Cycles Of First-line Chemotherapy Research Articles

Management of Non-Small Cell Lung in Cancer Patients with Stable Disease

Disease stabilization after first-line chemotherapy, also known as induction chemotherapy, is defined, according to the Response Evaluation Criteria in Solid Tumours (RECIST), as having neither sufficient shrinkage to qualify as a partial response (PR) nor sufficient increase to qualify as progressive disease (PD). In oncology, stable disease (SD) has often been viewed as an equivocal result and is therefore of unclear clinical value. In SD patients with advanced non-small cell lung cancer (NSCLC) who have already received four cycles of first-line chemotherapy with platinum agents plus a third-generation agent (gemcitabine, vinorelbine, docetaxel or paclitaxel) or pemetrexed, the continuation of the original treatment is not recommended according to the American Society of Clinical Oncology (ASCO) guidelines. The ASCO guidelines recommend maintenance with bevacizumab or cetuximab, as tolerated until progression, only for platinum-based chemotherapy combined with bevacizumab or cetuximab. Several trials and a meta-analysis have, however, suggested a role for maintenance treatment in patients without progression after induction chemotherapy. The National Comprehensive Cancer Network guidelines recently suggested that maintenance therapy may be considered after four to six cycles of induction platinum doublets for patients with tumour responses or SD, and recommended first-line treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in EGFR mutated patients to continue until PD. More recently, two randomized clinical trials that compared pemetrexed or erlotinib with a placebo demonstrated a better overall survival in favour of maintenance therapy. In subgroup analyses for both trials, patients with SD after first-line induction chemotherapy had pronounced survival benefits when erlotinib or pemetrexed maintenance therapy was given, although this result was not achieved in patients with a complete response or PR after induction chemotherapy. The management of patients with SD after first-line chemotherapy is an important issue because only a minority of patients with advanced NSCLC experience tumour shrinkage after standard platinum-based chemotherapy. Many more patients experience either SD or PD. The notion that the prognosis of SD patients varies greatly due to the complexity of SD should, however, be taken into careful consideration for the treatment decision. Therefore, suggestions for the further classification of SD are urgently needed to enable the use of an alternative therapy at an early time.

Selection of chemotherapy for patients with advanced non–small cell lung cancer

Chemotherapy remains the first-line treatment for most patients with stage IV non-small cell lung cancer (NSCLC), but optimal regimens are now defined by histology. Platinum-based regimens with pemetrexed, bevacizumab, or both are reasonable first-line options for patients with nonsquamous NSCLC. The standard treatment for squamous NSCLC remains a platinum doublet with a drug other than pemetrexed. Maintenance therapy is emerging as a treatment strategy for patients who do not progress after four cycles of first-line chemotherapy. In the maintenance setting, pemetrexed and erlotinib significantly prolong overall survival compared with placebo after the completion of first-line chemotherapy.

A double‐blind, randomized, placebo‐controlled, phase 2 study of maintenance enzastaurin with 5‐fluorouracil/leucovorin plus bevacizumab after first‐line therapy for metastatic colorectal cancer

Enzastaurin and bevacizumab have demonstrated synergistic antitumor effects and, in phase 1 studies, the combination was well tolerated. This phase 2 study assessed enzastaurin with 5-fluorouracil/leucovorin plus bevacizumab as maintenance therapy for metastatic colorectal cancer (MCRC). Patients with locally advanced or MCRC and stable or responding disease after completing 6 cycles of first-line chemotherapy randomly received a loading dose of enzastaurin 1125 mg, followed by 500 mg/d subsequent doses or placebo. Both arms received 5-fluorouracil/leucovorin (leucovorin 400 mg/m(2) intravenously [IV], 5-fluorouracil 400-mg/m(2) bolus, 5-fluorouracil 2400 mg/m(2) IV) plus bevacizumab 5 mg/kg IV, every 2 weeks. The primary endpoint was progression-free survival (PFS), from randomization. Overall survival (OS) and PFS were also assessed from start of first-line therapy. Enrollment was stopped, and the final analysis was conducted after 73 PFS events. Fifty-eight patients were randomized to enzastaurin and 59 to placebo. For the enzastaurin and placebo arms, respectively, the median cycles received were 9 and 10, and the median PFS was 5.8 and 8.1 months (hazard ratio [HR], 1.35; 95% confidence interval [CI], 0.84-2.16; P = .896). Median OS was not calculable because of high censoring (77.6% enzastaurin; 91.5% placebo). The median PFS from start of first-line therapy was 8.9 months for enzastaurin and 11.3 months for placebo (HR, 1.39; 95% CI, 0.86-2.23; P = .913). More enzastaurin patients developed thrombosis or embolism compared with placebo (15.8% and 1.7%; P = .008). One possibly enzastaurin-related death occurred because of arrhythmia. Enzastaurin combined with bevacizumab-based therapy is tolerable, but does not improve PFS during maintenance therapy in patients with MCRC compared with bevacizumab-based therapy alone.

