Poor Performance Status Score Research Articles

Endoscopic retrograde cholangiopancreatography for bile duct stones in patients with a performance status score of 3 or 4.

BACKGROUNDAs the aging population grows worldwide, the rates of endoscopic retrograde cholangiopancreatography (ERCP) for common bile duct stones (CBDS) in older patients with a poor performance status (PS) have been increasing. However, the data on the safety and efficacy of ERCP for CBDS in patients with a PS score of 3 or 4 are lacking, with only a few studies having investigated this issue among patients with poor PS.AIMTo examine the safety and efficacy of ERCP for CBDS in patients with a PS score of 3 or 4.METHODSThis study utilized a retrospective multi-centered design of three institutions in Japan for 8 years to identify a total of 1343 patients with CBDS having native papillae who underwent therapeutic ERCP. As a result, 1113 patients with a PS 0-2 and 230 patients with a PS 3-4 were included. One-to-one propensity-score matching was performed to compare the safety and efficacy of ERCP for CBDS between patients with a PS 0-2 and those with a PS 3-4.RESULTSThe overall ERCP-related complication rates in all patients and propensity score-matched patients with a PS 0-2 and 3-4 were 9.0% (100/1113) and 7.0% (16/230; P = 0.37), and 4.6% (9/196) and 6.6% (13/196; P = 0.51), respectively. In the propensity score-matched patients, complications were significantly more severe in the group with a PS 3-4 than in the group with a PS 0-2 group (P = 0.042). Risk factors for complications were indications of ERCP and absence of antibiotics in the multivariate analysis. Therapeutic success rates, including complete CBDS removal and permanent biliary stent placement, in propensity score-matched patients with a PS 0-2 and 3-4 were 97.4% (191/196) and 97.4% (191/196), respectively (P = 1.0).CONCLUSIONERCP for CBDS can be effectively performed in patients with a PS 3 or 4. Nevertheless, the indication for ERCP in such patients should be carefully considered with prophylactic antibiotics.

First-line osimertinib for poor performance status patients with EGFR mutation-positive non-small cell lung cancer: A prospective observational study.

The clinical outcomes of poor performance status (PS) patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) who are treated with osimertinib as a first-line treatment have not been sufficiently evaluated. This study aimed to assess the efficacy and safety of osimertinib in chemotherapy-naive and poor PS (2 or more) patients with NSCLC harboring sensitive EGFR mutations. We assessed the clinical effects of osimertinib as a first-line treatment for patients with poor PS NSCLC with an exon 19 deletion or exon 21 L858R mutation in EGFR. All patients were administered osimertinib (80mg/day) as the initial treatment. Sixteen patients (nine women and seven men) who were treated between August 2018 and July 2021 were included in this study; their median age was 78years. The overall objective response rate was 56.3%. The median progression-free survival (PFS) of the entire patient population was 10.5months and the PS score improved in 8 of 16 patients (50%). The most common adverse event was acneiform rash (42%), followed by diarrhea (36%) and paronychia (36%); none of these were of grade ≥ 3. Interstitial lung disease occurred in 2 patients (12.5%); however, no treatment-related deaths occurred. Considering the findings of this study, osimertinib appears to be an effective and safe treatment option for patients with poor PS and advanced NSCLC harboring sensitive EGFR mutations. To obtain conclusive results, further studies with larger cohorts are warranted.

Effectiveness and safety of immunotherapy in NSCLC patients with ECOG PS score ≥2 – Systematic review and meta-analysis

