Use Of First-line Chemotherapy Research Articles

Systemic therapy of gallbladder cancer: review of first line, maintenance, neoadjuvant and second line therapy specific to gallbladder cancer.

Gallbladder cancer is the most common malignant cancer of the biliary tract and is distinct from other forms of biliary tract cancer in several of its risk factors and molecular aberrations. Locally advanced, unresectable and metastatic gallbladder cancer is associated with a poor prognosis and systemic chemotherapy is the main form of treatment available to these patients. This review is focused on the available evidence supporting the use of first-line chemotherapy specifically for gallbladder cancer. Numerous non-randomised studies have been published and certain forms of monotherapy and combination therapy can both lead to response rates (RRs) of approximately 40% and may prove to affect overall survival, most notably a recent phase II study of triplet therapy with gemcitabine, cisplatin and nab-paclitaxel. There are however relatively few randomised phases II and III studies on which to base recommendations, but they do demonstrate significant survival advantages of gemcitabine-containing combination therapies over best supportive care and chemotherapeutic monotherapy. The ABC-02 trial established the combination of gemcitabine and cisplatin as standard therapy in 2010, but more recent phase III studies reported as conference papers may support alternative, gemcitabine-containing doublet chemotherapy regimens such as gemcitabine in combination with oxaliplatin or S1. This manuscript also highlights the available data from studies examining maintenance chemotherapy, biomarkers, neoadjuvant therapy and second line studies in gallbladder cancer; unfortunately, there is insufficient evidence to make recommendations in these regards. The prognosis for unresectable and metastatic gallbladder cancer remains poor, and biomarkers for stratifying patients to particular first line therapies are not defined. This might be improved by gallbladder cancer specific analysis and reporting, and making histological primary specific data available publicly for further analysis.

PD-015 - Optimizing the use of first-line chemotherapy in metastatic colorectal cancer patients with mucinous histology. A multicenter, retrospective, combined analysis on 897 patients

PD-015 - Optimizing the use of first-line chemotherapy in metastatic colorectal cancer patients with mucinous histology. A multicenter, retrospective, combined analysis on 897 patients

Impact of contemporary patterns of chemotherapy utilization on survival in patients with advanced cancer of the urinary tract: a Retrospective International Study of Invasive/Advanced Cancer of the Urothelium (RISC)

Cisplatin-based combination chemotherapy is the standard treatment of advanced urinary tract cancer (aUTC), but 50% of patients are ineligible for cisplatin according to recently published criteria. We used a multinational database to study patterns of chemotherapy utilization in patients with aUTC and determine their impact on survival. This was a retrospective study of patients with: UTC (bladder, renal pelvis, ureter or urethra); advanced disease (stages T4b and/or N+ and/or M+); urothelial, squamous or adenocarcinoma histology. Primary objective was overall survival (OS). Eligibility-for-cisplatin was defined by Eastern Cooperative Oncology Group performance status ≤ 1, creatinine clearance ≥ 60 ml/min, no hearing loss, no neuropathy and no heart failure. Cox regression multivariate analyses were used to establish independent associations of cisplatin versus noncisplatin-based chemotherapy on OS. 1794 patients treated between 2000 and 2013 at 29 centers were analyzed. Median follow-up was 29.1 months. About 1333 patients (74%) received first-line chemotherapy: the use of first-line chemotherapy was associated with longer OS: [hazard ratio (HR): 1.91, 95% confidence interval (CI): 1.67-2.20]. Type of first-line chemotherapy received was: cisplatin-based 669 (50%), carboplatin-based 399 (30%) and other 265 (20%). Cisplatin use was an independent favorable prognostic factor (HR: 1.54, 95% CI: 1.35-1.77). This benefit was independent of baseline characteristics or comorbidities but was associated with eligibility-for-cisplatin: eligible patients treated with cisplatin lived longer than those who were not (HR: 1.74, 95% CI: 1.36-2.21), while such benefit was not observed among ineligible patients. About 26% of patients who did not receive cisplatin were eligible for this agent. Median OS of ineligible patients was poor irrespective of the chemotherapy used. The importance of applying published criteria of eligibility-for-cisplatin was confirmed in a multinational, real-world setting in aUTC. The reasons for deviations from these criteria set targets to improve adherence. Effective therapies for cisplatin-ineligible patients are needed.

