头孢吡肟单药治疗肺癌患者中性粒细胞减少伴发热的临床观察

目的 观察头孢吡肟单药治疗中性粒细胞减少伴发热的肺癌患者的临床疗效和并发症.方法 选择98例中性粒细胞减少伴发热的肺癌患者为研究对象,随机分为实验组(50例)和对照组(48例).实验组患者采用头孢吡肟单药治疗,对照组采用亚胺培南单药治疗.对2组患者的相关实验指标(中性粒细胞数、白细胞数、血小板数、红细胞数、超敏C反应蛋白和体温)、临床疗效和并发症发生率进行比较.结果 治疗前后,2组间相关实验指标比较,差异均无统计学意义(P＞0.05).组内的比较结果显示,治疗后2组患者的中性粒细胞和血小板计数较治疗前均明显升高(P＜0.05),超敏C反应蛋白和体温较均明显降低(P＜0.05),而白细胞数和红细胞数较治疗前无明显变化(P＞0.05).治疗3天后,实验组和对照组的临床有效率分别为86.0％和87.5％,治疗7天后,2组患者的临床有效率均提高,但2组之间差异无统计学意义(P＞0.05).2组患者的并发症发生率分别为8.0％和14.1％,差异无统计学意义(x2=2.14,P=0.19).结论 头孢吡肟单药可以有效治疗中性粒细胞减少伴发热的肺癌患者,其临床效果与亚胺培南相当.     

Empiric Treatment of Localized Infections in the Febrile Neutropenic Patient with Monotherapy

Empiric therapy is necessary for febrile, neutropenic patients in order to minimise morbidity and mortality. Certain agents are now available for monotherapy which offcrcomparable success to combinations of either an aminoglycoside with a β-lactam or two β-lactams. However, no regimen offers complete treatment under all circumstances in all patients. It is also apparent that febrile, neutropenic patients comprise a more heterogeneous group than just those with bacteraemia, clinically apparent infection and unexplained fever. Localized infections occur in just under a third of cases at the onset of fever and a similar number will develop during the course of fever. Mortality is higher in infections that are accompanied by bacteraemia and also those that develop subsequently, especially when related to the lung. The aetiological agent also differs with each type of infection as does the duration of fever and symptoms. Consequently modifications are required more often. The length of treatment may also differ. Therefore, during the first 3-4 days of empiric therapy, every effort should be made to identify incipient localized infections in addition to detecting bacteraemia. Changes in therapy can then be based on objective grounds rather than continued fever offering more patients individual treatment than is possible when relying only on the temperature chart.     

Imipenem in the Treatment of Febrile Neutropenic Children

Introduction: Infection of neutropenic children treated with malignancies is even now the major cause ofearly morbidity and mortality. Febrile neutropenic attacks without complications are successfully treated withwide-spectrum anti-pseudomonal cephalosporins or carbapenems. Objective: To determine the efficacy andsafety of imipenem in the treatment of febrile neutropenia in children with cancer. Materials and Methods:Twenty four patients who had a febrile neutropenic (FN) episodes followed by initiation of empirical imipenemtherapy were included in the study. Results: Of the patients, 10 (41.7%) had solid tumors, while 14 (58.3%) werediagnosed to have acute leukemia. Among all, 5 (20.8 %) and 15 (62.5 %) of the infections were identifiedmicrobiologically and clinically, respectively. Fever of unknown origin was observed in 4 (16.7 %) patients. Themean duration of neutropenia was 6.3 ± 1.4 (4-8) days in patients with solid tumors, and 9.3 ± 7.4 (3-25) days inthe group with leukemia. Average time of stay in hospital was 9.0 ± 4.1 (4-20) days for patients with solid tumors,and 14.4 ± 10.6 (4-33) days for patients with leukemia. FN duration was observed to be significantly longer inpatients with an ANC of less than 200/mm3, and in children who were not in remission for the underlyingmalignant disease. In addition, average time of stay in hospital was observed to be significantly longer in patientswho were not in remission for the underlying malign disease. All of the patients were discharged. The successrate of empirical therapy started with imipenem was found be 95.8 %. Conclusion: Imipenem is effective andsafe in the treatment of FN in pediatric cancer patients.     