BackgroundImmune checkpoint inhibitors (ICIs) are standard of care in advanced non-small cell lung cancer (NSCLC), however their status in patients with poor performance status (PS) is poorly defined. We aimed to evaluate the efficacy and safety of ICIs in NSCLC patients with PS ≥ 2. MethodsWe conducted a systematic review and meta-analysis of interventional and observational studies, which reported efficacy and safety data on ICIs in PS ≥ 2 comparing to PS ≤ 1 NSCLC patients. Efficacy endpoints included: Objective Response Rate (ORR), Disease-Control Rate (DCR), Overall Survival (OS), Progression-Free Survival (PFS). Safety endpoint was the incidence of severe (grade≥3) Adverse Events (AE). Random-effects model was applied for meta-analysis. Heterogeneity was assessed using I2. The review is registered on PROSPERO (CRD42020162668). FindingsSixty-seven studies (n = 26,442 patients) were included. In PS ≥ 2 vs. PS ≤ 1 patients, the pooled odds ratios were: for ORR 0.46 (95 %CI: 0.39−0.54, I2:0 %); for DCR 0.39 (95 %CI: 0.33−0.48, I2:50 %) and for AEs 1.12 (95 %CI: 0.84–1.48, I2:39 %). The pooled hazard ratio for PFS was 2.17 (95 %CI: 1.96–2.39, I2:65 %) and for OS was 2.76 (95 %CI: 2.43–3.14, I2:76 %). The safety profile was comparable regardless of the PS status. InterpretationPatients with impaired PS status are, on average, twice less likely to achieve a response when exposed to ICIs when compared with representative PS ≤ 1 population. For lung cancer patients treated with ICIs, the impaired PS is not only prognostic, but also predictive for response, while the safety profile is not affected. Prospective randomized studies are indispensable to determine whether poor PS patients derive benefit from ICIs.

International consensus on severe lung cancer-the first edition.

Lung cancer is one of the most prevalent and lethal cancers worldwide (1). The traditional treatments include surgery, chemotherapy, radiotherapy and interventional therapy. The survival of lung cancer patients has dramatically been prolonged in recent years with the availability of targeted therapies, antiangiogenic agents and immune checkpoint inhibitors (ICIs). Meanwhile, technologies for the molecular detection of lung cancer have also advanced rapidly: the detection of single driver genes has evolved to cover combined multi-gene analysis, and whole exome sequencing (WES) has increasingly been applied in the clinical setting. In addition, life support technologies, including ventilators, artificial liver, and artificial kidney as well as extracorporeal membrane oxygenation (ECMO), have further matured, providing powerful forms of life support for patients with various acute and critical diseases. However, most clinical studies have only enrolled patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores from 0 to 1, with few patients having PS scores of 2; patients with a PS score of 3 or 4 have been typically excluded. Therefore, due to the lack of high-quality evidence, supportive care is recommended for patients with a PS score of 3 to 4 in the current guidelines. In the real-world, however, approximately 25% of lung cancer patients present with PS score of 3 or 4 (2) or attain scores between 3 and 4 during the course of treatment. Certain patients with high PS scores can benefit from individualized anti-tumor treatment plus appropriate life-support techniques. In 2017, the Lung Cancer Research Team at the First Affiliated Hospital of Guangzhou Medical College & Institute of Respiratory Diseases for the first time pioneered the concept of “advanced severe lung cancer” (3) and argued that standardized therapy for chronic obstructive pulmonary disease (COPD) plus anti-tumor therapy can improve both quality of life and prognosis in patients with lung cancer combined with COPD. The authors also found that the early detection of lung cancer driver genes and timely targeted therapy can be successful in treating patients with advanced severe lung adenocarcinoma with a PS score of 4 (4). In 2019, the concept of advanced severe lung cancer was further developed in a featured article (5) that indicated “Advanced severe lung cancer: does not refer to end-stage lung cancer but rather to stage IIIB, IIIC and IV lung cancers with a PS score of 2–4, which can result from a variety of factors related to the disease itself or anti-tumor drugs and which are highly likely to benefit from the currently available systemic anti-tumor therapies”. In recent years, with the advances in lung cancer diagnosis and treatment techniques and life support technologies, more clinical studies have enrolled patients with a PS score of 2, and some real-world studies have enrolled patients with PS scores of 3–4. Even for patients with early-stage lung cancer, studies have shown that patients with poor PS scores and co-morbidities have a reduced chance of undergoing surgery and an increased mortality rate (6); nevertheless, survival benefit may still be obtained through surgical modifications combined with individualized and multidisciplinary treatment (7). Therefore, the concept of severe lung cancer should not be limited to advanced lung cancer, but applied to all lung cancer patients. In particular, due to the increase in treatment options as well as substantially prolonged survival, the majority of patients may have a PS score between 2 and 4 for a certain period of time due to a variety of reasons. How to provide timely and reasonable treatment for these lung cancer patients has become a critically important real-world research topic. Therefore, we invited lung cancer experts at home and abroad to consider this issue, and this group has reached the following consensus.

