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.

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.

Improving incidence of code status documentation through process and discipline.

Documentation of a patient's preferred code status is a critical outcome of advance care planning. Although there is agreement that code status is valuable information, little progress has been made to increase the incidence of documented code status within the medical record in an outpatient setting. Incidence of code status documentation in the community oncology setting has not been studied. In April 2013, the US Oncology Network and McKesson Specialty Health launched a new advance care planning initiative for the purpose of promoting conversations between clinicians and patients regarding end-of-life care preferences. The program-My Choices, My Wishes-provides a systematic approach for learning about and documenting a patient's values and goals for care in the electronic health record. Code status documentation is one of several program performance measures. During the 14-month period from August 1, 2013, through September 30, 2014, collective sites participating in My Choices, My Wishes included discrete code status documentation within the medical record for 5,467 patients with metastatic disease. Although much work remains, early results show promise for improvement in incidence of code status documentation within health records in the outpatient setting.

Randomized phase II trial of erlotinib with and without entinostat in patients with advanced non-small-cell lung cancer who progressed on prior chemotherapy.

PURPOSE: Histone deacetylase inhibitors (HDACis) have been shown to overcome resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) linked to epigenetic changes and epithelial-mesenchymal transition (EMT) state. This randomized phase II study evaluated the outcome of erlotinib with and without the isoform selective HDACi, entinostat. PATIENTS AND METHODS: Previously treated patients with stage IIIB/IV non-small-cell lung cancer, no prior EGFR-TKIs, and performance status ≤ 2 were randomly administered erlotinib 150 mg on days 1 through 28 plus entinostat 10 mg orally on days 1 and 15 every 28 days (EE) or erlotinib plus placebo (EP). The primary end point was 4-month progression-free survival (PFS) rate with additional end points including 6-month PFS rate, PFS, and overall survival (OS). Exploratory analyses included EMT- and EGFR-related biomarker analysis on archival tissue. RESULTS: One hundred thirty-two patients were enrolled (EE, 67; EP, 65). The 4-month PFS rate was comparable for both groups (EE, 18% v EP, 20%; P = .7). In the subset of patients with high E-cadherin levels, OS was longer in the EE group compared with the EP group (9.4 v 5.4 months; hazard ratio, 0.35; 95% CI, 0.13 to 0.92; P = .03) with a corresponding trend toward increased PFS. The adverse event (AE) profile was acceptable, with rash, fatigue, diarrhea, and nausea the most common AEs in both groups. CONCLUSION: Erlotinib combined with entinostat did not improve the outcomes of patients in the overall study population when compared with erlotinib monotherapy. High E-cadherin expression levels at time of diagnosis indicate an increased sensitivity to HDACi/EGFR-TKI inhibition providing the basis for a biomarker-driven validation study.

Creating a process to standardize regimen order sets within an electronic health record.

PURPOSE: US Oncology uses regimen order sets in clinical practice to treat patients. However, the process to assure accuracy and upkeep of these order sets has not been described. The purpose of this project was to evaluate the regimens housed in the electronic health record, iKnowMed, to determine their appropriateness and accuracy. MATERIALS AND METHODS: US Oncology conducted an audit of its standardized regimen library. A utilization review compared chemotherapy regimens in the library and consolidated order sets on the basis of past utilization. Next, internal and external clinical pharmacists were contracted to verify the accuracy, dose, duration, and cycle length of regimens. References cited in the regimen library were evaluated. New or updated references or clinical practice standards were added or modified when necessary. US Oncology corporate pharmacists reviewed the recommendations and discussed findings with an oversight committee. Final proposals were voted on before being incorporated into iKnowMed. An internal database tracking system tool for all reviewed recommendations was created to track and communicate needed changes to the electronic health record. RESULTS: Out of 511 regimen order sets, 51 were recommended for removal or consolidation. Of the remaining 460 regimen order sets, all had some administrative changes. Specifically, 75% had title changes, 14% had cycle-related changes, 31% had reference updates, and 13% had dosing updates. CONCLUSION: Electronic health records systems, such as iKnowMed, can provide standardized order sets for a large oncology network. However, the regimens need to be evaluated routinely using standardized procedures to ensure they are accurate and current.

Pathways, outcomes, and costs in colon cancer: retrospective evaluations in two distinct databases.

