Redefining Quality Measurement in Cancer Care.

Quality measurement in oncology is increasing in significance as payment schemes shift from volume to value. As demand for quality measures increases, challenges in the development of quality measures, standardization across measures, and the limitations of health information technology have become apparent. Moreover, the time and financial burden associated with developing, tracking, and reporting quality measures are substantial. Despite these challenges, best practices and leaders in the field of quality measurement in oncology have emerged. To understand the current challenges and promising practices in quality measurement and to explore future considerations for measure development and measure reporting in oncology, NCCN convened the NCCN Policy Summit: Redefining Quality Measurement in Oncology. The summit included discussion of the current quality landscape and efforts to develop quality measures, use of quality measures in various programs, patient perspective of quality, and challenges and best practices for quality reporting.

Docetaxel or pemetrexed with or without cetuximab in recurrent or progressive non-small-cell lung cancer after platinum-based therapy: a phase 3, open-label, randomised trial.

BACKGROUND: Available preclinical and phase 2 clinical data suggest that the addition of cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor (EGFR), to chemotherapy might improve outcome in patients with advanced non-small-cell lung cancer (NSCLC). We aimed to assess whether the addition of cetuximab to chemotherapy improved progression-free survival in patients with recurrent or progressive NSCLC after platinum-based therapy. METHODS: In this unmasked, open-label randomised phase 3 trial we enrolled patients with metastatic, unresectable, or locally advanced NSCLC from 121 sites in Canada and the USA. Eligible patients were those aged 18 years or older who had experienced progressive disease during or after one previous platinum-based regimen. Initially, patients were randomly assigned to receive either pemetrexed (500 mg/m(2)) or docetaxel (75 mg/m(2)) and then randomly assigned within each group to receive their chemotherapy with or without cetuximab (400 mg/m(2) at first dose and 250 mg/m(2) weekly thereafter) until disease progression or unacceptable toxicity. However, after a change in the standard of care, investigators chose whether to treat with pemetrexed or docetaxel on a patient-by-patient basis. The primary analysis was changed to compare progression-free survival with cetuximab plus pemetrexed versus pemetrexed, on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT00095199. FINDINGS: Between Jan 10, 2005, and Feb 10, 2010, we enrolled 939 patients; data for one patient was accidentally discarded. Of the remaining 938 patients, 605 received pemetrexed (301 patients with cetuximab and 304 alone) and 333 received docetaxel (167 in combination with cetuximab and 166 alone). Median progression-free survival with cetuximab plus pemetrexed was 2·9 months (95% CI 2·7-3·2) versus 2·8 months (2·5-3·3) with pemetrexed (HR 1·03, 95% CI 0·87-1·21; p=0·76). The most common grade 3-4 adverse events with cetuximab plus pemetrexed were fatigue (33 [11%] of 292 patients), acneiform rash (31 [11%]), dyspnoea (29 [10%]), and decreased neutrophil count (28 [10%]), and with pemetrexed alone were dyspnoea (35 [12%] of 289 patients), decreased neutrophil count (26 [9%]), and fatigue (23 [8%]). A significantly higher proportion of patients in the cetuximab plus pemetrexed group (119 [41%] of 292 patients) experienced at least one serious adverse event than those patients in the pemetrexed group (85 [29%] of 289 patients; p=0·0054). Nine (3%) of 292 treated patients in the cetuximab and pemetrexed group died of adverse events compared with five (2%) of 289 treated patients in the pemetrexed alone group. INTERPRETATION: The use of cetuximab is not recommended in combination with chemotherapy in patients previously treated with platinum-based therapy. FUNDING: Eli Lilly and Company and ImClone Systems LLC, a wholly owned subsidiary of Eli Lilly and Company.

Closing the Testing Gap: Standardization of Comprehensive Biomarker Testing for Metastatic Non-Small-Cell Lung Cancer in a Large Community Oncology Practice.