Poor performance status and brain metastases treatment: who may benefit from the stereotactic radiotherapy?

Poor Performance Status (PS) of cancer patients, defined as PS score 2-3, is an impediment for many drug- and irradiation-based treatments, supported by the trials that exclude subjects with PS < 1. Reports on the benefits of stereotactic radiotherapy (SRT) for brain metastases (BMs) in poor PS patients are scarce. We sought to review the characteristics and survival outcomes of this cohort, to assess who may benefit most from SRT. We retrospectively evaluated 73 patients with PS 2 or 3 (63 and 10 cases) treated with SRT for 150 BMs from 2012 to 2018. Patients' characteristics and post-SRT survival, stratified by concomitant systemic treatment (CST) were assessed using the Kaplan-Meier method (p-value < 0.05). Non-small cell lung cancer was the most frequent primary tumor. Extracranial metastases were present in 86.3% of patients. The median overall survival (mOS) after SRT was estimated as 6.0months (range 0.2-37.7), with 6- and 12-month survival rates of 51.0% and 21.0%, respectively. CST was administrated to 59.7% of patients (immunotherapy, target therapy or chemotherapy). Patients treated with CST presented larger mOS (6.7 vs. 4.4months for patients treated with SRT alone, p = 0.3), and better 6- and 12-month survival rates (59% and 24% vs. 37% and 18% in patients not treated with CST). Survival rate after SRT for BMs in poor performance patients, especially with PS 2, can justify SRT, in particular if an effective systemic treatment is available. Both SRT and CST should be more accessible for these patients in clinical practice.

Association of tumor mutation burden and epidermal growth factor receptor inhibitor history with survival in patients with metastatic stage III/IV non-small-cell lung cancer: A retrospective study

OBJECTIVES:Lung cancer is the leading cause of cancer-related deaths worldwide. However, factors associated with the survival of patients with advanced non-small-cell lung cancer (NSCLC) who received only hospice care are largely unclear. In this study, we aimed to determine the prognostic factors correlated with survival in patients with advanced NSCLC who had undergone hospice care only.METHODS:A total of 102 patients with recurrent stage III/IV NSCLC after traditional treatment failure were investigated. Survival was measured from the date of enrollment to December 2019 or the time of death. Tumor tissues were collected, and DNA sequencing was performed to identify somatic mutations. Data on clinical factors of patients were collected and analyzed by univariate and multivariate analyses. Overall survival analysis was conducted using the Kaplan-Meier method.RESULTS:The 6-month, 1-year, and 2-year overall survival rates of the 102 patients with metastatic NSCLC were 17.65%, 3.92%, and 0.98%, respectively. The median overall survival of the 102 patients was 3.15 months. Tumor location in the peripheral lung, epidermal growth factor receptor (EGFR) inhibitor history, low tumor mutation load, adenocarcinoma, and poor performance status score were associated with prolonged survival compared with tumor location in the central lung, no EGFR inhibitor history, high tumor mutation load, squamous cell carcinoma, and good performance status score (p=0.045, p=0.003, p=0.045, p=0.021, and p=0.0003, respectively). CONCLUSIONS:EGFR inhibitor treatment history and tumor mutation load are risk factors for the overall survival of patients with stage III/IV NSCLC who have undergone only hospice care. These results provide a critical clinical basis for further study of nontraditional anti-tumor responses induced by EGFR inhibitors.