Meropenem Monotherapy as an Empirical Treatment of Febrile Neutropenia in Childhood Cancer Patients

Introduction: Chemotherapy related neutropenia developing in oncologic patients is a significant conditionand major cause of morbidity and mortality. Febrile neutropenic attacks without complications can be successfullytreated with wide-spectrum anti-pseudomonal cephalosporins or carbapenems. Objective: We investigated theefficacy and safety of meropenem in the treatment of febrile neutropenia (FN) in children with cancer. Materialsand Methods: Twenty four patients who had a febrile neutropenic episodes followed by initiation of empiricalmeropenem therapy were included in the study. Results: Of all the patients, 13 (54.2%) had solid tumors, while11 (45.8%) were diagnosed to have acute leukemia. Among all, 7 (29.2%) and 15 (62.5%) infections were identifiedmicrobiologically and clinically, respectively. Fever of unknown origin was observed in 2 (8.3%) patients. Themean duration of neutropenia was 7.2 ± 3.1 (4-14) days in patients with solid tumors, and 9.3 ± 4.7 (2-17) days inthe group with leukemia. This difference was not statistically significant (log rank, p=0.063). Average time ofstay in hospital was 10.1 ± 6.4 (4-21) days for patients with solid tumors, and 15.9 ± 11.7 (5-37) days for patientswith leukemia (log rank, p=0.041). FN duration was observed to be significantly longer in patients with anabsolute neutrophil count (ANC) of less than 100/mm3 and even those with an ANC of less than 200/mm3, and inchildren who were not in remission for the underlying malign disease (p<0.05). While 22 (91.7%) of the patientswere discharged from the hospital, 2 (8.3%) died. The success rate of empirical therapy started with meropenemwas 87.5%. Conclusion: Meropenem is effective and safe for treatment of FN in pediatric cancer patients.     

The Efficacy of Mezlocillin-Amikacin Combination in Febrile Neutropenic Children with Oncologic Disease

Summary

The efficacy of mexlocillin-amikacin combination as empirical therapy for febrile neutropenic patients was studied in 30 children (21 males, 9 females) with various oncologic diseases aged 1-15 years (mean age 7.3±4.4) in the Istanbul Medical School, Oncologic Disease Research and Treatment Center, and Department of Pediatric Hematology-Oncology between January 1 and May 31, 1988.

The response rate was 76.6%. Profound persistent granulocytopenia (fewer than 100 ml) was present in 70% of the patients. In 63.3% of patients, the infections were microbiologically documented (60%) gram( + ) and 40% gram( - ).

The combination was well tolerated with hepatic and/or renal disturbances in 8 cases (26.6%). We conclude that mezlocillin-amikacin is an effective empirical combination in the initial treatment of infections in febrile neutropenic children with various oncologic diseases.     

Randomized Study of Cefepime versus Ceftazidime plus Amikacin in Patients with Solid Tumors Treated with High Dose Chemotherapy (HDC) and Peripheral Blood Stem Cell Support (PBSCS) with Febrile Neutropenia

Objective This randomized clinical trial evaluated the efficacy and safety of monotherapy with cefepime for patients with solid tumors treated with high dose chemotherapy (HDC) and peripheral blood stem cell support (PBSCS) with febrile neutropenia. Subjects Patients with solid tumors treated with HDC and PBSCS, that developed fever and neutropenia (absolute neutrophil count<500 cells/μL) were eligible, and randomly assigned to receive ceftazidime plus amikacin or cefepime. Results Fifty-one episodes were randomized, and all were evaluable (27 received ceftazidime plus amikacin arm, and 24 cefepime). Major efficacy endpoints did not show significant differences, with success rates of 44.4% and 54.2% (p=0.481) for the combination arm and the monotherapy arm, respectively. The proportion of patients that became afebrile in the first 24 hours was significantly higher in the cefepime group (41.7% vs 11.1%, respectively; p=0.012). However, due to its premature closure and small sample size, this study lacks the adequate power to definitely address this question. Conclusions Cefepime monotherapy appeared to have an equivalent efficacy and safety as empiric treatment in febrile neutropenia episodes in a high-risk population compared with ceftazidime and amikacin. Nevertheless, this study is not adequately powered to answer this question. Given the small number of patients randomized and the single-center nature of this study, these results must be cautiously interpreted. Presented in part at the meeting of the American Society of Clinical Oncology, Chicago, Illinois, May 2003 (abstr. 3387). A. Jimeno and A. Arcediano equally contributed to this work.     