PURPOSE: Non-small-cell lung cancer (NSCLC), the leading cause of cancer death in the United States, accounts for 85% of all lung cancer cases. Biomarker testing is an integral part of the care of patients with NSCLC. Despite broad consensus recommendations that all patients with metastatic NSCLC (mNSCLC) undergo comprehensive biomarker testing (comprehensive genomic profiling and PD-L1), testing rates remain suboptimal. METHODS: The primary goal of this project was to apply National Comprehensive Cancer Network (NCCN) guidelines for comprehensive biomarker testing to all new patients with mNSCLC within a large community practice. Plan-Do-Study-Act methodology was used, with cycle 1 focused on provider education and the creation of a mNSCLC initial consult Note (electronic health record template/McKesson iKnowMed G2) and accompanying order set. Staging, template/order set utilization, and comprehensive biomarker testing rates were recorded while workflow processes were monitored. Cycle 2 centered on improved cancer staging, data analytic reporting, auditing, and reeducation. RESULTS: The comprehensive biomarker testing rates increased from a historic rate of 68% to 92.7% during the 1-year intervention period. The template utilization rate was 71% with complete staging (TNM stage and relevant biomarkers) documented in 40%. CONCLUSION: Implementation and standardization of comprehensive biomarker testing of patients with mNSCLC in a large multisite community-based oncology practice is feasible and results in significant improvement in comprehensive biomarker testing and reporting. Establishing reliable and measurable tracking metrics to ensure that these new processes are used and maintained can assist in scaling these processes. Efforts to scale this best practice are planned across the US Oncology Network.

Target-specific, histology-independent, randomized discontinuation study of lapatinib in patients with HER2-amplified solid tumors.

BACKGROUND: To explore the activity of lapatinib with a novel trial design focused on the drug target rather than on histology. METHODS: Patients with HER2 amplified gastro-esophageal, bladder, ovarian, or uterine tumors were enrolled into a double-blinded randomized discontinuation study of lapatinib 1,500 mg PO daily. The planned sample size was 250 patients with HER2 amplified tumors, with the goal of randomizing 100 patients with stable disease (SD) at week 12 to either lapatinib or placebo. Patients responding after 12 weeks continued on lapatinib; those who progressed were discontinued from study. The primary objectives were response rate after 12 weeks and the percentage of patients who remained progression free 12 weeks after randomization to placebo versus lapatinib. Secondary objectives were duration of response and determination of the incidence of HER2 amplification in multiple tumor types. RESULTS: A total of 141 patients were screened and 32 patients with HER2 amplified tumors were enrolled. At week 12, 1 (3%) patient had a complete response, 9 (28%) had stable disease, 20 (63%) had progressive disease, and 2 (6%) were unknown. Only 7 patients with SD underwent randomization. The low response rate coupled with slow screening and enrollment led to early study closure. CONCLUSIONS: Basing trial eligibility on the presence of a genetic target, versus histologic classification, is challenging. While HER2 amplifications appear to be prevalent in select non-breast tumors, lapatinib monotherapy is associated with modest activity. The target-specific histology-independent randomized discontinuation design still merits consideration for targets clearly implicated in "oncogene addiction".

Biomarker testing and tissue journey among patients with metastatic non-small cell lung cancer receiving first-line therapy in The US Oncology Network.

OBJECTIVES: The MYLUNG (Molecularly Informed Lung Cancer Treatment in a Community Cancer Network) consortium pragmatic study assessed real-world biomarker testing rates and turnaround times within a large community-based oncology network. MATERIALS AND METHODS: This retrospective observational chart review study investigated patients with mNSCLC initiating first-line (1L) systemic therapy between 01-April-2018 and 31-March-2020. Biomarker testing rates and timing relative to 1L therapy for EGFR, ALK, ROS1, BRAF, and PD-L1 were assessed, including use of next-generation sequencing (NGS). RESULTS: Among 3474 adults: 74% had adenocarcinoma and 76% had a documented ECOG performance status of 0 or 1. Ninety percent had testing for at least one biomarker, and 46% received all 5 biomarker tests. Changes in testing rates from 2018 to 2020 were 71% to 71% for EGFR, 71% to 70% for ALK, 69% to 67% for ROS1, 51% to 59% for BRAF, 82% to 84% for PD-L1, and 42% to 49% for all 5 biomarkers. NGS testing increased from 33% to 45% (p < 0.0001). Median time from mNSCLC diagnosis to 1L therapy was 35 days. Median turnaround times from biomarker testing orders to results ranged from 10 to 15 days for the individual biomarkers and 18 days for NGS. CONCLUSION: In this real-world study, while most patients received at least one biomarker test prior to 1L, <50% received all 5 tests. NGS testing also occurred in < 50% of patients but appeared to increase over time. The next phase of MYLUNG will evaluate contemporary ordering practices and turnaround times prospectively.