Real-world use of first-line chemotherapy in post-menopausal patients with HR-positive HER2-negative metastatic breast cancer (mBC) in a US community oncology network.

561Background: Endocrine therapy (ET) is recommended as 1st line of therapy (LOT) for patients (pts) with HR+/HER2- mBC. Chemotherapy (CT), however, has also been used, though wide practice variati...

Clinical and economic outcomes by first-line treatment among women with HR+/HER2– metastatic breast cancer in a large US health plan database

Background: Guidelines recommend that women with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (mBC) initiate hormonal therapy before chemotherapy. This study compared outcomes of women with mBC who received chemotherapy first vs hormonal therapy.Methods: A retrospective cohort study of women with mBC was conducted using a large US commercial health plan database between January 1, 2008–April 30, 2013. Subjects had evidence of a HR+/HER2– tumor sub-type in a cancer registry and use of chemotherapy or hormonal therapy in claims. Subjects were continuously enrolled for ≥6 months after metastasis and assigned to cohorts for receiving chemotherapy only or hormonal therapy only during first-line (CT-1L vs HT-1L). Adjusted incidence rates of clinically significant events were compared using a negative binomial model, and adjusted healthcare costs were compared using a generalized linear model.Results: Three hundred and twenty-four women with HR+/HER2– mBC met the selection criteria; 179 (55%) received CT-1L and 145 (45%) received HT-1L. Mortality rates did not differ between cohorts (unadjusted incidence rate ratio (IRR) = 1.67, 95% CI = 0.82–3.46; adjusted IRR = 0.64, 95% CI = 0.32–1.27). Adjusted average total all-cause healthcare costs were $11 090 for women with CT-1L and $6743 for women with HT-1L (cost ratio =1.64, 95% CI =1.36–1.99).Conclusions: Observed use of first-line chemotherapy (>50%) was higher than expected given the HR + molecular profile of the tumors. Chemotherapy use during first-line did not appear to be associated with a survival benefit, but was associated with significantly higher costs compared with the use of hormonal therapy during first-line; however, this comparison is limited by demographic and baseline characteristic differences between the two cohorts. This study contributes to understanding real-world treatment patterns and the associated clinical and economic outcomes of using chemotherapy vs hormonal therapy as a first-line treatment option for the HR+/HER2– mBC population.

Use of first-line chemotherapy for advanced pancreatic cancer: FOLFIRINOX versus gemcitabine-based therapy.

4132 Background: Pancreatic cancer (PC) is the fourth leading cause of death in the United States. It is estimated that 46,420 patients will be diagnosed in 2014 and 35,590 will die (Siegel, CA Can...

Second-line chemotherapy for advanced bladder cancer: A survey of current UK practice

Objectives•To understand current practice of the treatment of advanced bladder cancer in the United Kingdom, and in particular, the use of second-line chemotherapy.•To gain insight into uro-oncologists' use of first-line chemotherapy, imaging following first-line chemotherapy, use of second-line chemotherapy, and the role of the multidisciplinary tumor board (MTB) in making decisions about second-line chemotherapy. Materials and methods•From August 2011 to September 2011 uro-oncologists from UK cancer centers were surveyed regarding treatment of advanced bladder cancer.•Delegates at the British Uro-oncology Group conference were invited to fill out an electronic survey Results•Uro-oncologists from 28 of 42 UK cancer centers (67%) participated, who treated, on average 45 patients per year with advanced bladder cancer.•Fifteen “always” reimage after first-line chemotherapy, mostly “after 2–4 cycles.” Symptomatic patients with progressive distant disease on imaging were most likely to trigger second-line chemotherapy (P = 0.004).•Twenty-one respondents would interrupt first-line chemotherapy to start second-line chemotherapy for progressive disease and 10 would never do this. Of the patients given first-line chemotherapy, 19% go on to receive second-line chemotherapy.•Seven different regimes were specified for second-line chemotherapy with no clear preference. National Institute for Health and Clinical Excellence approval, trial data, inclusion in hospital formulary, clinical trials, or commissioning guidelines, and easy access to imaging help to access second-line chemotherapy (P≤0.001). Constraints to second-line chemotherapy were lack of evidence and patient comorbidities.•MTB effectiveness did not improve access to second-line chemotherapy. Of the 33 respondents, 19 do not rediscuss patients at the MTB before starting second-line chemotherapy. Conclusion•The investigation and treatment of patients with advanced bladder cancer following first-line chemotherapy is variable.•Optimizing the modality and frequency of imaging and increasing the usefulness of the MTB process may improve care.