A Randomized,Open-Labeled,Prospective Controlled Study to Assess the Efficacy of Frontline Empirical Intravenous Piperacillin/Tazobactam Monotherapy in Comparison with Ceftazidime Plus Amikacin for Febrile Neutropenia in Pediatric Oncology Patients

Background: Febrile neutropenia (FN) is the most common complication in pediatric oncology patients. Appropriate empirical antibiotics treatment is essential for treatment outcome. Methods: This study was a randomized prospective controlled study to demonstrate the efficacy of piperacillin/tazobactam (PIP/TZO) monotherapy compared with ceftazidime/amikacin in children with FN. Pediatric oncology patients at Chiang Mai University Hospital, diagnosed with FN, were randomized to receive either PIP/TZO 320 mg/kg/day divided every 8 hours or ceftazidime 100 mg/kg/day divided every 8 hours plus amikacin 15 mg/kg/day once daily. Treatment responses were compared between the two groups. Results: One-hundred and eighteen febrile neutropenic episodes in 70 patients (42 males and 28 females) were enrolled. The median age was 7 (3-10) years. The early response and complete response to initial treatment were achieved in 48/59 (81.4%) episodes and 41/59 (69.5%) episodes in PIP/TZO group compared with 40/59 (67.8%) episodes and 33/59 (55.9%) episodes in ceftazidime/amikacin group (p-value 0.091 and 0.128, respectively). Treatment modification in PIP/TZO group was required in 18/59 (30.5%) compared with 26/59 (44.1%) patients in ceftazidime/amikacin group (p-value 0.128). Similarly, the duration of fever, duration of neutropenia and duration of antibiotics treatment were not significantly different between two groups. No serious adverse events were observed. Conclusion: The treatment responses of PIP/TZO monotherapy and ceftazidime/amikacin therapy were not significantly different. Both therapies were effective for FN in pediatric oncology patients.     

Trimethoprim-Sulfamethoxazole plus Amikacin as First-Line Therapy and Imipenem/Cilastatin as Second Empirical Therapy in Febrile Neutropenic Patients with Hematological Disorders

One hundred and thirty-nine consecutive episodes of fever were evaluated in 55 patients with hematological disorders during persistent neutropenia. In 121 instances, patients were given trimethoprim-sulfamethoxazole + amikacin (TMP/SMZ + AMI) as an initial antibiotic regimen with clinical success in 51% (i.e. antibiotic treatment was not changed within the first 7 days).

Imipenem/cilastatin (I/C) therapy was instituted in: (a) 22 episodes with clinical failure and fever of unknown origin during TMP/SMZ + AMI therapy and (b) 18 episodes with a second fever episode during initially successful TMP/SMZ + AMI therapy. The response rate for all 40 I/C treated episodes was 80%. One neutropenic patient in the whole series died from infectious complications within four weeks from institution of therapy.

TMP/SMZ + AMI seems to be a safe and inexpensive «standard» antibiotic regimen in neutropenic patients. I/C appears to have good efficacy when used as secondary therapy after failure with TMP/SMZ + AMI.     

Cost-Effectiveness of Gemcitabine + Cisplatin vs. Gemcitabine Monotherapy in Advanced Biliary Tract Cancer

Objectives  

The ABC-02 trial demonstrated a statistically significant survival benefit associated with the addition of cisplatin to gemcitabine in the palliative treatment of advanced biliary tract cancer (BTC). Based on the ABC-02 findings, this analysis seeks to evaluate the cost-utility of adding cisplatin to standard gemcitabine therapy from a U.S. societal perspective.     