Telemedicine in Community Cancer Care: How Technology Helps Patients With Cancer Navigate a Pandemic.

COVID-19 places unprecedented demands on the oncology ecosystem. The extensive pressure of managing health care during the pandemic establishes the need for rapid implementation of telemedicine. Across our large statewide practice of 640 practitioners at 221 sites of service, an aggressive multidisciplinary telemedicine strategy was implemented in March by coordinating and training many different parts of our healthcare delivery system. From March to September, telemedicine grew to serve 15%-20% of new patients and 20%-25% of established patients, permitting the practice to implement safety protocols and reduce volumes in clinic while continuing to manage the acute and chronic care needs of our patient population. We surveyed practice leaders, queried for qualitative feedback, and established 76% were satisfied with the platform. The common challenges for patients were the first-time use and technology function, and patients were, in general, grateful and happy to have the option to visit their clinicians on a telemedicine platform. In addition to conducting new and established visits remotely, telemedicine allows risk assessments, avoidance of hospitalization, family education, psychosocial care, and improved pharmacy support. The implementation has limitations including technical complexity; increased burden on patients and staff; and broadband access, particularly in rural communities. For telemedicine to improve as a solution to enhance the longitudinal care of patients with cancer, payment coverage policies need to continue after the pandemic, technologic adoption needs to be easy for patients, and broadband access in rural areas needs to be a policy priority. Further research to optimize the patient and clinician experience is required to continue to make progress.

Uncertainty from COVID-19 delays progress on the road to value-based cancer care.

COVID-19 has created a significant distraction from normal practice operations. The uncertainty that comes along with the pandemic is a huge worry, and can distract from practice transformation.

Evaluation of Practice Patterns Among Oncologists Participating in the Oncology Care Model.

Importance: Health insurers reimburse clinicians in many ways, including the ubiquitous fee-for-service model and the emergent shared-savings models. Evidence on the effects of these emergent models in oncological treatment remains limited. Objectives: To analyze the early use and cost associations of a recent Medicare payment program, the Oncology Care Model (OCM), which included a shared savings-like component. Design, Setting, and Participants: This nonrandomized controlled study used a difference-in-differences approach on 2 years of data, from July 1, 2015, to June 30, 2017-1 year before and 1 year after launch of the OCM-to compare the differences between participating and nonparticipating practices, controlling for patient, clinician, and practice factors. Participation in the OCM began on July 1, 2016. Associations of participation with care use and cost were estimated for care directly managed by clinicians from a large network within their Medicare populations for breast, lung, colon, and prostate cancers. Data were analyzed from September 2019 to March 2020. Exposures: Participating practices were paid a monthly management fee of $160 per beneficiary and a potential risk-adjusted performance-based payment for eligible patients who received chemotherapy treatment, in addition to standard fee-for-service payments. Main Outcomes and Measures: Office visits, drug administrations, patient hydrations, drug costs, and total costs. Results: Monthly means data at the physician-level were evaluated for 11 869 physician-months for breast cancers, 11 135 physician-months for lung cancers, 8592 physician-months for colon cancers, and 9045 physician-months for prostate cancers. Patients at OCM practices had a mean (SD) age of 63.4 (3.1) years, and a mean (SD) of 59% (7 percentage points) of their patients were women. Participation in the OCM was associated with less physician-administered prostate cancer drug use (difference, 0.29 [95% CI, -0.47 to -0.11] percentage points, or 24.0%) translating to a mean of $706 (95% CI, -$1383 to -$29) less in drug costs per month. Monthly drug costs were also lower, at $558 (95% CI, -$1173 to $58) less for treatment for lung cancer. Total costs were lower by 9.7% or $233 (95% CI, -$495 to $30) for breast cancer, 9.9% or $337 (95% CI, -$618 to -$55) for lung cancer, 14.2% or $385 (95% CI, -$780 to $10) for colon cancer, and 29.2% or $610 (95% CI, -$1095 to -$125) for prostate cancer; however, these differences were largely offset by program costs. Clinician visits were also lower by 11.2% or 0.11 (95% CI, -0.20 to -0.01) percentage points among patients with breast cancer and by 14.4% or 0.19 (95% CI, -0.37 to -0.02) among patients with colon cancer. Conclusions and Relevance: These findings suggest that payment models with shared-savings components can be associated with fewer visits and lower costs in certain cancer settings in the first year, but the savings can be modest given the costs of program administration.