Updated use of first-line chemotherapy for advanced pancreatic cancer: FOLFIRINOX versus gemcitabine.

6607 Background: Pancreatic cancer (PC) is the fourth leading cause of death in the United States. It is estimated that 45,220 patients will be diagnosed in 2013 and 38,460 will die (Siegel, CA Cancer J Clin 2013). Gemcitabine has long been the standard of care chemotherapy. Recent advances in treatment created a combination regimen (oxaliplatin, irinotecan, leucovorin, fluorouracil [FOLFIRINOX]) for patients with good Karnofsky performance status (PS) (Conroy, NEJM 2011). This retrospective analysis was conducted as an update to results reported at ASCO 2012 (Ginsburg Arlen, JCO 2012) to evaluate characteristics and overall survival (OS) of patients receiving FOLFIRINOX and gemcitabine-based treatments in a large outpatient community setting. This is the largest study describing FOLFIRINOX patients to date. Methods: Patients with advanced PC treated within The US Oncology Network entered into the iKnowMed (iKM) database between June 2010 and November 2012 were included. Patterns of treatment were characterized by the median age at diagnosis, sex, PS, and first-line metastatic chemotherapy prescribed. The primary endpoints of the analysis were OS and uptake of FOLFIRINOX within the network. Results: Compared to ASCO 2012 results, 1,000 additional patients were identified in iKM. Of the 1,714 total patients, 24% received FOLFIRINOX (up from 13% in 2012) and 76% gemcitabine-based therapy (87% in 2012). Increased utilization of FOLFIRINOX for patients with good PS began in June 2010. For all patients (55% male), the median age at diagnosis was 67 years and the majority (85%) had a PS of 70% or greater. The OS was significantly longer for FOLFIRINOX (9.6 mos) versus gemcitabine (6.3 mos) (p<0.0001). This held true for PS of 70% or greater patient given FOLFIRINOX (9.6 mos) versus gemcitabine (7 mos) (p<0.0001). Conclusions: Utilization of FOLFIRINOX has continued to expand after the publication of phase III trials. Our data in a community setting supports a survival advantage for FOLFIRINOX. Although the magnitude of benefit may be smaller in the community, we agree that FOLFIRINOX should become a standard of care for good PS patients.

Metastatic esophagogastric adenocarcinoma: trends in first-line treatment and predictive factors for the implementation of HER2 testing in clinical practice during the first year after trastuzumab market approval

Little is known about the use of first-line chemotherapy in clinical practice in patients with advanced esophagogastric adenocarcinoma, and no data have been published regarding potential obstacles for the implementation of molecular testing for targeted agents in this patient group. Here, we sought to evaluate factors influencing treatment decisions with special focus on the implementation of HER2 testing during the first year after trastuzumab market approval in Germany. A total of 754 patients undergoing treatment decisions for palliative first-line therapy in 2010 were documented using Therapiemonitor(®). Drug use and intensity of first-line treatment were analyzed. Data on HER2 testing and test algorithm are described, and variables influencing HER2 testing were selected using bivariate analysis. Significant factors were included in a multivariate logistic regression analysis. Compared with previous years, treatment intensity has further increased. The use of chemotherapy triplets rose from 10.1 % in 2006 to 60.3 % in 2010. In 2010, 49.1 % of patients were tested for HER2 and in 52.2 % of these patients the currently proposed test algorithm was used. Using multivariate logistic regression analysis age ≥67 years and "initiating institution: practice" were found to negatively impact the likelihood of HER2 testing, while treatment goal "prevention of progression", multiple metastases and a Karnofsky status >80 % showed positive correlation with HER2 testing. The tendency to use more intensive first-line chemotherapy regimens in patients with advanced esophagogastric adenocarcinoma continued in 2010. Only a minority of patients had an access to the appropriate molecular diagnostics and therefore to treatment with trastuzumab. The access was limited due to the preselection following individual, clinical and institutional factors.