Interim 18f-PDGPET for Aggressive Non-Hodgking's Lymphoma: A Systematic Review and Meta-Analysis

Abstract 5183 Background:The advantage of using interim 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) scan in the clinical work-up of patients with non-Hodgkin's lymphoma (NLH) is unclear. Data from meta-analyses are inconclusive, mainly because of the low number of patients evaluated and heterogeneity among studies. New clinical investigations, focused on this topic, have been recently published. We conducted an updated systematic review on the role of 18PDG-PET for the interim evaluation in patients with aggressive lymphomas. Materials and Methods:Medline, Embase, Scopus and Databases were searched for relevant studies through March 2011. We included studies that evaluated FDG-PET performed between the first and the fourth cycle of first-line chemotherapy. Patients were selected when they were evaluated for response assessment with interim 18FDG-PET. For each study, we constructed a 2 × 2 contingency table consisting of true positive (TP), false positive (FP), false negative (FN), and true negative (TN), where all patients were categorized according to whether they were PET positive or negative, and whether they experienced treatment failure. A meta-analysis of the prognostic accuracy was performed. Results:We selected 16 out of 46 studies, involving 1256 patients with aggressive NHLs (90% with Diffuse Large B-Cell Lymphoma); 1157 patients met our inclusion criteria and were considered for the final analysis. Interim18FDG-PET, performed after a median of 3 cycles of chemotherapy (range 1–6 cycles), gave true and false negative results in 641 (56 %) and 65 (6%) patients, respectively. Therefore, 18FDG-PET had an overall sensitivity of 0.80 (95% CI, 0.69 to 0.88) and a specificity of 0.84 (95% CI, 0.76 to 0.90) (figure). Heterogeneity among studies was substantial. Conclusion:Because of data heterogeneity, interim 18FDG-PET for aggressive NHL patients remains an unproven test for routine clinical practice. Its role should be further evaluated in clinical researches with homogeneous treatments and standardized imaging. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Erlotinib as maintenance therapy in patients with advanced non-small cell lung cancer

Three randomized trials (SATURN, ATLAS and IFCT-GFPC 0502) have demonstrated that the oral antiepidermal growth factor receptor tyrosine kinase inhibitor erlotinib can improve progression-free survival (PFS) and overall survival (OS), as maintenance therapy after first-line chemotherapy in advanced non-small cell lung cancer. We pooled the results of these three trials by performing a meta-analysis of hazard ratios (HRs) and the 95% confidence intervals (CIs) for the PFS and the OS for maintenance erlotinib versus observation, standard therapy or placebo. The benefits in the predefined subgroups of patients [according to histology, sex, performance status (PS), and smoking status] were assessed. The OS was superior in the 963 patients treated with erlotinib than in the 979 nontreated patients [HR=0.87 (P=0.003), corresponding to a 13% reduction in the risk of death. The pooled HR for the PFS is 0.76 (P<0.00001), corresponding to a 24% lower risk of being progression free]. All the patients in the subgroup analysis experienced a benefit from erlotinib and, in particular, never-smoking women with nonsquamous histology with a PS of 0. Both responders and those with stable disease obtain PFS benefit. The addition of maintenance erlotinib significantly improves PFS and OS in patients with advanced non-small cell lung cancer who had not progressed after four cycles of first-line chemotherapy. The benefit does not seem to be limited to a particular subgroup, although it is more pronounced in never-smoking women patients with nonsquamous carriers with a PS of 0.