Lazarus type response to immunotherapy in three patients with poor performance status and locally advanced NSCLC: a case series and literature review.

Immune checkpoint inhibitors (ICIs) have become the standard treatment for patients with advanced non-small cell lung cancer (NSCLC). However, the safety and efficacy of ICIs in severe advanced NSCLC patients with poor performance status (PS) are still unclear. In the current study, we report a retrospective case series of three critically ill NSCLC patients with poor PS treated with immunotherapy in our hospital, and discussed these cases with reference to the existing literature and guidelines. Before treatment, the Eastern Cooperative Oncology Group (ECOG) PS scores of all three patients were 4, while programmed cell death protein ligand-1 (PD-L1) was strongly expressed (over 50%). After initiating anti-programmed cell death 1 (PD-1)/PD-L1 agents, the PS score of the three patients improved rapidly to 0-1 in a short time. A Lazarus type response was observed in all patients. There were no grade 3-4 immune-related adverse events (irAEs) in any of the patients, and only one patient developed rash (grade 2 irAE) and hypothyroidism (grade 2 irAE). The best response across all three patients was partial response (PR). As of the latest follow-up date on June 10, 2020, two patients are still alive, with the other having died on January 14, 2020, whose progression-free survival (PFS) and overall survival (OS) were 11 and 16 months, respectively. Immunotherapy is still an effective and low-toxicity option for severe advanced NSCLC patients with poor PS. Lazarus type response may occur, especially in patients whose PD-L1 is strongly expressed (≥50%). However, a greater amount of real-world data or randomized clinical trials are needed in this setting.

Efficacy and safety of combined immunotherapy and antiangiogenic therapy for advanced non-small cell lung cancer: A two-center retrospective study

BackgroundThe synergistic effects of immunotherapy and antiangiogenic therapy in advanced non–small cell lung cancer (NSCLC) have been reported in both preclinical and clinical trials. Herein, we evaluated the preliminary efficacy and safety of combined immunotherapy and antiangiogenic therapy in patients with previously treated advanced NSCLC in a real-world setting. MethodsWe conducted a 2-center, retrospective study of previously treated advanced NSCLC patients who received any anti-programmed death-1 antibody combined with antiangiogenic agent between May 2018 and March 2020. ResultsIn total, 57 patients were included in this study, and the objective response rate and disease control rate were 19.3% and 63.2%, respectively. The median progression-free survival (PFS) was 4.2 months (95% confidence interval [CI]: 3.2–5.2 months). Bone metastases (odds ratio [OR] not available; P < .01) and ≥ 3 treatment lines (OR 6.8; 95% CI: 1.6–29.6; P < .05) were independent negative predictors of objective response. Additionally, liver metastases (hazard ratio [HR] 3.7; 95% CI: 1.6–8.5; P < 0.01), poor performance status score (PS) (HR 3.4; 95% CI: 1.6–7.5; P < 0.01) and ≥ 3 treatment lines (HR 3.5; 95% CI: 1.7–7.4; P < 0.01) were found to be negative predictors of PFS. Eighty-nine percent of the patients experienced an adverse event. ConclusionsMetastatic sites (bone and liver), ≥3 treatment lines and poor PS were potential negative predictors of the efficacy of immunotherapy combined with antiangiogenic therapy for treating NSCLC. Further investigations and randomized controlled trials are needed.

Development and validation of a claims-based approach to proxy ECOG performance status across ten tumor groups

To develop a claims-based prediction model of poor performance status (PS) in commercially insured and Medicare supplemental beneficiaries with cancer. Retrospective analysis was conducted of electronic medical records (EMR) from community oncology practices linked to MarketScan claims. Multivariable logistic regression predicted PS scores from the EMR using claims-based diagnostic and procedure codes. The study included 8442patients diagnosed with cancer from 2007 to 2015. Overall, 8.1% of patients had poor EMR-based PS. Bootstrapping results from the final model showed sensitivity and specificity of approximately 75% with a predicted probability cutpoint=0.078, c-statistic=0.821 and pseudo-R2 =0.25. Patients with poor PS can be identified in claims data. This prediction model enables future studies evaluating cancer treatments and outcomes to account for PS.