Patterns and predictors of first-line chemotherapy use among adults with advanced non-small cell lung cancer in the cancer research network

BackgroundRelatively low rates of chemotherapy receipt have been observed in older patients diagnosed with advanced non-small cell lung cancer (NSCLC) in SEER-Medicare-based studies. However, little is known about variation in first-line NSCLC chemotherapy use in younger patients, health maintenance organization (HMO)-based settings, and for high-cost, novel agents, such as bevacizumab and erlotinib. MethodsA cohort of 6614 stage IIIB/IV NSCLC patients aged ≥21 years diagnosed between 2000 and 2007 was identified at four HMOs that participate in the Cancer Research Network (CRN). Demographic, comorbidity, tumor characteristics, and chemotherapy treatment data were included in logistic regression models to identify factors associated with chemotherapy receipt and tests of association examined secular and age-specific variation in first-line chemotherapy regimens. ResultsWithin 120 days of diagnosis, 3612 (55%) patients received chemotherapy; increasing from 52% of patients diagnosed in 2000 to 59% in 2007 (p<0.001). Receipt was significantly higher for patients aged <65 years (64% versus 46% in ≥65) and was inversely related to stage and comorbidites (all p<0.001). Carboplatin and paclitaxel were received most frequently. Erlotinib and bevacizumab use in the later years of the study was associated with a significant change in distributions of first-line chemotherapies (p<0.001). ConclusionsFor patients alive 30 days post diagnosis, chemotherapy use was higher in the aged population (>65 years) than previously published estimates, and higher still among younger patients. Chemotherapy use increased over the observation period, and the mix of first-line therapies used changed substantially over time. Of note, novel, high cost treatments were used in first-line therapy prior to FDA approval, increasing significantly throughout the study period. These findings demonstrate the utility of HMO CRN data to augment SEER-Medicare to conduct comparative effectiveness research related to chemotherapy use and the use of specific agents, especially among younger patients.

Sociodemographic and patient disparities in use of first-line chemotherapy (CT) in older adult patients (pts) with advanced non-small cell lung cancer (AdvNSCLC): Analysis of Surveillance, Epidemiology, and End Results (SEER)-Medicare data.

6131 Background: Clinical trials have demonstrated that CT improves survival and quality of life in pts with AdvNSCLC. Our prior studies suggest that only 26% of older pts diagnosed with AdvNSCLC received CT through 2002. In this study, we examined more recent patterns, and the effect of socio-demographics, race, and age on receipt of CT in older pts with AdvNSCLC. Methods: Medicare pts diagnosed with AdvNSCLC from 2001-2005 were identified in SEER registries. Medicare enrollment data provided demographic information (age, race, sex, marital status), augmented with census tract level data on median household income. Comorbid conditions at baseline were identified by ICD9-CM diagnoses on claims. Receipt of 1st line CT was identified based on agent-specific procedure codes in claims. Logistic regression examined predictors of 1st line CT. Results: Of 31,341 pts with Adv NSCLC, 34% received 1st line CT. As reflected in the table, poor predicted PS (PredPS), multiple medical comorbidities, and black race were associated with lower likelihood of CT receipt. Being female, married, having higher income, and being diagnosed at a later year were associated with a higher likelihood of receiving CT. Conclusions: Even when controlling for factors such as PS, our results suggest the presence of age, race, and socio-economic disparities in the receipt of 1st line CT for older patients with AdvNSCLC. [Table: see text]

Use of first-line chemotherapy for advanced pancreatic cancer: FOLFIRINOX versus gemcitabine.