Hospice or Hospital: The Costs of Dying of Cancer in the Oncology Care Model.

Background: End-of-life management is a difficult aspect of cancer care. With the oncology care model (OCM), we have data to assess both clinical outcomes and total cost of care (TCOC). Objective: To measure and characterize the TCOC for those who received less than three days of hospice care (HC) at the end of life compared with those who received three days or more. Design: Assess data on costs and site and date of death from Medicare claims on patients identified in the OCM who received chemotherapy in the six months before death. Standard statistical methods were used to characterize both populations. Setting/Subjects: Subjects were Medicare patients with cancer who died while managed by U.S. oncology practices in the OCM. Measurements were TCOC in 30-day intervals for the last months of life, cost by site of care at the end of life, and demographic characteristics of the population and association with HC. Results: There were 7329 deaths. Dying in the hospital was twice the cost of dying at home under HC ($20,113 vs. $10,803). Of demographic groups measured, only black race and a lymphoma diagnosis had <50% hospice enrollment for three days or more before death. Conclusions: This study reinforces previous studies regarding costs in the last 30 days of life. The graphic representation highlights the dollar cost and the costs of lost opportunity. Using these data to improve communication, addressing socioeconomic support, and formal palliative care integration are potential strategies to improve care.

The Centers for Medicare & Medicaid Services Oncology Care Model Halfway Through: Perspectives from Diverse Participants.

The Oncology Care Model (OCM) is a 5-year model developed and tested by the Centers for Medicare & Medicaid Services that uses an episode-based payment model triggered by the receipt of chemotherapy to test if changing payment mechanisms, in conjunction with a requirement for enhanced patient services, can generate clinical transformation that will orient practices toward more patient-centered, high-value care to reduce expenditures and preserve or enhance quality of care for beneficiaries. The model is geographically diverse with practices in 34 states and encompasses practices ranging in size from 1 to more than 400 practitioners, with a multitude of business structures. Given these varied clinical and business environments, we believe that OCM-participating practices will have different opportunities and challenges as they work toward practice transformation, but they will likely share similarities with other practices in similar clinical and business settings. This commentary shares the experiences of four diverse groups participating in OCM-three practices and one network of practices-halfway through the model's projected 5-year life cycle in the expectation that these experiences will be of value to other practices embarking toward patient-centered, high-value practice transformation.

Three-Year Results of a Medicare Advantage Cancer Management Program.

PURPOSE: Reform of cancer care delivery seeks to control costs while improving quality. Texas Oncology collaborated with Aetna to conduct a payer-sponsored program that used evidence-based treatment pathways, a disease management call center, and an introduction to advance care planning to improve patient care and reduce total costs. METHODS: From June 1, 2013, to May 31, 2016, 746 Medicare Advantage patients with nine common cancer diagnoses were enrolled. Patients electing for patient support services were telephoned by oncology nurses who assessed symptoms and quality of life and introduced advance care planning. Shared cost savings were determined by comparing the costs of drugs, hospitalization, and emergency room use for 509 eligible patients in the study group with a matched cohort of 900 Medicare Advantage patients treated by non-Texas Oncology providers. Physician adherence to treatment pathways and performance and quality metrics were evaluated. RESULTS: During the 3 years of the study, the cumulative cost savings were $3,033,248, and savings continued to increase each year. Drug cost savings per patient per treatment month were $1,874 (95% CI, $1,373 to $2,376; P < .001) after adjusting for age, diagnosis, and study year. Solid tumors contributed most of the savings; hematologic cancers showed little savings. For years 1, 2, and 3, adherence to treatment pathways was 81%, 84%, and 90%, patient satisfaction with patient support services was 94%, 93%, and 94%, and hospice enrollment was 55%, 57%, and 64%, respectively. CONCLUSION: A practice-based program supported by a payer sponsor can reduce costs while maintaining high adherence to treatment pathways and patient satisfaction in older patients.