Pemetrexed clinical studies in performance status 2 patients with non-small cell lung cancer (Review).

Because poor performance status (PS) is an independent prognostic factor in non-small cell lung cancer (NSCLC), PS scores are widely used by oncologists to make treatment decisions. Advanced NSCLC patients with an Eastern Cooperative Oncology Group PS of 2 have poor prognoses and are frequently excluded from clinical trials. This article reviews the efficacy and safety of pemetrexed in this patient group. We identified English-language literature (through March 2015) involving completed and ongoing studies through searches of PubMed, meeting abstracts, ClinicalTrials.gov and the European Clinical Trials Register; search terms included ‘pemetrexed,’ ‘NSCLC’ and ‘PS2’. Only studies reporting ≥1 subset analysis of PS2 patients receiving pemetrexed were chosen. Our search identified a total of ten pemetrexed studies in PS2 patients. Eight studies included only chemonaive patients, one study included both chemonaive patients and patients with one prior chemotherapy regimen and one study included only patients with one prior regimen. In subset analyses in these studies, PS2 patients had worse outcomes than PS0-1 patients regardless of treatment. In a phase 3 study, chemonaive advanced NSCLC patients with PS2 receiving pemetrexed-carboplatin versus pemetrexed experienced improved overall survival [hazard ratio (HR)=0.62; P=0.001], progression-free survival (HR=0.46; P<0.001) and response (P=0.032). This review confirms the poorer outcomes in PS2 vs. PS0-1 patients. Although it is not an approved combination therapy, in clinical studies, PS2 patients treated with pemetrexed plus carboplatin as first-line therapy had improved response rates and survival. Additional research on PS2 patients is needed.

Bi-weekly docetaxel and 5-fluorouracil: an effective and feasible treatment for advanced gastric cancer with poor performance status.

Background: The survival benefits from cytotoxic chemotherapy have been demonstrated in advanced gastric cancer (AGC). A large proportion of AGC patients initially present poor performance status (PS); however, most of the clinical evidence comes from trials on patients with good PS. A better-designed regimen is greatly needed for AGC patients with poor PS.Objective: To evaluate the efficacy and safety of a modified combination regimen with docetaxel plus 5-fluorouracil (5-FU) every two weeks as first-line treatment in AGC patients with poor PS.Methods: From September 2011 to December 2013, 12 patients diagnosed with AGC with Eastern Cooperative Oncology Group (ECOG) PS scores of 3 or 4 were included in this study. All the patients received docetaxel 60 mg/m2 on Day 1, 5-FU 400 mg/m2 intravenous (i.v.) bolus on Day 1, and a 46-hour continuous i.v. infusion of 5-FU 2400 mg/m2 every two weeks, until disease progressed or patients experienced unacceptable toxicity or declined treatment. Detailed clinical, pathologic and survival data were all recorded.Results: Eleven out of 12 patients were assessable for responses, whereas nine cases (75%) achieved partial response, one (8.3%) achieved stabilized disease, and one (8.3%) had progressive disease. The median progression-free survival was 6.5 months (95% CI: 4.8–8.2). The median overall survival was 12.0 months (95% CI: 9.0–15.0). The most common Grade 3/4 toxicities were anemia in seven patients (58.3%). No patient experienced febrile neutropenia.Conclusion: The novel modification of bi-weekly docetaxel and 5-FU is a promising treatment option for AGC with poor PS, showing great efficacy and acceptable toxicity.

