional properties of the endothelium. Because these conditions can result in a high degree of morbidity and mortality, understanding how to improve the prevention, recognition, and treatment of vascular disease is an important medical priority in the care for cancer survivors. This review will focus on the long-term arterial complications of chemotherapy in cancer survivors. It will summarize the epidemiology and pathophysiology of these complications. Furthermore, important long-term clinical conditions related to these effects will be outlined, including cardiovascular risk management in terms of prevention, evaluation and therapy.

Intensive serial biomarker profiling for the prediction of neutropenic Fever in patients with hematologic malignancies undergoing chemotherapy: a pilot study.

Neutropenic fever (NF) is a life-threatening complication of myelosuppressive chemotherapy in patients with hematologic malignancies and triggers the administration of broad-spectrum antimicrobials. The ability to accurately predict NF would permit initiation of antimicrobials earlier in the course of infection with the goal of decreasing morbid complications and progression to septic shock and death. Changes in the blood level of inflammatory biomarkers may precede the occurrence of NF. To identify potential biomarkers for the prediction of NF, we performed serial measurements of nine biomarkers [C-reactive protein (CRP), protein C, interleukin (IL)-6, IL-8, IL-10, IL-1β, tumor necrosis factor-α, monocyte chemotactic protein-1, and intercellular adhesion molecule-1] using a multiplex ELISA array platform every 6-8 hours in patients undergoing myelosuppressive chemotherapy for hematologic malignancies. We found that the blood levels of IL-6 and CRP increased significantly 24 to 48 hours prior to the onset of fever. In addition, we showed that frequent biomarker monitoring is feasible using a bedside micro sample test device. The results of this pilot study suggest that serial monitoring of IL-6 and CRP levels using a bedside device may be useful in the prediction of NF. Prospective studies involving a larger cohort of patients to validate this observation are warranted. This trial is registered at ClinicalTrials.gov (NCT01144793).

Clinical and microbiological profile of febrile neutropenia in solid tumors and hematological malignancies at a tertiary cancer care center in South India.

Febrile neutropenia (FN) is a common but serious complication of chemotherapy in patients with solid tumors (ST) and hematological malignancies (HM). The epidemiology of FN keeps changing. The objective was to study the epidemiology of FN in adult patients with ST and HM at Kidwai Memorial Institute of Oncology, Bangalore - A tertiary cancer care center. Data of all episodes of FN that occurred during the period July 2011 to December 2011 were collected prospectively and analyzed. A total of 75 episodes of FN was observed during study period involving 55 patients. Febrile neutropenic episodes were more frequent in HM than in ST (57% vs. 43%). The rate of bloodstream infection was 14.7%. Gram-negative organisms were the predominant isolates (56.25%). Overall mortality rate was 13.3%. Presence of medical co-morbidity and positive culture predicted high mortality. Mortality rate did not differ significantly between HM and ST (14% vs. 12.5%; P = 1.0). Gram-positive bacteremia was associated with greater mortality than Gram-negative bacteremia (P = 0.02). Empiric antibiotic treatment for FN should be tailored to the locally prevalent pathogens and their susceptibility patterns.

Fatal tumor lysis syndrome in a patient with metastatic colon cancer after palliative chemotherapy

Summary Tumor lysis syndrome (TLS) is a rare but life-threatening complication of chemotherapy in patients with solid tumors such as colorectal cancer. Combination therapy comprising infusional irinotencan, 5-fluorouracil (5-FU), with folinic acid (FOLFIRI) and bevacizumab is considered the first choice for metastatic colorectal cancer. Reports of TLS after therapy with FOLFIRI and bevacizumab are rare. Here we report a case of TLS in a patient with metastatic colon cancer and peritoneal carcinomatosis, which developed 4 days after FOLFIRI and bevacizumab combination therapy. The patient died of acute renal failure 7 days after chemotherapy despite aggressive medical treatment. The large tumor burden, rapid proliferation of cancer cells, and azotemia prior to chemotherapy indicated a high risk of developing TLS in our patient. Although rare, steps to prevent TLS and to manage it aggressively if it occurs are required, especially for high-risk patients.