2011 Focused Update of 2009 American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non-Small-Cell Lung Cancer.

An American Society of Clinical Oncology (ASCO) focused update updates a single recommendation (or subset of recommendations) in advance of a regularly scheduled guideline update. This document updates one recommendation of the ASCO Guideline Update on Chemotherapy for Stage IV Non-Small-Cell Lung Cancer (NSCLC) regarding switch maintenance chemotherapy. Recent results from phase III clinical trials have demonstrated that in patients with stage IV NSCLC who have received four cycles of first-line chemotherapy and whose disease has not progressed, an immediate switch to alternative, single-agent chemotherapy can extend progression-free survival and, in some cases, overall survival. Because of limitations in the data, delayed treatment with a second-line agent after disease progression is also acceptable. Seven randomized controlled trials of carboxyaminoimidazole, docetaxel, erlotinib, gefitinib, gemcitabine, and pemetrexed have evaluated outcomes in patients who received an immediate, non-cross resistant alternative therapy (switch maintenance) after first-line therapy. In patients with stage IV NSCLC, first-line cytotoxic chemotherapy should be stopped at disease progression or after four cycles in patients whose disease is stable but not responding to treatment. Two-drug cytotoxic combinations should be administered for no more than six cycles. For those with stable disease or response after four cycles, immediate treatment with an alternative, single-agent chemotherapy such as pemetrexed in patients with nonsquamous histology, docetaxel in unselected patients, or erlotinib in unselected patients may be considered. Limitations of this data are such that a break from cytotoxic chemotherapy after a fixed course is also acceptable, with initiation of second-line chemotherapy at disease progression.

FDG-PET as a Potential Tool for Selecting Patients with Advanced Non–Small Cell Lung Cancer Who May Be Spared Maintenance Therapy after First-Line Chemotherapy

To investigate whether 18F-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) may be a potential tool to select a subgroup of patients who might be spared maintenance treatment, if the metabolic response after first-line chemotherapy could predict time-to-progression (TTP). A total of 43 patients who underwent baseline FDG-PET scan and did not show disease progression (DP) after 4 cycles of first-line chemotherapy were enrolled and underwent second FDG-PET 3 weeks after completion of the first-line chemotherapy. The primary endpoint was to compare percent decrease in maximum standard uptake value (SUVmax) between early (TTP after second PET examination <8 weeks) and late (TTP ≥8 weeks) DP subgroups. Secondary endpoints were to determine whether fractional decrease in SUVmax could predict TTP and overall survival (OS), both calculated from the date of the second FDG-PET. Percent decreases in SUVmax in late DP subgroup were greater than those in early DP subgroup (mean reduction, 54.7% ± 27.2% vs. 27.8% ± 46.8%, P = 0.021). Receiver operating characteristic curves identified a 50.0% decrease in SUVmax as the optimal threshold to distinguish these subgroups. Using this value as the cutoff resulted in a positive predictive value of 82.6% and negative predictive value of 60.0% in predicting TTP ≥8 weeks. Patients with SUVmax decrease <50% had significantly longer median TTP (3.0 vs. 1.5 months, P = 0.001) and OS (not reached vs. 14.2 months, P = 0.003). Fractional decrease in SUVmax of the main lesion after completion of 4 cycles of chemotherapy may discriminate patients with TTP ≥8 weeks and predict TTP and OS in patients with advanced NSCLC.