Validation and Reliability Testing of the EORTC QLQ-NMIBC24 Questionnaire Module to Assess Patient-reported Outcomes in Non–Muscle-invasive Bladder Cancer

BackgroundWell-developed and well-tested patient-reported outcome measures for non–muscle-invasive bladder cancer (NMIBC) are required. ObjectiveTo test and adapt the scale structure and explore the psychometric properties of the European Organisation for Research and Treatment of Cancer (EORTC) questionnaire for NMIBC. Design, setting, and participantsA total of 433 patients in the Bladder COX-2 Inhibition Trial (BOXIT) completed the EORTC QLQ-C30 and NMIBC questionnaires. BOXIT is evaluating the addition of celecoxib to standard treatment in high- and intermediate-risk NMIBC. Outcome measurements and statistical analysisMultitrait scaling investigated and adapted the questionnaire scale structure and evaluated the reliability and validity of the revised scales, as well as responsiveness to change. Results and limitationsA total of 410 patients (94.7%) (79.3% men, 74.6% high risk) returned baseline forms, and the questionnaire response rate was 88.2%. Multitrait scaling confirmed six scales and five single items. Scales and items demonstrated significant differences between patients with good and poor performance status scores (p<0.001). Men reported better sexual function than women (p<0.001). Scale and single-item module scores were not highly correlated with QLQ-C30 scores (evidence of discriminant validity), and the module was responsive to changes in health over time. International and test–retest data are required. ConclusionsThis study demonstrates the evidence-driven adapted scale structure and psychometric data of the EORTC QLQ-NMIBC24 module to use in clinical trials of patients with high- or intermediate-risk bladder cancer.

TOPICAL: Randomized phase III trial of erlotinib compared with placebo in chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC) and unsuitable for first-line chemotherapy.

7504 Background: Poor performance status (PS) NSCLC is an important, under-studied group of lung cancer patients, affecting 30-40% of patients. We determined the role of erlotinib plus best supportive care (BSC) in chemo-naïve, poor PS advanced NSCLC patients. Methods: Chemo-naïve NSCLC patients (ECOG PS 2/3 or PS 0/1 unfit for platinum chemotherapy; stage IIIB/IV) were randomized to erlotinib (150 mg/d) plus BSC (n = 350) or placebo plus BSC (n = 320). Endpoints were overall survival (OS), progression-free survival (PFS), response rate, and toxicity. The trial had 90% power to detect an increase in 1-year OS from 10% to 17.5%. Results: Between 2005 and 2009, 670 patients were randomised to either erlotinib (350) or placebo (320), from 78 UK centres. Median age was 77 yrs (range 42-91); 61% male; 38% adenocarcinoma, 39% squamous histology; the % with ECOG PS score of 0/1, 2 and 3 were 16%, 55% and 29% respectively; 35% stage IIIB and 65% stage IV disease. Baseline patient characteristics were balanced between the groups. At the time of analysis, 559 patients had died. Hazard ratio (HR; erlotinib vs placebo) for OS was 0.98 [95% CI 0.82-1.15; p = 0.77]. PFS HR was 0.86 [0.74-1.01, p = 0.07]. Pre-specified subgroup analyses showed significant longer OS and PFS for females only: HR of 0.75 [0.57-0.99, p = 0.04] and 0.64 [0.49-0.83, p = < 0.001] respectively. PFS HR for adenocarcinoma was 0.74 [0.57-0.97, p = 0.03]. PFS HR according to gender and histology were: 0.68 [0.46-0.99, p = 0.046] females with adenocarcinoma; 0.62 [0.43-0.89, p = 0.01] females with non-adenocarcinoma; 0.85 [0.59-1.22, p=0.37] males with adenocarcinoma; and 1.14 [0.89-1.45, p = 0.31] male with non- adenocarcinoma. As expected, increased Grade 3/4 rash and diarrhoea were observed in patients receiving erlotinib. Conclusions: Overall, erlotinib plus BSC did not improve OS, but there was some evidence of benefit for PFS. However, there was a clear effect on both OS and PFS for females, and PFS for adenocarcinoma. However, the effect in adenocarcinoma was largely driven by female patients. Final analyses, including EGFR mutation, VeriStrat serum tests and QoL will be presented. No significant financial relationships to disclose.