Omega-3 Poly-Unsaturated Fatty Acids for the Prevention of Severe Neutropenic Enterocolitis in Patients with Acute Myeloid Leukemia

Neutropenic enterocolitis is a potentially fatal complication of myeloablative chemotherapy in patients with acute myeloid leukemia. Omega-3 polyunsaturated fatty acids (PUFA) are precursors of potent anti-inflammatory prostaglandins. Our aim was to explore the safety and effectiveness of omega-3 PUFA added to parenteral nutrition in protecting leukemia patients from severe enterocolitis. Fourteen patients with acute myeloid leukemia who received omega-3 PUFA in a Phase II trial were compared with 66 consecutive control patients not getting this intervention. We performed crude and adjusted comparisons, using inverse probability of treatment weighting for adjusted analysis, and blind outcome assessment to minimize assessor bias. Primary outcome was severe enterocolitis (≥Grade 3). The crude odds ratio of Grade 3 colitis or higher was 1.36 (95% CI 0.37 to 4.96, P = 0.64), and the adjusted odds ratio was 0.79 (95% CI 0.35 to 1.78, P = 0.57). There was little evidence to suggest differences between groups in serious adverse events and overall mortality. Our results provide little evidence that addition of omega-3 PUFA is beneficial in this condition. Routine treatment with omega-3 PUFA is currently not warranted.

Treatment-related myelodysplasia in patients with primary brain tumors

Treatment-related myelodysplastic syndrome (t-MDS) and treatment-related acute myelogenous leukemia (t-AML) represent rare secondary events in patients with primary tumors of the nervous system and predominantly affect those treated with alkylating agents or topoisomerase II inhibitors. Temozolomide has become the standard chemotherapeutic agent for malignant gliomas. The emergence of this alkylating agent with little acute toxicity or cumulative myelosuppression has led to off-label protracted chemotherapy for many patients with malignant and even low-grade infiltrative gliomas, raising concern for increased risk of t-MDS/t-AML in the few long-term survivors. On the basis of an extensive literature search, we provide a discussion of epidemiology, pathogenesis, clinical presentation, diagnosis, and therapy of these disorders. t-MDS/t-AML remain rare complications of chemotherapy in patients with primary brain tumors, and the vast majority of patients die of their primary neoplasm. Prospective randomized studies with long-term follow-up are required to accurately assess the risk of t-MDS/t-AML; however, unless survival in the most common gliomas substantially increases, t-MDS/t-AML incidence will likely remain low in this patient population.

An Open-Label Multicenter Safety, Tolerability, and Efficacy Study of Recombinant Granulocyte Colony-Stimulating Factor in the Prevention of Neutropenic Complications in Breast Cancer Patients

The primary objective of this open-label, two chemotherapy arm, phase 4 study was to evaluate the safety and efficacy of newly developed recombinant granulocyte colony-stimulating factor (rG-CSF) used to prevent neutropenia-related complications in patients with metastatic breast cancer treated with docetaxel (75 mg/m(2)) and doxorubicin (50 mg/m(2)) or docetaxel (100 mg/m(2)) alone. A total of 50 patients who were treated with a maximum of 6 cycles of either docetaxel-doxorubicin (36 patients) or docetaxel alone (14 patients) every 21 days were recruited from 3 centers in Lithuania. All the patients received study medication rG-CSF at a dosage of 5 μg/kg per day (Sicor Biotech UAB, Teva Group) from day 2 of each cycle and continued for minimum 5 days or until absolute neutrophil count reached ≥1.5×10(9)/L. A total of 611 adverse events were reported. Most of them were related to myelotoxic chemotherapy. Two patients withdrew due to adverse events (neuropathy and bone pain). One patient died possibly because of pulmonary thromboembolism. The most frequently reported adverse events related to study drug in the docetaxel-doxorubicin and docetaxel groups were leukocytosis (22% and 21%, respectively), bone pain (19% and 21%, respectively), and headache (8% and 14%, respectively). The incidence of grade 4 neutropenia in both the groups was 47% and 29%, respectively, in all cycles and 42% and 21%, respectively, in cycle 1. The incidence of febrile neutropenia was 8% in cycle 1 and 14% across all cycles. The mean duration of febrile neutropenia was 2.1 days (SD, 1.9) in cycle 1 and 2.14 days (SD 2.0) across all cycles in both the treatment groups. This study provide data that the study drug rG-CSF has the expected safety and could be an efficacious medication to decrease the risk of febrile neutropenia and related complications of myelosuppressive chemotherapy in patients with metastatic breast cancer.