e16536 Background: Pancreatic cancer (PC) is the fourth leading cause of death in the United States. It is estimated that 43,920 patients will be diagnosed in 2012 and 37,390 will die (Siegel, CA Cancer J Clin, 2012). Gemcitabine has long been the standard of care chemotherapy. Recent advances in treatment options have led to the utilization of a combination regimen (oxaliplatin, irinotecan, leucovorin, fluorouracil [FOLFIRINOX]) in patients with good Karnofsky performance status (PS). This regimen was compared to single-agent gemcitabine, presented at ASCO 2010 and recently published (Conroy, NEJM, 2011). This retrospective analysis was conducted to evaluate characteristics and overall survival (OS) of patients receiving FOLFIRINOX and gemcitabine-based treatments in a large outpatient community setting. Methods: Patients with advanced PC treated within The US Oncology Network and entered into the iKnowMed (iKM) database between June 2010 and November 2011 were included. Patterns of treatment were characterized by the median age at diagnosis, sex, PS, and first-line metastatic chemotherapy prescribed. The primary endpoints of the analysis were OS and uptake of FOLFIRINOX within the network. Results: Of the 717 patients identified within the iKM database, 13% received FOLFIRINOX and 87% gemcitabine-based therapy. Increased utilization of FOLFIRINOX for patients with good PS began in June 2010. For all patients (54% male), the median age at diagnosis was 67 years and the majority of patients (89%) had a PS of 70% or greater. The OS was significantly longer for FOLFIRINOX (8.4 months) versus gemcitabine (6.4 months) (p=0.036). OS was also significantly longer for PS of 70% or greater given FOLFIRINOX (9.0 months) versus gemcitabine (6.7 months) (p=0.022). After controlling for PS, the use of gemcitabine led to a shorter OS (HR 1.4; 95% CI: 1.02-2.01). Conclusions: Utilization of FOLFIRINOX has rapidly been adopted in patients with good PS after the publication of phase III trials. Our data in a community setting supports a survival advantage for FOLFIRINOX. Although the magnitude of benefit may be smaller in the community setting, we agree that should FOLFIRINOX become a standard of care for good PS patients.

Étude post-autorisation de mise sur le marché sur le topotécan dans le cancer bronchique à petites cellules. Utilisation du topotécan dans un service de pneumologie universitaire

Lung cancer is the leading cause of cancer related death in France and Europe. Small-cell lung carcinoma (SCLC) represents 15-20% of cases. International standards of care recommend the use of first-line chemotherapy, which has a high response rate. However, tumour recurrence occurs after a variable disease-free period. If the first-line treatment cannot be repeated during the relapse, intravenous topotecan may be used according to its market authorization (MA). We report the first French postmarketing surveillance study on the use of topotecan in the SCLC. Between August 2005 to December 2009, 26 SCLC patients received at least one cycle of intravenous topotecan in our department. All patients were treated in accordance with MA. Seventeen patients received this treatment as second line, as in the MA study, while nine patients where treated beyond the second line. In the first group, we showed that the anti-tumour efficiency of topotecan is similar to that observed in the MA study (24% response) while grade 3 to 4 haematological toxicities were less frequent. In the second group of patients, who could not have been included in the MA study, the tumour response rate was equal to 11% without an increase in severe toxicity compared to the first group. Specific or overall survival was not different between the two groups. Our study provides original public health data on the target population, the anti-tumor efficiency and the toxicity of topotecan in the treatment of SCLC.

A mathematical model of diffuse low-grade gliomas treated with PCV chemotherapy.

2065 Background: Several questions remain unanswered regarding the optimal use of first-line chemotherapy in low-grade gliomas (LGGs). Dynamic studies assessing the impact of first-line chemotherapy have shown that after the termination of chemotherapy, LGGs frequently continue to decrease in volume despite chemotherapy no longer being administered. Understanding this phenomenon is likely to be crucial to optimize chemotherapy for LGGs. The aim of the present study was to develop a mathematical model that could accurately describe the evolution of LGGs growth dynamics during and after first-line PCV chemotherapy. Methods: The model was formulated as systems of ordinary differential equations distinguishing between two cell populations: a proliferative treatment-sensitive cell population and a quiescent treatment-resistant cell population that spontaneously undergoes apoptosis. Model evaluation was performed in a series of 21 patients treated with first-line PCV chemotherapy. Results: Consistent with the biology of LGGs, the model estimated that LGGs consist largely of quiescent cells. Despite large inter-individual variability, the model correctly predicted individual tumor response profiles in the 21 patients. In analyzing evolution over time of proliferative and quiescent cell compartments, the model suggested that in some patients the six-week interval between PCV cycles might be suboptimal and that lengthening the time interval between cycles might improve the duration of response. Conclusions: We propose a mixed-effects model that accurately describes the evolution of LGGs during and after PCV chemotherapy. This model suggests that tailoring the time interval between PCV cycles according to the individual growth characteristics of LGGs may be a possible means by which to increase the efficacy of PCV chemotherapy.