Ixabepilone and Carboplatin for Hormone Receptor Positive/HER2-neu Negative and Triple Negative Metastatic Breast Cancer.

BACKGROUND: Hormonal therapies and single-agent sequential chemotherapeutic regimens are the standards of care for HER2- metastatic breast cancer (MBC). However, treating patients with hormone-refractory and triple negative (TN) MBC remains challenging. We report the results of combined ixabepilone and carboplatin in a single-arm phase II trial. PATIENTS AND METHODS: In the present prospective analysis of hormone receptor-positive (HR+)/HER2- and TN MBC cohorts, patients could have received 0 to 2 chemotherapy regimens for MBC before enrollment. All patients received ixabepilone 20 mg/m2 and carboplatin (area under the curve, 2.5) on days 1 and 8 every 21 days. The primary endpoint was the objective response rate (ORR). The secondary objectives included progression-free survival (PFS), clinical benefit rate (CBR), overall survival (OS), and toxicity. RESULTS: We enrolled 54 HR+ and 49 TN patients (median, 1 previous chemotherapy regimen for metastatic disease; most in addition to adjuvant chemotherapy). The ORR was 34% and 30.4% for the HR+ and TN patients, respectively, with a corresponding CBR of 56.6% and 41.3%. The ORRs were similar in taxane-pretreated patients (ORR, 31.4% and 28.6% for HR+ and TN patients, respectively). The median OS was 17.9 months for HR+ patients and 12.5 months for TN patients. The median PFS was similar for both groups at 7.6 months. Grade 3/4 nonhematologic toxicities included neuropathy (9%) and fatigue (8%). Nine patients developed grade 3/4 neuropathy, 7 of whom had received previous taxane treatment. CONCLUSION: Ixabepilone plus carboplatin is active even in later-line HR+ and TN disease. Toxicities were manageable without cumulative myelosuppression. This combination is a reasonable option for those patients with MBC who require combination chemotherapy.

Prognostic factors in stage III non-small-cell lung cancer.

PURPOSE: The aim of this study is to present an analysis investigating the association of patient characteristics with overall survival (OS) in individuals with stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Ten prognostic factors were analyzed in 203 patients with NSCLC who were enrolled in a phase III trial conducted by the Hoosier Oncology Group and US Oncology between 2002 and 2006. Eligible patients had untreated stage III NSCLC, forced expiratory volume in one second (FEV(1)) > or = 1 liter, baseline performance status of 0/1, and weight loss < 5% in 3 months preceding the trial. Univariate analysis, Cox proportional hazards regression, and parametric accelerated failure time models were performed to identify the factors that affected survival duration. Variables analyzed included age (< 70 years vs. > or = 70 years), sex, ethnicity, body mass index, performance status (0 vs. 1), FEV(1) (> 2 L vs. 1-2 L), smoking status (current vs. never/former), hemoglobin (Hb) level, use of positron emission tomography scan in staging, and stage (IIIA vs. IIIB). RESULTS: Median follow-up was 25.6 months and the median OS was 21.2 months. The univariate analysis showed that Hb levels > or = 12 were associated with an improved survival (P = .033). The multivariable parametric accelerated failure time model demonstrated the association of FEV(1) > 2 L (P = .014), and higher pretreatment Hb values (P = .007) as independent prognostic factors for OS. Similarly in the Cox regression, survival was influenced by Hb and FEV(1) > 2 L. CONCLUSION: This analysis suggests that FEV(1) > 2 L and higher pretreatment Hb values are associated with improved OS in patients with stage III NSCLC. These factors can be useful in predicting for more favorable outcomes in patients with stage III NSCLC and provide additional information when designing future studies.

Phase II trial of docetaxel/capecitabine in hormone-refractory prostate cancer.