Efficacy and Safety of Once-Daily Amikacin in Combination with Ceftazidime in Critically Ill Adults with Severe Gram-Negative Infections

Abstract

Forty critically ill adult patients with severe Gram-negative infection were treated with once-daily amikacin combined with ceftazidime. The mean age was 56.6 ± 19 years and mean APACHE II score was 22.7 ± 6.6. Forty percent of patients required mechanical ventilation. The mean creatinine clearance at onset of therapy was 59.4 ± 28 ml/min. All bacterial isolates were sensitive to amikacin. Fixed doses of amikacin 15 mg/kg, 12 mg/kg, and 8 mg/kg body weight were given once daily to patients with estimated creatinine clearance of > 80 ml/min., 50-80 ml/min., and < 50 ml/min, respectively. Forty-two causative gram-negative bacteria were isolated from 40 patients. The most common bacteria were Pseudomonas aeruginosa (18), and Escherichia coli (10). Overall clinical success and bacteriological eradication occurred in 85% and 87.5% of patients; 78.9% and 79% of patients with hospital-acquired infections; 90.5% and 95.2% of patients with community-acquired infections; and 62.5% and 81.3% of patients requiring mechanical ventilation, respectively. Therapeutic failure was documented in 15% of patients. Death due to infection was scored in two patients. The remaining were all due to persistence of the initial causative bacteria in patients with hospital-acquired infections. Persistence was documented with Ps. aeruginosa (2), Serratia spp. (1), and Acinetobacter spp. (1). Overall mortality occurred in 22.5% patients. Death unrelated to infection occurred in 7 patients. There was no clinical evidence of ototoxicity in any of our patients, however, nephrotoxicity was documented in 5%. In conclusion, once-daily amikacin combined with ceftazidime is practical, efficacious and probably safe in critically ill infected patients.     

Key Pharmacokinetic Parameters of Isepamicin in Febrile Neutropenic Cancer Patients and in Women with Acute Pelvic Inflammatory Disease

Abstract

The pharmacokinetics (PK) of isepamicin were studied in 8 febrile neutropenic patients with hematologic malignancy and in 20 young women with acute pelvic inflammatory disease (PID). Isepamicin was given as a slow intravenous infusion over 30 min at a dose of 15 mg/kg once daily (OD). Serum levels of isepamicin were determined by fluorescence polarization immunoassay, and PK analyses were obtained based on a one-compartment open model after 24 hours (steady state) and after 7 days.

On day 1, the volume of distribution (V_d) of isepamicin, for both populations, appeared about 30% higher than classically reported in healthy individuals: 0.31 and 0.36 L/kg for neutropenic and PID patients respectively. However on day 7, V_d displayed significant reduction (0.28 and 0.27 L/kg, respectively for neutropenic and PID patients). A reduction of isepamicin clearance was also observed between day 1 and day 7 (137 vs 120 mL/min and 130 vs 101 mL/min for neutropenic and PID populations, respectively). Such changes are consistent with a significant increase in the C_max concentrations (45 vs 50 mg/L, and 38 vs 49 mg/L) and in the AUC (136 vs 158 and 137 vs 162 mg/L.h) observed after a week of treatment in neutropenic and PID patients, respectively.

In conclusion, taking into account the importance of reaching early active concentrations, we recommend the use of higher loading dose of isepamicin (>15 mg/kg) in neutropenic cancer patients and in women with PID, particularly in case of a combination with a possibly ineffective antibacterial agent, in case of infection with bacteria at upper limit of susceptibility, in the presence of high infectious inoculum or in the presence of sequestered sites of infection.     

Cost-effectiveness of cefepime + netilmicin or ceftazidime + amikacin or meropenem monotherapy in febrile neutropenic children with malignancy in Turkey.