Efficacy of Lower Dose Capecitabine in Patients with Metastatic Breast Cancer and Factors Influencing Therapeutic Response and Outcome

Capecitabine exerts considerable therapeutic efficacy in metastatic breast cancer (MBC) patients previously treated with anthracyclines and taxanes. In this study, the efficacy and safety of lower dose capecitabine (2000 mg/m(2)/d) in patients with anthracycline- and taxane-pretreated MBC were studied with a special emphasis on the potential predictors of time to tumor progression (TTP) and response to the capecitabine treatment. The overall response rate (ORR) was 17%. The median TTP was 5 months. Among various factors analyzed, univariate analysis showed that a performance status (PS) of 2 and the presence of visceral metastases were inversely correlated with TTP. Multivariate analysis showed that a poor PS score was associated with impaired TTP. Our study indicates that lower dose capecitabine has substantial antitumor activity and a favorable safety profile in the treatment of anthracycline- and taxane-pretreated MBC. Also, only performance score was demonstrated to be a significant parameter affecting TTP.

Optimizing First-Line Treatment Options for Patients with Advanced NSCLC

The median survival time for advanced non-small cell lung cancer (NSCLC) remains poor, despite years of research into new chemotherapy combinations. Platinum-based chemotherapy has long been the standard of care for the initial treatment of advanced NSCLC. While no one particular platinum-based chemotherapy regimen is definitely superior to the others (as demonstrated in the Eastern Cooperative Oncology Group's E1594 trial), three randomized phase III trials (the Southwest Oncology Group 9509, Italian Lung Cancer Project, and TAX326 trials) have recently demonstrated that taxane-platinum doublets are better tolerated than a combination of vinorelbine and cisplatin (VC). Moreover, a combination of docetaxel and cisplatin produced superior survival and quality of life than VC in the TAX326 study. Nonplatinum combinations, such as a taxane-gemcitabine doublet, appear promising and better tolerated than their platinum-based comparators in other studies. Efforts to evaluate chemotherapy specifically in elderly patients and in those with poor performance status (PS) have increased. Single-agent chemotherapy has been safely administered to these populations, but platinum-based doublet therapy may also be feasible in both elderly patients and patients with PS scores of 2. The addition of the monoclonal antibody against vascular endothelial growth factor, bevacizumab, to standard chemotherapy for patients with non-squamous cell advanced NSCLC significantly extended median survival in the E4599 randomized trial. Each incremental advance demonstrates that progress can be made in first-line treatment of advanced NSCLC.

Topotecan in the treatment of relapsed small cell lung cancer patients with poor performance status.

Topotecan is the only single-agent therapy approved by the U.S. Food and Drug Administration for the treatment of patients with recurrent small cell lung cancer (SCLC). Poor performance status (PS) at the time of relapse can hinder the ability of a patient to tolerate second-line chemotherapy. To investigate the feasibility of topotecan in the treatment of relapsed SCLC patients with PS 2 scores, we retrospectively analyzed data from five clinical trials that included 479 patients who were treated with single-agent topotecan at a dose of 1.5 mg/m2/day on days 1-5 of a 21-day course. Of these patients, 381 had a PS 0 or 1 and 98 had a PS 2. Topotecan was well tolerated by both patient groups. Hematologic toxicities were generally manageable, and neutropenia was noncumulative. With the exception of grade 3/4 anemia, the incidences of severe hematologic toxicities were not statistically different between the two groups. The nonhematologic toxicity profiles were also similar in the two patient groups. Treatment provided similar benefits, including antitumor response rates and symptom palliation, in PS 0/1 and PS 2 patients. As expected, the median overall survival time was shorter in patients with worse PS scores; the median overall survival times were 36.3 weeks, 25.4 weeks, and 16 weeks for PS 0, PS 1, and PS 2 patients, respectively. In conclusion, treatment with topotecan is feasible and well tolerated in patients with relapsed SCLC with suboptimal PS scores.