PURPOSE: The goal of this study was to use two separate databases to evaluate the clinical outcomes and the economic impact of adherence to Level I Pathways, an evidence-based oncology treatment program in the treatment of colon cancer. PATIENTS AND METHODS: The first study used clinical records from an electronic health record (EHR) database to evaluate survival according to pathway status in patients with colon cancer. Disease-free survival in patients receiving adjuvant treatment and overall survival in patients receiving first-line therapy for metastatic disease was calculated. The second study used claims data from a national administrative claims database to examine direct medical costs and use, including the cost of chemotherapy and of chemotherapy-related hospitalizations according to pathway status. RESULTS: Overall costs from the national claims database-including total cost per case and chemotherapy costs-were lower for patients treated according to Level I Pathways (on-Pathway) compared with patients not treated according to Level I Pathways. Use of pathways was also associated with a shorter duration of therapy and lower rate of chemotherapy-related hospital admissions. Survival for patients on-Pathway in the EHR database was comparable with those in the published literature. CONCLUSION: Results from two distinct databases suggest that treatment of patients with colon cancer on-Pathway costs less; use of these pathways demonstrates clinical outcomes consistent with published evidence.

An open-label, single-arm, phase 2 trial of panitumumab plus FOLFIRI as second-line therapy in patients with metastatic colorectal cancer.

BACKGROUND: This prospective analysis evaluated the effect of tumor KRAS status on efficacy of second-line panitumumab plus folinic acid/5-fluorouracil/irinotecan (FOLFIRI). METHODS: This phase 2, open-label, single-arm study enrolled patients with unresectable, measurable metastatic colorectal cancer (mCRC) after failure of first-line treatment with oxaliplatin-based chemotherapy plus bevacizumab. Patients received panitumumab 6 mg/kg plus FOLFIRI every 2 weeks until disease progression or intolerability. Tumor assessments per Response Evaluation Criteria in Solid Tumors (RECIST) were performed by the investigators every 8 weeks from weeks 8-32 and every 12 weeks thereafter. KRAS status was determined by real-time polymerase chain reaction (PCR) on DNA extracted from fixed tumor sections. Efficacy endpoints included objective response rate, progression-free survival (PFS), and overall survival (OS). Safety endpoints included incidence of adverse events (AEs). Endpoints were evaluated by tumor KRAS status. RESULTS: Of 116 patients enrolled, 109 patients with known tumor KRAS status received treatment; 59% had wild-type KRAS, and 41% had mutant KRAS. Fifteen patients (23%) with wild-type KRAS and 7 patients (16%) with mutant KRAS had a complete or partial response to treatment. Median PFS was 26 weeks (95% CI, 19-33 weeks) and 19 weeks (95% CI, 12-25 weeks) in the wild-type KRAS and mutant KRAS strata, respectively. Median OS was 50 weeks (95% CI, 39-76 weeks) and 31 weeks (95% CI, 23-47 weeks) in wild-type KRAS and mutant KRAS strata, respectively. Skin-related toxicities (86% of all patients) and diarrhea (74%) were the most common AEs. CONCLUSION: Panitumumab plus FOLFIRI numerically improved objective response rate, PFS, and OS in favor of patients with wild-type KRAS tumors. The safety profile was consistent with panitumumab plus FOLFIRI trials in similar patient populations.

Pathways, outcomes, and costs in colon cancer: retrospective evaluations in 2 distinct databases.

OBJECTIVE: The goal of this study was to use 2 separate databases to evaluate the clinical outcomes and the economic impact of adherence to Level I Pathways, an evidence-based oncology treatment program in the treatment of colon cancer. PATIENTS AND METHODS: The first study used clinical records from an electronic health record (EHR) database to evaluate survival according to pathway status in patients with colon cancer. Disease-free survival in patients receiving adjuvant treatment and overall survival in patients receiving first-line therapy for metastatic disease was calculated. The second study used claims data from a national administrative claims database to examine direct medical costs and use, including the cost of chemotherapy and of chemotherapy-related hospitalizations according to pathway status. RESULTS: Overall costs from the national claims database-including total cost per case and chemotherapy costs-were lower for patients treated according to Level I Pathways (on- Pathway) compared with patients not treated according to Level I Pathways. Use of pathways was also associated with a shorter duration of therapy and lower rate of chemotherapy-related hospital admissions. Survival for patients on- Pathways in the EHR database was comparable with that in the published literature. CONCLUSION: Results from 2 distinct databases suggest that treatment of patients with colon cancer on-Pathways costs less; use of these pathways demonstrates clinical outcomes consistent with published evidence.

A phase III randomized trial of gemcitabine-oxaliplatin versus carboplatin-paclitaxel as first-line therapy in patients with advanced non-small cell lung cancer.