Infection remains the major cause of morbidity and mortality in immunocompromised children with malignancy. In addition, the economic impact of antibiotic treatment should always be evaluated, especially in developing countries. In our center between January 1998 and January 1999, 73 children with hematological malignancies [acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML)]; 9 children with solid tumors (rhabdomyosarcoma, neuroblastoma) had 87 febrile neutropenic episodes (related to chemotherapy). These children were randomized prospectively into three treatment groups. The first group (n: 28) received cefepime plus netilmicin, while the second group (n: 29) was treated with ceftazidime plus amikacin and the third (n: 30) with meropenem as monotherapy. The aim of the study was to compare the success rates and cost of fourth generation cephalosporin plus aminoglycoside and monotherapy of meropenem with ceftazidime plus amikacin, which is the standard therapy for febrile neutropenia. Microbiologically documented infections were 29.9%, clinically documented infections were 9.2% and 60.9% of the febrile neutropenic episodes were considered to be FUO. Gram-positive microorganisms were the most commonly isolated agents from blood cultures [MRSA (Methicillin Resistant Staphylococcus aureus) in 6 patients and MSSA (Methicillin Sensitive Staphylococcus aureus) in 4 patients]. The success rates were 78.5%, 79.3% and 73.3 % for the 1st, 2nd and 3rd groups respectively. In 4 patients (4.5%) fever responded only to amphotericin-B therapy. There was no statistically significant difference between the three treatment regimens with respect to efficacy, safety and tolerance (chi2 test, p>0.05), but while the third and fourth generation cephalosporins + aminoglycosides were comparable for cost, the monotherapy regimen was the most expensive. The main determining factors for the choice of treatment of febrile neutropenic children, especially in a developing country, are cost, presence of indwelling catheter and the bacterial flora of the unit, as well as efficacy.     

Predictive Factors of Neutropenia in HIV-Infected Patients with Malignancy Receiving Chemotherapy or Radiotherapy

Objective: To determine the predictive factors of neutropenia in human immunodeficiency virus (HIV)-infected patients with malignancy receiving chemotherapy (CMT) or radiotherapy (RT). Materials and Methods: The author conducted a retrospective study on HIV-infected patients with malignancy receiving CMT or RT at Vajira Hospital, Navamindradhiraj University, Thailand, from January 1, 2013 to December 31, 2017. Baseline demographic characteristics, HIV disease data, and cancer data were collected. Results: A total of 210 courses of CMT, concurrent chemoradiation therapy (CCRT), or RT treatments were administered to 39 HIV-infected patients with malignancy. Neutropenia occurred in 51 (24.3%) of the 210 treatment courses in 23 (60%) patients. Multivariable analysis revealed that HIV-infected patients with malignancy who received CMT or CCRT (hazard ratio [HR] 10.83, 95% confidence interval [CI] 1.36–86.05, p = 0.024) and those who received over five cycles of CMT (HR 5.25, 95% CI 1.10–26.01, p = 0.037) were independently associated with neutropenia. Conclusion: Receiving CMT or CCRT and receiving more than five cycles of CMT are risk factors for neutropenia in HIV-infected patients with malignancy.     

Cost-Effectiveness Analysis of the Treatment of Ventilator-Associated Pneumonia with Linezolid or Vancomycin in Spain

Abstract

The aim of this study was to assess the cost-effectiveness of linezolid (LIN) versus vancomycin (VAN) for the treatment of ventilator-associated pneumonia (VAP) using a decision model analysis from the National Health System perspective. Patients and participants comprising four subgroups were analyzed: all, Gram-positive (GP), Staphylococcus aureus (SA), methicillin-resistant SA (MRSA). The treatments were LIN 600 mg i.v., every 12 hours, 10 days and VAN 1,000 mg i.v., every 12 hours 10 days. The primary outcome was the incremental cost-effectiveness of LIN in terms of cost per added quality-adjusted life year (QALY) gained. The secondary outcome was the marginal cost per year of life saved (LYS) generated by using LIN. Clinical cure and survival rates estimates were derived from a retrospective analysis of two trials comparing LIN with VAN. QALY was based on time-trade off study. Resource use and unit costs (€2003) were obtained from Spanish VAP treatment and health cost databases. The additional QALY and LYS per LIN patients were 0.392; 0.688; 0.606; 1.805 and 0.471; 0.829; 0.729; 2.175 respectively, compared with those of VAN in the patients with VAP (all, GP, SA, and MRSA, respectively). The additional costs for LYS with LIN, as compared to VAN were 1,501.31; 827.63; 955.13 and 289.51 €, respectively. The additional cost per QALY with LIN was 1,803.87; 997.25; 1,149.00 and 348.85 €, respectively. Conclusions: LIN was more cost-effective than VAN in the treatment of VAP in Spain, with an additional cost per QALY/LYS gained below the acceptable threshold in Spain of € 30,000 for new therapies.     