Le carcinome pléomorphe du poumon. À propos d’un cas

Pleomorphic carcinoma is a rare malignancy belonging to the family of nonsmall cell lung cancers. A 40-year-old man, a smoker, was hospitalized for thoracic pain and dry cough with a deteriorating general condition. The imaging showed a "drop ball" of both lungs. The pathological evidence was obtained by lung biopsy under scanographic control. The presence of supraclavicular and abdominal nodes classified the tumour as stage IV. The patient received six cycles of first-line chemotherapy associating cisplatin and vinorelbine. However, the disease continued to progress and distant metastases were observed. The patient died 6 months after the diagnosis. Pleomorphic carcinoma is identified by purely histological criteria: the concomitant presence of malignant epithelial and homologous sarcomatoid spindle-cell components. Like the other nonsmall cell lung cancers, the treatment is primarily surgical, and the invasive nature of this tumour makes it very difficult. Pleomorphic carcinoma has a poorer prognosis than conventional nonsmall cell lung cancers despite surgery, irradiation and chemotherapy, because relapse occurs early.

A double-blind, randomized, placebo-controlled, phase II study of maintenance enzastaurin with 5-FU/leucovorin plus bevacizumab following first-line therapy for metastatic colorectal cancer (mCRC).

3527 Background: Maintenance therapy is designed to maximize progression-free survival (PFS) and minimize toxicity in mCRC. Enzastaurin (ENZ) is an oral serine/threonine kinase inhibitor targeting PKCβ and AKT/PI3K pathways. Preclinical studies showed synergistic antitumor effects when ENZ was combined with bevacizumab (BV). In phase I studies, the combination was well tolerated. Our phase II study assessed ENZ with 5-FU/Leucovorin (5-FU/LV) plus BV as maintenance therapy for mCRC. Methods: Patients had locally advanced or mCRC, and completed 6 cycles of first-line chemotherapy ≤4 wks prior to randomization. Arm A received a loading dose of ENZ 1125 mg, then 500 mg/d subsequent doses. Arm B received placebo. Both groups received 5-FU/LV (LV 400 mg/m2 IV, 5-FU 400 mg/m2 bolus, 5-FU 2400 mg/m2 IV) plus BV 5 mg/kg IV, every 2 wks. Patients were treated with 5-FU/LV plus BV plus either ENZ or placebo until disease progression (PD) or 1 yr. Primary endpoint: PFS from randomization. Secondary endpoints were overall survival (OS) from randomization, and OS and PFS from start of first-line therapy. Analysis was done after 50 events (objective or clinical PD or death) to compare endpoints between the treatment arms. Results: 58 patients were randomized to Arm A (57 treated), 59 to Arm B (58 treated). 82 (70.1%) patients discontinued treatment (Arm A, 42 [72.4%]; Arm B, 40 [67.8%]), mostly due to PD. Median cycles were 9 in Arm A, 10 in Arm B. Median PFS (months) was 5.8 in Arm A and 8.1 in Arm B (hazard ratio [HR]=1.35, 95% CI: 0.84, 2.16; protocol specified one-sided test, p=0.896). Median OS was not calculable due to high censoring (77.6% in Arm A and 91.5% in Arm B). Median PFS (months) from start of first-line therapy was 8.9 in Arm A and 11.3 in Arm B (HR=1.39, 95% CI: 0.86, 2.23; one-sided, p=0.913). More patients developed thrombosis or embolism (TE), including pulmonary embolism, on Arm A (5 [8.8%] patients had grade 3 and 5 [8.8%] grade 4 TE); Arm B had (no grade 3 and 1 [1.7%] grade 4 TE). Conclusions: ENZ did not show an advantage in PFS compared to BV-based therapy alone. Development of maintenance therapy with ENZ is not recommended for mCRC.

NGR-hTNF in previously treated patients with malignant pleural mesothelioma (MPM) .