PURPOSE: This phase III study compared the efficacy and tolerability of gemcitabine and oxaliplatin (GEMOX) with paclitaxel and carboplatin (PCb) in chemotherapy-naive patients with stage IIIB/IV non-small cell lung cancer. PATIENTS AND METHODS: Patients aged 18 years or older were randomized to PCb (paclitaxel 225 mg/m followed by carboplatin area under the curve = 6 on day 1 every 3 weeks) or GEMOX (gemcitabine 1,000 mg/m on days 1 and 8 followed by oxaliplatin 130 mg/m on day 1 every 3 weeks) for up to six cycles. The primary end point was progression-free survival (PFS), with tumor response rate, overall survival (OS), and quality of life as secondary end points. RESULTS: : The study was terminated after 383 patients had been randomized (371 received treatment) as the incidence of adverse events had exceeded the protocol-specified safety threshold (≥ 20% in either arm). No formal statistical comparisons were conducted. Median PFS was 4.44 months and 4.67 months in the GEMOX and PCb groups, respectively. Objective response rates (complete or partial) were 15.2% and 22.4% in the GEMOX and PCb arms, respectively. Median OS was 9.90 months (GEMOX) and 9.24 months (PCb); post hoc analyses showed median OS in patients aged 70 years or older to be similar to those younger than 70 years. PFS was similar in both groups of patients with adenocarcinoma histology, although OS favored the GEMOX group. Quality of life was improved from baseline in both groups. Toxicity profiles were comparable between the groups. CONCLUSION: PFS, OS, and objective response rates with GEMOX were similar to PCb. Nevertheless, toxicities limit the adoption of this regimen for routine use in advanced non-small cell lung cancer.

Benchmarks for value in cancer care: an analysis of a large commercial population.

PURPOSE: Cancer costs are increasing at an unprecedented rate. Key cost drivers include chemotherapy, hospital admissions/emergency room visits, and aggressive end-of-life care. We sought to evaluate these costs in a commercial payer population in collaboration with consultants from Milliman. PATIENTS AND METHODS: We used a retrospective analysis of Medstat 2007 to evaluate chemotherapy costs and use. Included patients had a cancer diagnosis; received chemotherapy during the evaluation period; had at least 1 day of coverage between January 1 and December 31, 2007 (medical and prescription coverage); was younger than age 70, and had active employment or was the spouse of an active employee. Costs are allowed amounts and are trended until 2009. Admission rates and emergency room visits are reported. Hospice use and chemotherapy during the last 14 and 30 days of life were also evaluated. RESULTS: In this commercial population of 14 million patients, 0.68% had claims for a cancer diagnosis; approximately 22% of those received chemotherapy during the study time period. Patients with cancer receiving chemotherapy averaged $111,000 per year in total medical and pharmacy costs. The average hospitalization rate for any reason was 1 admission/yr. Approximately 40% (or 0.4 admits/year) were identified as being chemotherapy related. Of the 3.5% of patients who died in the hospital, 51% received chemotherapy within 30 days of death. CONCLUSION: Understanding the costs of cancer care offers opportunities to formulate a strategic plan to control cancer costs and maintain quality care. Comprehensive cancer solutions to address the full spectrum of care will facilitate improved quality and patient outcomes.

Cost effectiveness of evidence-based treatment guidelines for the treatment of non-small-cell lung cancer in the community setting.

PURPOSE: The goal of this study was to evaluate the cost-effectiveness of Level I Pathways, a program designed to ensure the delivery of evidence-based care, among patients with non-small-cell lung cancer (NSCLC) treated in the outpatient community setting. PATIENTS AND METHODS: We included patients with NSCLC initiating a chemotherapy regimen between July 1, 2006, and December 31, 2007, at eight practices in the US Oncology network. Patients were characterized with respect to age, sex, stage, performance status, and line of therapy and were classified by whether they were treated according to Level I Pathways guidelines. Twelve-month cost of care and overall survival were compared between patients treated on Pathway and off Pathway. A net monetary benefit approach and corresponding cost-effectiveness acceptability curves were used to evaluate the cost-effectiveness of Level I Pathways. RESULTS: Overall, outpatient costs were 35% lower for on-Pathway versus off-Pathway patients (average 12-month cost, $18,042 v $27,737, respectively). Costs remained significantly less for patients treated on Pathway versus off Pathway in the adjuvant and first-line settings, whereas no difference in overall cost was observed in patients in the second-line setting. No difference in overall survival was observed overall or by line of therapy. In the net monetary benefit analysis, after adjusting for potential confounders, we found that treating patients on Pathway was cost effective across a plausible range of willingness-to-pay thresholds. CONCLUSIONS: Results of this study suggest that treating patients according to evidence-based guidelines is a cost-effective strategy for delivering care to those with NSCLC.