Symptom Frequency of Children with Cancer and Parent Quality of Life in Turkey

Background: This research was planned with the aim of determining the effect of symptom frequency ofchildren with cancer on the quality of life of their parents. Materials and Methods: In gathering the researchdata, the Child and Parent Information Form, the Symptom Evaluation Form and the Family Version of LifeQuality Scale in Cancer Patients were used. Evaluation was made by using percentage calculations, KruskalWallis test, Bonferroni adjusted t-test and Bonferroni adjusted Mann-Whitney U test. The significance levelwas accepted as 0.005. Results: Some 37.6% of the participant children were female and 62.4% were male, withan average age of 10.2±4.5. While 41.0% were newly diagnosed, 46.2% were in remission and 12.8% was inrelapse. Highly significant differences were detected according to the symptom frequency with parent physicaland psychological health, social anxiety, and spiritual wellness sub-dimensions, as well as total point averages.Conclusions: It is thought that following up the symptoms that might develop depending on cancer diagnosisand treatment and implementing nursing initiatives aimed at reducing the symptoms, knowing the importanceof life quality, maintaining measures aimed at life quality and planning initiatives to increase the life qualitywill play a key role in maintaining and developing the health of Turkish paediatric oncology patients and theirparents.     

卡培他滨单药或联合方案治疗乳腺癌骨转移的临床疗效观察

目的 探讨卡培他滨单药或联合伊班膦酸钠方案治疗乳腺癌骨转移的临床疗效.方法 选择乳腺癌骨转移患者106例作为研究对象,根据随机信封抽签原则分为观察组与对照组各53例,对照组给予卡培他滨单药治疗,观察组在对照组治疗的基础上联用伊班膦酸钠治疗.结果 治疗后观察组与对照组总有效率分别为86.8%和69.8%,观察组总有效率明显高于对照组(P<0.05).观察组随访1年、2年、3年的生存率分别为90.6%、77.4%和49.1%,都明显高于对照组的79.2%、50.9%和20.8%(P<0.05).治疗后观察组与对照组的骨痛NRS评分分别为(1.43±0.84)分和(2.53±1.21)分,都明显低于治疗前的(6.93±2.01)分和(6.91±2.13)分(P<0.05),治疗后观察组的骨痛NRS评分也明显低于对照组(P<0.05).结论 相对于卡培他滨单药方案,卡培他滨联合伊班膦酸钠方案治疗乳腺癌骨转移能有效降低骨痛,提高治疗疗效,从而延长患者的生存期,有很好的应用价值.     

替吉奥单药治疗老年或体弱转移性结直肠癌患者疗效分析

目的 观察分析替吉奥单药作为老年或体弱转移性结直肠癌(mCRC)患者治疗方案的疗效和毒副反应.方法 24例老年或体弱mCRC患者接受口服替吉奥治疗,即替吉奥35 mg·m-2,每天2次,连用2周,停药1周.观察其近期疗效、疾病无进展生存期、总生存期、毒副反应等.结果 全组24例患者的总有效率为16.7％,疾病控制率为75.0％;中位无进展生存期为4.1(95％CI为2.8 ～5.4)个月,中位总生存期:12.3(95％CI为9.9 ～14.7)个月;主要毒副反应为胃肠道反应、骨髓抑制,多为轻度,无患者因毒副反应终止治疗.结论 替吉奥单药治疗老年或体弱mCRC患者安全性高、疗效好.     