7089 Background: NGR-hTNF exploits the tumor-homing peptide NGR for selectively targeting tumor necrosis factor to tumor blood vessels. Methods: Here we report the long-term results of a phase II trial testing NGR-hTNF in 57 MPM patients (pts) who had failed a pemetrexed-based regimen. NGR-hTNF was given as 1-hour infusion at 0.8 µg/m2 every 3 weeks (q3w; n=43) or weekly (q1w; n=14) in a subsequent cohort. Moreover, we assessed the impact on outcome of the systemic neutrophil-to-lymphocyte ratio (NLR), an index of the host immune response to tumor. Median baseline NLR was 3 (range 1-23). Results: In the whole study population (n=57), one grade 3 drug-related toxicity was observed and common grades 1-2 were transient chills (75% of pts). There was no higher toxicity using the q1w schedule. Median progression-free survival (PFS) was 2.8 months (95% CI 2.2-3.3). The disease control rate was 46% (26/57 pts; 95% CI 33-60%) and was maintained for a median time of 4.7 months (95% CI 4.0-5.4). With a median follow up of 28.6 months, the overall survival (OS) rates at 1 and 2 years were 47% and 15%, respectively. The 6-month PFS and 2-year OS rates were 11% and 10% in q3w cohort vs 36% and 29% in q1w cohort, respectively. In pts with disease control (n=26), median PFS and 2-year OS rate were 4.4 months and 11% in q3w cohort vs 9.1 months and 57% in q1w cohort, respectively. In a landmark analysis set at 2 months (1st restaging), median OS was longer in pts who had achieved disease control compared with those who had progressed (14.7 vs 6.8 months; p=0.03). By multivariate analyses, a PS of 0 (HR=0.38; p=0.02) and a baseline NLR ≤ 3 (HR=0.40; p=0.005) were associated with longer survival, while no associations were detected between OS and age, sex, histology, EORTC score and treatment-free interval on prior therapy. Median OS were 17.4 vs 8.0 months in pts with PS 0 or PS 1-2 and 15.7 vs 5.6 months in pts with NLR ≤ or > 3, respectively. Conclusions: Based on these results, NGR-hTNF 0.8 µg/m2 q1w is currently tested in a placebo-controlled phase II trial as a maintenance treatment in MPM pts who did not progress after 6 cycles of first-line chemotherapy and in a double-blind phase III trial evaluating best investigator’s choice ± NGR-hTNF in relapsed MPM.

Second line chemotherapy in patients with enteropathy-associated T cell lymphoma: a retrospective single center analysis

Enteropathy-associated T cell lymphoma (EATL) is a rare disease with a dismal prognosis. Due to the low efficacy of chemotherapy and the poor performance status of patients failing first line, no data on second line therapy exist. A retrospective analysis of 19 patients with EATL at our institution identified six patients (31%) undergoing second line chemotherapy after CHOP-like regimens. Three patients had progressive disease (PD) during first line therapy, while the other three patients showed relapse after an initial complete remission (CR). The time from the last cycle of first line chemotherapy to second line therapy was 1-62 months. Two patients received ifosfamide, carboplatin and etoposide (ICE), two were given fludarabine and cyclophosphamide (FC) and one each had dexamethasone, cisplatin and cytarabine (DHAP) and cladribine chemotherapy. One patient progressed after one course of cladribine, while two patients developed intestinal perforation and died after one course of ICE and DHAP, respectively. Three patients achieved a CR lasting 4, +7 and +64 months, with two being alive without evidence of disease. Our data again confirm the poor prognosis of patients with EATL. A small subset of patients, however, apparently benefits from initiation of second line chemotherapy.

Predictors and impact of second-line chemotherapy for advanced non-small cell lung cancer in the United States: real-world considerations for maintenance therapy.

: Recent clinical trials incorporating maintenance chemotherapy into the initial treatment of advanced non-small cell lung cancer (NSCLC) have highlighted the benefits of exposing patients to second-line therapies. We, therefore, determined the predictors and impact of second-line chemotherapy administration in a contemporary, diverse NSCLC population. : We performed a retrospective analysis of consecutive patients diagnosed with stage IV NSCLC from 2000 to 2007 at clinical facilities associated with the University of Texas Southwestern Medical Center. Demographic, disease, treatment, and outcome data were obtained from hospital tumor registries. The association between these variables was assessed using univariate analysis and multivariate logistic regression. : A total of 406 patients in this cohort received first-line chemotherapy and were included in the analysis. Mean age was 59 years, 28% were women, and 59% were white. Among these patients, 197 (49%) received second-line chemotherapy. Among those patients who had not progressed after four to six cycles of first-line chemotherapy, 67% received second-line chemotherapy. Receipt of second-line chemotherapy was significantly associated with patient insurance type (p = 0.007), number of cycles of first-line chemotherapy (p < 0.001), and receipt of prechemotherapy palliative radiation therapy (p = 0.005) but was not associated with patient age, gender, race, histology, or year of diagnosis. In a multivariate model, second-line chemotherapy administration remained associated with insurance type (p = 0.003), number of cycles of first-line chemotherapy (p < 0.001), and receipt of prechemotherapy palliative radiation therapy (p = 0.008). The number of cycles of first-line chemotherapy and administration of second-line chemotherapy were associated with overall survival in both univariate and multivariate analyses. : In this unselected, contemporary, and diverse cohort of patients with advanced NSCLC, 67% of individuals whose disease had not progressed after four to six cycles of first-line chemotherapy eventually received second-line chemotherapy. Markers of socioeconomic status, symptom burden, and response to and tolerance of first-line chemotherapy were associated with receipt of second-line chemotherapy. These factors may assist in the selection of patients most likely to benefit from maintenance chemotherapy.