Lack of correlation between epidermal growth factor receptor status and response to Panitumumab monotherapy in metastatic colorectal cancer.

PURPOSE: Panitumumab, a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody, is approved as monotherapy for the treatment of metastatic colorectal cancer. We evaluated the association of tumor EGFR expression levels with outcomes in patients with chemorefractory metastatic colorectal cancer. EXPERIMENTAL DESIGN: Two phase II, multicenter, single-arm, open-label studies enrolled chemorefractory patients with tumors expressing low/negative (1-9%/<1%; Low/Negative EGFR study) or high (> or =10%; High EGFR study) levels of EGFR. Patients received panitumumab 6 mg/kg every two weeks until disease progression or intolerance. End points included objective response rate (per response evaluation criteria in solid tumors), progression-free survival (PFS), overall survival (OS), and safety. Exploratory analyses by tumor KRAS status were carried out. RESULTS: A total of 203 patients (Low/Negative EGFR) and 185 patients (High EGFR) enrolled in the studies. The overall response rate was 5.7% [95% confidence interval (95% CI), 2.6-10.5] in patients with low/negative EGFR and 4.2% (95% CI, 1.6-9.0) in patients with high EGFR; the response rate at week 16 was 4% in both studies (all partial responses). Median PFS times were 8.1 weeks (95% CI, 7.1-12.6), 8.1 weeks (95% CI, 7.4-11.1), and 7.3 weeks (95% CI, 7.1-7.6) in patients with negative, low, and high levels of EGFR expression, respectively. PFS and OS were longer in patients with wild-type KRAS than those with mutant KRAS. As expected, most adverse events were skin related. CONCLUSIONS: These studies confirm previous reports that tumor EGFR expression levels are not associated with efficacy with an anti-EGFR antibody and that anti-EGFR antibody therapy should be limited to those patients whose tumors express wild-type KRAS.

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.

Phase II trial of R115777 (NSC #70818) in patients with advanced colorectal cancer: a Southwest Oncology Group study.

PURPOSE: The purpose of this Phase II multi-institutional trial was to determine the efficacy and toxicity of R115777 in previously untreated patients with metastatic colorectal carcinoma. PATIENTS AND METHODS: Patients were required to have histologically confirmed colorectal cancer with distant metastatic disease that was not surgically curable. They could not have received prior chemotherapy for metastatic disease. R115777 was given at a dose of 300 mg p.o. twice a day for 21 days every 28 days until tumor progression or toxicity or other reason for discontinuation occurred. The primary endpoint was to determine the confirmed response probability with this treatment. RESULTS: There were 55 eligible patients accrued to the study. There were no complete responses, but one confirmed partial response for a confirmed response probability of 2% (95%CI 0-10%). Three additional patients had an unconfirmed partial response for an overall response probability of 7%. The time to treatment failure was 1.7 months and the estimated median survival was 8.1 months. One patient died of treatment related infection and there were 7 other patients with grade 4 toxicities consisting of neutropenia, leukopenia, febrile neutropenia and thrombocytopenia, depression, increased bilirubin, anemia, and pneumonitis/infiltrates. CONCLUSION: R115777 given as a single agent by this dose and schedule is ineffective in patients with metastatic colorectal cancer.

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.

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.

Phase II trial of paclitaxel, ifosfamide, and carboplatin in extensive-stage small cell lung cancer.

Extensive-stage small cell lung cancer (ES-SCLC) remains a therapeutic challenge to the medical oncologists. We evaluated the triplet combination of paclitaxel (175 mg/m(2) over 1 h), ifosfamide (2.5 gm/m(2) over 1 h) and carboplatin (AUC=6 over 0.5 h) (PIC) all given on day 1 of a 21 day schedule. Thirty-five patients were entered with a median age of 59 years (range 40-79). The ECOG PS was 0-1 in 86%. A median of 6 cycles were delivered (range 1-6). The principal toxicity was neutropenia with 66% of patients experiencing grade 4 neutropenia. Only 9% of patients experienced febrile neutropenia. One treatment-related death (3%) due to neutropenic sepsis occurred. Non-hematologic toxicity was minimal. The overall response rate was 71% (15% complete response, 56% partial responses). Quality of life appeared to be stable across time. The median survival time was 9.5 months (95% confidence interval (CI), 6.7-13.2 months) with a 1- and 2-year survival rates of 43% (95% CI, 26-59%) and 16% (95% CI, 2-30%). PIC has activity in ES-SCLC and is associated with a response rate and survival profile similar to other combinations in this disease setting. This regimen has a tolerable toxicity profile and a favorable and convenient administration schedule.