Population-Based Patterns of Care in the First-Line Treatment of Patients with Advanced Esophagogastric Adenocarcinoma in Germany

Background: Randomized studies proved the efficacy of new drugs for the systemic treatment of advanced gastric cancer in the past 5 years. However, little is known about the use of firstline chemotherapy in clinical practice in patients with advanced or metastatic adenocarcinoma of the esophagogastric junction (AEG) and the stomach. We investigated temporal trends in therapy and factors influencing treatment decisions for these patients during a 4-year period. Patients and Methods: 1058 patients (median age 67 years) with advanced AEG or gastric cancers undergoing treatment decisions were documented with the Therapiemonitor® in 2006–2009. Therapiemonitor collects population-based data regarding treatment decisions and strategies. Time trends of drug use and intensity in the first-line treatment were analyzed in the entire patient group and according to age (cut-off 65 years) and Karnofsky performance status (KPS; cut-off 80%). Results: Over time, the use of oxaliplatin and docetaxel as well as capecitabine increased while cisplatin and irinotecan use slightly declined. The use of chemotherapy triplets rose from 10.1% in 2006 to 47.0% in 2009. Treatment patterns significantly varied by age and KPS: Older patients were significantly less likely to receive chemotherapy triplets, cisplatin and docetaxel but tended to more often receive oxaliplatin. Likewise, triplets, cisplatin and docetaxel were less frequently used in patients with KPS < 80%, while capecitabine and irinotecan were significantly more often used in this patient group. Conclusions: A clear tendency towards the use of more intensive chemotherapy regimens in patients with AEG and gastric cancer was observed over time. Older or less fit patients were treated preferably with monotherapy or chemotherapy doublets during 2006–2009. Oxaliplatin and docetaxel use has substantially risen.

Initial use of newer agents for advanced non-small cell lung cancer: Evidence from the National Cancer Institute Patterns of Care study.

6043 Background: Previous studies have reported on the patterns of use of first-line chemotherapy with platinum doublets in advanced NSCLC. There are no studies of patterns of use of newer agents i...

Primary Tumor Resection in Patients Presenting With Metastatic Colorectal Cancer

We conducted a Canadian population-based study to assess surgical practice patterns and outcomes among patients with metastatic colorectal cancer (mCRC) at diagnosis. We reviewed a provincial cancer registry for 2 years. Four hundred eleven patients presenting with mCRC were stratified by primary tumor resection status. Baseline characteristics, treatment modalities, and outcomes were assessed. Seventy percent of patients underwent resection. Resected patients were less likely to have rectal primaries (16% vs. 42%, P < or = 0.001) and had more obstructive symptoms (47% vs. 31%, P < or = 0.001) or bleeding (26% vs. 6%, P < or = 0.001). They experienced fewer tumor-related complications (4% vs. 22%, P < or = 0.001). Use of first-line chemotherapy was similar (61% vs. 58%, P = 0.54), but the resection cohort was more likely to receive doublet chemotherapy (57% vs. 36%, P < or = 0.01) and metastatectomy (10% vs. 0%, P < or = 0.0001). Among patients with rectal tumors, radiation use was comparable (63% vs. 58%, P = 0.68). Median survival was longer in the resection group (14 vs. 6 months, P < or = 0.001). Most patients presenting with mCRC underwent primary resection. Colonic tumors, obstruction, and bleeding were associated with resection. In situ primaries conferred more complications, despite similar use of radiation in cases of rectal cancer. Unresected patients were less likely to receive doublet chemotherapy or metastatectomy, and had inferior survival.