Risk of hospitalization for neutropenic complications of chemotherapy in patients with primary solid tumors receiving pegfilgrastim or filgrastim prophylaxis: A retrospective cohort study

Background: In a meta-analysis of data from randomized trials, the risk of febrile neutropenia during myelosuppressive chemotherapy was reported to be lower with pegfilgrastim prophylaxis than filgrastim prophylaxis. However, there is limited information on the comparative effectiveness of these agents in clinical practice. Objective: This study was undertaken to compare the risks of hospitalization for neutropenic complications of chemotherapy in US clinical practice in patients with primary solid tumors receiving pegfilgras-tim or filgrastim prophylaxis. Methods: This was a retrospective cohort study employing a US health insurance database. The source population included all patients who received chemotherapy for a primary solid tumor between January 2003 and December 2005 and who received filgrastim or pegfilgrastim during their first course of chemotherapy. All unique chemotherapy cycles were identified for each patient, and cycles in which pegfilgrastim or filgrastim was administered by cycle day 5 (considered to represent prophylaxis) were selected and pooled for analysis. The risks of hospitalization for neutro-penic complications (using both narrow and broad criteria) and for any reason were then compared between cycles in which filgrastim or pegfilgrastim prophylaxis was administered. Generalized estimating equations were used to control for potential confounding variables. Results: Filgrastim prophylaxis was used in 1193 unique chemotherapy cycles (mean [SD] number of days per cycle, 4.5 [3.3]); for pegfilgrastim prophylaxis, the number of unique chemotherapy cycles was 14,570. First-cycle use represented 16% of all cycles analyzed. The mean ages of patients receiving filgrastim and pegfilgrastim prophylaxis were 61 and 60 years, respectively. Breast cancer was the most common tumor type (52% and 51%), followed by non-Hodgkin's lymphoma (21% and 18%) and lung cancer (11% and 15%). Hospitalization for neutro-penic complications (narrow criterion) occurred during 2.1% of filgrastim cycles and 1.2% of pegfilgrastim cycles; hospitalization for neutropenic complications (broad criterion) occurred in a respective 4.8% and 3.1% of cycles; and hospitalization for all causes occurred in 8.7% and 6.3% of cycles (all, P < 0.01). The risks of hospitalization were consistently lower for chemotherapy cycles that involved pegfilgrastim prophylaxis compared with filgrastim prophylaxis (odds ratios = 0.64–0.73; P < 0.05). Conclusion: The risk of hospitalization for neutro-penic complications during cancer chemotherapy in clinical practice was approximately one third higher among patients who received filgrastim prophylaxis than among those who received pegfilgrastim prophylaxis.

Impact of diabetes mellitus on complications of chemotherapy and outcomes in older patients with breast cancer

553 Background: Diabetes mellitus (DM) is a recognized risk factor for several cancers and it can affect treatment toxicities and cancer outcomes. To date no studies have reported on specific complications of chemotherapy in patients with breast cancer (BC) and DM. Effect of DM on BC outcomes is unclear as studies have found conflicting results. We evaluated how diabetes affects patterns of care, complications of chemotherapy, and BC outcomes. Methods: Using a SEER-Medicare database we identified women age 66 years or older with Stage I-III breast cancer diagnosed between 1992 and 2002. We used ICD-9 and other codes to identify patients with DM, chemotherapy use, and toxicities of therapy. Multivariate Cox logistic regression analyses were performed to determine effect of DM on chemotherapy use, related toxicities, and outcomes. The risks of all-cause mortality and BC-specific mortality were estimated with Kaplan-Meier method. Results: Our cohort had 70,781 patients including 14,414 (20.4%) patients with DM. DM was associated with reduced odds of receiving anthracyclines (OR 0.78, CI 0.71–0.87) and taxanes (0.86, 0.75–0.99). 1,850 (15.6%) patients experienced any toxicity of chemotherapy. DM was associated with increased odds of experiencing hospitalization for toxicity of chemotherapy (1.38, 1.23–1.56), and with hospitalizations for infection/fever (1.43, 1.2–1.7), neutropenia (1.22, 1.03–1.45), and anemia (1.24, 1.05–1.47). DM negatively influenced all- cause mortality (HR 1.35, CI 1.31–1.39). There was a significant interaction between DM and chemotherapy use for BC-specific mortality. DM patients who did not receive chemotherapy had similar BC-specific mortality to non-DM patients (0.95, 0.88–1.03), but diabetics who did receive chemotherapy had worse BC-specific mortality than non-diabetics (1.20, 1.07–1.35). Conclusions: Patients with BC and DM despite receiving less toxic chemotherapy regimens are at increased risk of toxicities and hospitalization. This group of patients needs especially close attention in selection of chemotherapy and monitoring for toxicities. DM is associated with significantly higher risk of all-cause mortality and with worse BC-specific mortality among patients receiving adjuvant chemotherapy. No significant financial relationships to disclose.