BACKGROUND: Docetaxel is the most active single agent in the treatment of hormone-refractory prostate cancer (HRPC). Because of the preclinical and clinical evidence of synergy of capecitabine and docetaxel, it was hypothesized that this combination would be active and tolerable in HRPC. PATIENTS AND METHODS: Patients received docetaxel 60 mg/m2 intravenously over 60 minutes on day 1 of each 21-day cycle and capecitabine 1000 mg/m2 administered orally twice daily on days 1-14 of each cycle for a maximum of 8 cycles or until disease progression or intolerable toxicity. Seventy-seven patients were enrolled at 43 US Oncology sites. The median age was 69.3 years (range, 48-86 years); 86% were white, and the Eastern Cooperative Oncology Group performance status scores of 0 and 1 were 49% and 51% respectively. Sixty-nine (90%) patients were evaluated for prostate-specific antigen response. RESULTS: Overall, 41% of patients had a decreased prostate specific antigen level > or = 50%. There were 4 complete responses (6%), 24 partial responses (35%), 29 incidences of stable disease (43%), and 11 incidences of progressive disease (16%). Nine patients has stable disease > or = 6 months and the clinical benefit rate was 54%. The median time to response was 1.5 months (range, 1-16.9 months). The estimated survival at 12 and 24 months (range, < 1-27 months). There were no treatment-related deaths. Grade 3/4 toxicities included neutropenia (50%), leukopenia (22%), hand-foot syndrome (17%), fatigue (11%), and nausea (11%). CONCLUSION: Docetaxel/capcitabine is an active and tolerable combination in HRPC. Toxicity was acceptable and anticipated. Response rate and survival are comparable with other docetaxel combinations.

Results of a phase II study of weekly paclitaxel plus carboplatin in patients with extensive small-cell lung cancer with Eastern Cooperative Oncology Group Performance Status of 2, or age > or = 70 years.

PURPOSE: To determine the 1-year survival, response rate (RR), time to progression (TTP), and safety of weekly paclitaxel plus carboplatin (PC) in patients with extensive small-cell lung cancer (ESCLC) with an Eastern Cooperative Performance Status performance status (PS) of 2 or an age > or = 70 years. PATIENTS AND METHODS: Patients were treated with PC (paclitaxel 80 mg/m(2) and carboplatin area under the curve = 2) by intravenous infusion on days 1, 8, and 15 of every 4-week cycle for up to six cycles. RESULTS: Between July 2000 and December 2001, 77 eligible patients (50.6% were male, 97.4% were white, 44.2% had PS of 2, with median age of 74 years) with ESCLC were enrolled. Among the 66 patients who were assessable for response, 25 responded to treatment (one complete response and 24 partial responses), for an objective RR of 38%. There were eight cases of stable disease (12.1%) and 33 cases of progressive disease (50%). The median survival was 7.2 months (range, < 1 to 24.4 months), and the estimated 1-year survival rate was 30%. The median TTP was 3.5 months (range, < 1 to 21.2 months), and the estimated 1-year progression-free survival rate was 8%. The median duration of response was 4.5 months (range, 1.6 to 17.5 months). One death (sepsis) was possibly related to the study drugs. Grades 3 and 4 toxicities experienced by > or = 5% of patients included neutropenia (22.1%), fatigue (8.6%), anemia (5.2%), and nausea/vomiting (5.2%). CONCLUSION: This regimen produced relatively few toxicities (only two of the 66 assessable patients received fewer than two cycles because of toxicity), and both the median and 1-year survival were similar to other regimens. This regimen may be a preferable treatment choice for patients with ESCLC who have a poor PS or who are aged > or = 70 years.

Results of a phase II multicenter trial of weekly docetaxel and gemcitabine as first-line therapy for patients with advanced non-small cell lung cancer.