Trends and predictors of first-line chemotherapy use among elderly patients with advanced non-small cell lung cancer in the United States

PurposeThis study assessed first-line chemotherapy treatment patterns over time and identified predictors of chemotherapy use and treatment selection among elderly patients with newly diagnosed Stage IIIB/IV non-small cell lung cancer (NSCLC) in the United States. MethodsPatients aged 65 years and older newly diagnosed with Stage IIIB/IV NSCLC between 1997 and 2002 were identified and followed through 2003 using the Surveillance, Epidemiology and End Results (SEER)-Medicare database to evaluate temporal trends in chemotherapy treatment. Multivariate logistic regression models were estimated to identify predictors of chemotherapy treatment and factors associated with use of cisplatin/carboplatin (platinum) and either a taxane or gemcitabine versus other treatments. ResultsChemotherapy use increased from approximately 28% of Stage IIIB/IV NSCLC patients diagnosed in 1997 to 36% of patients diagnosed in 2002. Doublet therapy was most commonly used as first-line therapy, received by 74% of chemotherapy-treated patients across all study years. Use of doublet therapy with platinum and either a taxane or gemcitabine also increased over time (with the largest increase for gemcitabine combinations from 0.3% in 1997 to 11.8% in 2002). Males were more likely than females to be treated with chemotherapy (odds ratios [95% CI]: 1.14 [1.06–1.22]), as were patients in the Northeast and South relative to patients in the West (1.24 [1.13–1.36] and 1.33 [1.20–1.47], respectively). ConclusionUse of first-line chemotherapy treatment among elderly Stage IIIB/IV NSCLC patients is low, but appears to be increasing, with potential regional and gender differences in treatment. These findings are likely to be of interest to clinicians and policymakers.

Second-Line Chemotherapy With Irinotecan Plus Carmustine in Glioblastoma Recurrent or Progressive After First-Line Temozolomide Chemotherapy: A Phase II Study of the Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO)

Glioblastoma multiforme (GBM), the most frequent brain tumor in adults, is not considered chemosensitive. Nevertheless, there is widespread use of first-line chemotherapy, often with temozolomide, as a therapeutic option in patients with progressive disease after surgery and radiotherapy. However, at the time of second recurrence and/or progression, active and noncross-resistant chemotherapy regimens are required. The aim of the present multicenter phase II trial, therefore, was to ascertain the efficacy of second-line carmustine (BCNU) and irinotecan chemotherapy. Patients with histologically confirmed GBM, recurring or progressing after surgery, standard radiotherapy and a first-line temozolomide-based chemotherapy, were considered eligible. The primary end-point was progression-free survival at 6 months (PFS-6), and secondary end-points included response rate, toxicity, and survival. All patients were on enzyme-inducing antiepileptic prophylaxis. Chemotherapy consisted of BCNU (100 mg/m2 on day 1) plus irinotecan (175 mg/m2/weekly for 4 weeks), every 6 weeks, for a maximum of eight cycles. In the absence of grade 2 toxicity, the irinotecan dose was increased to 200 mg/m2. A total of 42 patients (median age, 53.4 years; median Karnofsky performance status, 80; range, 60 to 90) were included in the study. PFS-6 was 30.3% (95% CI, 18.5% to 49.7%). Median time to progression was 17 weeks (95% CI, 11.9 to 23.9). Nine partial responses (21.4%; 95% CI, 9% to 34%) were obtained. Toxicity was manageable. The BCNU plus irinotecan regimen seems active and non-cross-resistant in patients with GBM with recurrence after temozolomide-based chemotherapy.

Second-line chemotherapy in relapsing or refractory non-small-cell lung cancer: a review.

Since the increased use of first-line chemotherapy for non-small-cell lung cancer (NSCLC), second-line chemotherapy may nowadays be considered for a growing group of patients. Guidelines for second-line treatment have to be developed yet. We reviewed the published literature on second-line chemotherapy for NSCLC with emphasis on the role of factors such as pretreatment, response to first-line treatment, and length of disease-free-interval. Thirty-four single-agent-studies and 24 multidrug-studies on second-line treatment were identified. Docetaxel has been studied most extensively and is the only agent that has been studied in randomized phase III trials. Different definitions of sensitivity applied by different authors and conflicting results have been reported about the influence of response to prior chemotherapy. Since most patients are treated with a platinum-based regimen in the first line, platinum resistance usually is a major consideration for the use of second-line agents. We argue, however, that a more general definition of drug resistance is more appropriate than resistance to platinum only. Criteria to select NSCLC patients for second-line treatment have not been defined yet. This is also important in light of the upcoming necessity to test new drugs in pretreated instead of treated patients. Guidelines for second-line treatment of NSCLC based on clinical information on drug sensitivity to first-line therapy need to be developed.