Acute Tumor Lysis Syndrome Induced by Rituximab in Diffuse Large B-Cell Lymphoma

Acute tumor lysis syndrome (ATLS) is a well-known complication of chemotherapy in patients with rapidly proliferative hematopoietic malignancies such as lymphoma and leukemia. Rituximab anti-CD20 monoclonal antibody, an alternative to chemotherapy in the treatment of low-grade follicular lymphoma, also has been associated with ATLS. Rituximab-induced ATLS has been reported in 2 patients with chronic lymphocytic leukemia and in 2 patients with non-Hodgkin's lymphoma. I report another case of rituximab-induced ATLS in a patient with diffuse large B-cell lymphoma and review the cases in the literature.

Necrotizing Enterocolitis in Acute Lymphoblastic Leukemia Patients: Department Experience

Necrotizing enterocolitis is a severe complication of high-dose chemotherapy in patients with hematopoietic malignancies. Some patients with severe mucositis may develop necrosis of the intestine, leading to typhlitis and perforation of the intestinal tract. The patients have few obvious symptoms; thus, early diagnosis and prompt treatment of intestinal necrosis or bowel perforation seem critical for a good overall treatment outcome. We present 5 cases of intraabdominal complications in patients with acute lymphoblastic leukemia. All patients who underwent surgery survived the postoperative period. We also present a suggested algorithm for treatment of acute abdomen complications in leukemic patients.

The Prevention and Management of Cardiovascular Complications of Chemotherapy in Patients with Cancer

Cardiac toxicity of chemotherapeutic agents is a rapidly evolving area of increasing significance because of the increasing pool of long-term cancer survivors. The spectrum of cardiotoxicity with chemotherapeutic agents includes hypertension, QTc prolongation, acute cardiomyopathy, and bradyarrhythmias. The most common issue to arise has been cardiomyopathy with anthracyclines. Preventative strategies that have met with some success have included the use of less cardiotoxic analogs such as epirubicin and liposomal anthracycline preparations. The cardioprotectant agent dexrazoxane reduces cardiomyopathy but there are significant toxicity issues. Therefore, the main strategy for preventing cardiotoxicity remains careful monitoring with radionuclide angiography or echocardiography. The role of investigational markers of myocardial injury, such as troponin T or brain natriuretic peptide, remains of great interest. Management is according to conventional management of congestive heart failure. Trastuzumab is an antibody therapy directed against the human epidermal growth factor receptor-2 (HER2) receptor, which increases survival in patients with metastatic breast cancer and is under evaluation in the adjuvant setting. It also causes a decrease in left ventricular ejection fraction (LVEF) in a minority of patients. Incidence is increased if trastuzumab is given in conjunction with paclitaxel or anthracyclines. It differs from anthracycline cardiotoxicity in that it is not cumulative dose-dependent and often improves after withdrawal of treatment. Re-treatment with trastuzumab is often possible. Novel agents under development offer a different spectrum of toxicity to existing anticancer drugs and it appears likely that cardiovascular toxicity will be an important issue for many of these drugs, particularly those that target the tumor vasculature.

Prevention of chemotherapy-induced febrile neutropenia (FN) by antibiotics (AB) versus antibiotics plus granulocyte-colony stimulating factor (G-CSF) in small cell lung cancer (SCLC): A randomized phase III study

8002 Background: FN is a major complication of chemotherapy in patients (pts) with SCLC. G-CSF is used to prevent FN, but its primary use is only recommended in pts with a considerable (>40%) risk of FN (ASCO guidelines, JCO 2000). AB are also effective in preventing FN, even reduce infection-related mortality and are cost-effective (Tjan-Heijnen, Ann Oncol 2001). In this multicenter randomised phase III trial the role of combined primary prophylaxis with AB plus G-CSF in pts with SCLC at increased risk of FN was determined. Methods: Pts with SCLC-limited disease and performance status (PS) 2–3, or age over 60 years or judged not suitable for concurrent chemo/radiotherapy and pts with SCLC-extensive disease were considered at increased risk of FN. Pts were stratified for age (</≥ 60 years), PS (0–1/2), extend of disease (LD/ED) and line of therapy (1st/2nd) and randomised for primary prophylaxis with AB (ciprofloxacin 500mg + roxithromycin 150mg, bid, days 4–13) alone or in combination with G-CSF (filgrastim 5 μ g/kg/day days 4–13). Chemotherapy consisted of cyclophosphamide 1000mg/m2 day 1, doxorubicin 45mg/m2 day 1 and etoposide 100mg/m2 days 1,2,3, i.v., q 3 weeks, × 5. Primary endpoint: incidence of FN in first cycle, targeted accrual: N=156 pts (78/ arm). Results: See table;171 pts were eligible. Patient characteristics were well balanced. Conclusion: The addition of primary prophylactic G-CSF to prophylactic antibiotics significantly reduced the incidence of chemotherapy-related FN in SCLC patients at increased risk of FN, especially in the first cycle by 50%. Supported by a research grant of Dutch Healthcare Insurance Board. No significant financial relationships to disclose.