Comparison of Peripheral Blood Stem Cells Mobilized with Granulocyte Colony-stimulating Factor with or without Prior Standard-dose Chemotherapy in Patients with Malignancy

We studied the effect of granulocyte colony-stimulating factoron the magnitude of peripheral blood stem cell mobilizationin patients with malignancy. The leukapheresis products mobilizedwith granulocyte colony-stimulating factor alone at a steadystate (a period of full hematopoietic recovery) (group 1) werecompared with those obtained after cytotoxic chemotherapy usinggranulocyte colony-stimulating factor (group 2). In group 1,six patients underwent six courses of stem cell collection witha median of 20 l leukapheresis. In group 2, 10 patients underwent12 courses of stem cell collection with a median of 10 l leukapheresis.Median yields of group 1 vs. group 2 were mononuclear cells(x10⁹), 21.9 vs. 11.6; CD34⁺ cells (x10⁶/l), 14.5 vs. 17.1;colony-forming unit for granulocyte-macrophage (/ml), 223 vs.1193; burst-forming unit for erythroid (/ml), 29 vs. 71; colony-formingunit for erythroid (/ml), 42 vs. 29; colony-forming unit formegakaryocyte (/ml), 26 vs. 59. While there were no statisticallysignificant differences in the number of CD34⁺ cells betweenthe two groups, granulocyte-macrophage-committed progenitorcells were more enriched in the apheresis products of group2. The correlation between CD34⁺ cells and colony-forming unitfor granulocyte-macrophage was poor. Our results demonstratethat granulocyte colony-stimulating factor can mobilize a sufficientnumber of progenitor cells into the peripheral blood for stemcell transplantation with or without prior chemotherapy.     

FDA Approval Summary: Olaparib Monotherapy or in Combination with Bevacizumab for the Maintenance Treatment of Patients with Advanced Ovarian Cancer

On December 19, 2018, the U.S. Food and Drug Administration (FDA) granted approval to olaparib monotherapy for first‐line maintenance treatment of BRCA‐mutated (BRCAm) advanced ovarian cancer and, on May 8, 2020, expanded the indication of olaparib to include its use in combination with bevacizumab for first‐line maintenance treatment of homologous recombination deficient (HRD)–positive advanced ovarian cancer. Both these approvals were based on randomized, double‐blind, placebo‐controlled trials. Approval for olaparib monotherapy was based on the SOLO‐1 trial, comparing the efficacy of olaparib versus placebo in patients with BRCAm advanced ovarian, fallopian tube, or primary peritoneal cancer after surgical cytoreduction and first‐line platinum‐based chemotherapy. Two companion diagnostic (CDx) tests were approved with this indication: BRACAnalysis CDx, for germline BRCA1/2 alterations, and FoundationOne CDx, for BRCA1/2 alterations in tissue specimens. Approval for olaparib in combination with bevacizumab was based on the results of the PAOLA‐1 trial that compared olaparib with bevacizumab versus placebo plus bevacizumab in patients with advanced high‐grade epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer after first‐line platinum‐based chemotherapy and bevacizumab. Myriad myChoice CDx was designated as a companion diagnostic device for use of olaparib plus bevacizumab combination for ovarian cancer associated with HRD‐positive status. Both trials demonstrated clinically meaningful improvements in progression‐free survival and favorable benefit‐risk profiles for the indicated populations. This article summarizes the FDA thought process and data supporting the approval of olaparib as monotherapy and in combination with bevacizumab for maintenance therapy in this setting.Implications for PracticeThese approvals represent the first poly (ADP‐ribose) polymerase inhibitor, alone or in combination with bevacizumab, approved in first‐line maintenance treatment of women with advanced ovarian cancer after cytoreductive surgery and chemotherapy. In patients with BRCA‐mutated tumors, olaparib monotherapy demonstrated a 70% reduction in the risk of disease progression or death compared with placebo, and olaparib in combination with bevacizumab demonstrated a 67% reduction in the risk of disease progression or death compared with bevacizumab alone in homologous recombination deficient–positive tumors. These approvals represent a major advance for the treatment of women with advanced ovarian cancer who are in complete or partial response after their initial platinum‐based chemotherapy.