PURPOSE: Standard treatment for advanced non-small cell lung cancer (NSCLC) consists of platinum based combination chemotherapy but efficacy is limited and treatment can be toxic. This trial evaluated a weekly regimen of docetaxel and gemcitabine for advanced NSCLC. The primary endpoint was objective response rate. Other endpoints were 1-year survival, median survival, median duration of response, median disease-free progression, safety, and quality of life. PATIENTS AND METHODS: Fifty patients with advanced NSCLC were treated. Patients received docetaxel (1 per week, 36 mg/m(2)) weeks 1-6 and gemcitabine (1 per week, 900 mg/m(2)) weeks 1, 2, 4, and 5. Each 8-week cycle was repeated for a total of three cycles. Patients completed quality of life surveys (FACT-L) before each cycle. RESULTS: The median age was 68.5 years; 74% were >60 years old. In the intent-to-treat (ITT) analysis of response, 10 patients had a partial response (20%) and five patients had stable disease (10%). The 1-year survival was 32%; median survival for all patients was 6.9 months (range, <1-26.2) and the median progression-free survival was 5.1 months (range, <1-25.5). Toxicities (> grade 3) included neutropenia, thrombocytopenia, GI disorders (nausea, vomiting, dehydration, diarrhea, stomach pain), and asthenia; 10 patients experienced hematological toxicities that were > grade 3. Quality of life decreased during the study. CONCLUSIONS: This study demonstrated that the nonplatinum doublet (docetaxel + gemcitabine) given on a weekly schedule for advanced NSCLC had efficacy similar to that reported with other regimens and was well tolerated. Therefore, this non-platinum based regimen appears promising and warrants further evaluation.

Efficacy and safety of paclitaxel poliglumex as first-line chemotherapy in patients at high risk with advanced-stage non-small-cell lung cancer: results of a phase II study.

BACKGROUND: The objectives of this open-labeled, multicenter, phase II trial were to evaluate response, survival, and tolerability in patients at high risk (Eastern Cooperative Oncology Group performance status [PS] of 2 or age >or= 70 years) with advanced-stage non-small-cell lung cancer (NSCLC) receiving single-agent paclitaxel poliglumex as first-line monotherapy. PATIENTS AND METHODS: Paclitaxel poliglumex was administered as a 10-20-minute infusion on day 1 of each 3-week cycle. Thirty patients were enrolled: 28 received paclitaxel poliglumex 175 mg/m2, and 2 received 235 mg/m2. Patients exhibiting a partial response (PR; by Response Evaluation Criteria in Solid Tumors) or stable disease (SD) continued uninterrupted treatment with paclitaxel poliglumex for or= 70 years was 7.8 months. No grade 4 nonhematologic toxicities were reported. Three patients experienced grade 3 neuropathy. Weekly hematologic assessments showed grade 3 anemia in 2 patients, grade 3 neutropenia (not associated with neutropenic fever) in 3 patients, and grade 4 neutropenia in 2 patients. No patient required growth factor support. CONCLUSION: The results of this study indicate that paclitaxel poliglumex is generally well tolerated and has activity at a dose level of 175 mg/m2 as first-line monotherapy in patients at high risk with advanced NSCLC.

Results of a phase II trial of gemcitabine in patients with non-small-cell lung cancer and a performance status of 2.

This trial was designed to determine the 1-year survival rate, efficacy, progression-free survival (PFS), and toxicity with gemcitabine in patients with stage IIIB (with pleural effusion) or stage IV non-small-cell lung cancer (NSCLC) with Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2. Gemcitabine 1250 mg/m2 was administered intravenously on days 1 and 8 of each 21-day cycle. Treatment consisted of 6 cycles; patients who responded with complete response or partial response received < or = 2 additional cycles. Forty-two patients were enrolled at 31 community-based centers between March and November 2002. Most patients had stage IV disease (74%). The median age was 73 years (range, 58-84 years), and 19% had received prior palliative radiation therapy. Patients received a median of 3 cycles (range, 1-8 cycles). The median survival was 4.8 months (range, < 1 to 19.2 months), and the estimated 1-year survival was 20%. Median PFS was 2.5 months (range, < 1 to 19.2 months), and PFS at 1 year was 11.1%. Thirty-one patients died of disease progression, and 1 each died of myocardial infarction, brain herniation, pneumonia, and respiratory failure. Seven patients were not evaluable for response; 4 refused or received no treatment, treatment in 2 failed (myocardial infarction and pneumonia), and 1 was lost to follow-up. Among 35 evaluable patients, there were 5 partial responses (14%), 10 with stable disease (29%), and 20 with disease progression (57%). Drug-related grade > or = 3 toxicities included neutropenia (18%), anemia (8%), and dyspnea (2.6%). These results suggest that patients with NSCLC with an ECOG PS of 2 may benefit from single-agent chemotherapy gemcitabine. General toxicity, including myelotoxicity, was relatively low. Further studies comparing single-agent chemotherapy with combination chemotherapy for patients with a PS of 2 are warranted.