Prevention of chemotherapy-induced febrile neutropenia (FN) by antibiotics (AB) versus antibiotics plus granulocyte-colony stimulating factor (G-CSF) in small cell lung cancer (SCLC): A randomized phase III study

8002 Background: FN is a major complication of chemotherapy in patients (pts) with SCLC. G-CSF is used to prevent FN, but its primary use is only recommended in pts with a considerable (>40%) risk of FN (ASCO guidelines, JCO 2000). AB are also effective in preventing FN, even reduce infection-related mortality and are cost-effective (Tjan-Heijnen, Ann Oncol 2001). In this multicenter randomised phase III trial the role of combined primary prophylaxis with AB plus G-CSF in pts with SCLC at increased risk of FN was determined. Methods: Pts with SCLC-limited disease and performance status (PS) 2–3, or age over 60 years or judged not suitable for concurrent chemo/radiotherapy and pts with SCLC-extensive disease were considered at increased risk of FN. Pts were stratified for age (</≥ 60 years), PS (0–1/2), extend of disease (LD/ED) and line of therapy (1st/2nd) and randomised for primary prophylaxis with AB (ciprofloxacin 500mg + roxithromycin 150mg, bid, days 4–13) alone or in combination with G-CSF (filgrastim 5 μ g/kg/day days 4–13). Chemotherapy consisted of cyclophosphamide 1000mg/m2 day 1, doxorubicin 45mg/m2 day 1 and etoposide 100mg/m2 days 1,2,3, i.v., q 3 weeks, × 5. Primary endpoint: incidence of FN in first cycle, targeted accrual: N=156 pts (78/ arm). Results: See table;171 pts were eligible. Patient characteristics were well balanced. Conclusion: The addition of primary prophylactic G-CSF to prophylactic antibiotics significantly reduced the incidence of chemotherapy-related FN in SCLC patients at increased risk of FN, especially in the first cycle by 50%. Supported by a research grant of Dutch Healthcare Insurance Board. No significant financial relationships to disclose.

Neurotoxic complications of chemotherapy in patients with cancer: clinical signs and optimal management.

Neurotoxic side effects of chemotherapy occur frequently and are often a reason to limit the dose of chemotherapy. Since bone marrow toxicity, as the major limiting factor in most chemotherapeutic regimens, can be overcome with growth factors or bone marrow transplantation, the use of higher doses of chemotherapy is possible, which increases the risk of neurotoxicity. Chemotherapy may cause both peripheral neurotoxicity, consisting mainly of a peripheral neuropathy, and central neurotoxicity, ranging from minor cognitive deficits to encephalopathy with dementia or even coma. In this article we describe the neurological adverse effects of the most commonly used chemotherapeutic agents. The vinca-alkaloids, cisplatin and the taxanes are amongst the most important drugs inducing peripheral neurotoxicity. These drugs are widely used for various malignancies such as ovarian and breast cancer, and haematological cancers. Chemotherapy-induced neuropathy is clearly related to cumulative dose or dose-intensities. Patients who already have neuropathic symptoms due to diabetes mellitus, hereditary neuropathies or earlier treatment with neurotoxic chemotherapy are thought to be more vulnerable for the development of chemotherapy-induced peripheral neuropathy. Methotrexate, cytarabine (cytosine arabinoside) and ifosfamide are primarily known for their central neurotoxic side effects. Central neurotoxicity ranges from acute toxicity such as aseptic meningitis, to delayed toxicities comprising cognitive deficits, hemiparesis, aphasia and progressive dementia. Risk factors are high doses, frequent administration and radiotherapy preceding methotrexate chemotherapy, which appears to be more neurotoxic than methotrexate as single modality. Data on management and neuroprotective agents are discussed. Management mainly consists of cumulative dose-reduction or lower dose-intensities, especially in patients who are at higher risk to develop neurotoxic side effects. None of the neuroprotective agents described in this article can be recommended for standard use in daily practise at this moment, and further studies are needed to confirm some of the beneficial effects described.