A double-blind, randomized placebo-controlled, phase II study of maintenance enzastaurin (ENZ) with 5-FU/leucovorin (LV) plus bevacizumab (BV) following first-line therapy for metastatic colorectal cancer (mCRC).

501 Background: Maintenance therapy is designed to maximize progression-free survival (PFS) and minimize toxicity in advanced CRC. ENZ is an oral serine/threonine kinase inhibitor that targets PKC-b and the AKT/PI3K pathway. Preclinical studies demonstrated synergistic antitumor effects when ENZ was combined with BV. In phase I studies, the combination was well tolerated. This phase II study assessed ENZ with 5-FU/LV plus BV as maintenance therapy for mCRC. Methods: Patients had locally advanced or mCRC, and completed 6 cycles of first-line chemotherapy ≤4 wks prior to randomization. Arm A received a loading dose of ENZ 1,125 mg, followed by 500 mg/d subsequent doses. Arm B received placebo. Both groups received 5-FU/LV (LV 400 mg/m2 IV, 5-FU 400 mg/m2 bolus, 5-FU 2,400 mg/m2 IV) plus BV 5 mg/kg IV, every 2 wks. Patients were treated with 5-FU/LV plus BV plus either ENZ or placebo until disease progression or for 1 yr. Primary endpoint was PFS from randomization. Secondary endpoints were overall survival (OS) from randomization, and OS and PFS from start of first-line therapy. Analysis was done after 50 events (objective or clinical progression). Results: 58 patients were randomized to Arm A (57 treated), 59 to Arm B (58 treated). 82 (70.1%) patients discontinued treatment (Arm A, 42 [72.4%]; Arm B, 40 [67.8%]), the majority due to disease progression. Median cycles were 9 in Arm A, 10 in Arm B. Median PFS in months was 5.8 in Arm A and 8.1 in Arm B (hazard ratio [HR]=1.35, 95% CI: 0.84, 2.16; protocol specified one-sided test, p=0.896). Median OS was not calculable due to high censoring (77.6% in Arm A and 91.5% in Arm B). Median PFS in months from start of first-line therapy was 8.9 in Arm A and 11.3 in Arm B (HR=1.39, 95% CI: 0.86, 2.23; one-sided, p=0.913). More patients developed thrombosis or embolism (TE), including pulmonary embolism, on Arm A (5 [8.8%] patients had grade 3 and 5 [8.8%] grade 4 TE) compared with Arm B (no grade 3 and 1 [1.7%] grade 4 TE). Conclusions: ENZ did not demonstrate an advantage in PFS compared to BV-based therapy alone. Further development of maintenance therapy with ENZ is not recommended for mCRC. [Table: see text]

Mid-Treatment Plasma Levels of Thymus Activated and Regulated Chemokine (TARC) Predict Treatment Outcome In Classical Hodgkin Lymphoma Patients

AbstractAbstract 748 Purpose:Thymus and Activation Regulated Chemokine (TARC) is highly expressed by the Hodgkin Reed Sternberg (HRS) tumor cells of classical Hodgkin lymphoma (cHL) in the vast majority of patients. This chemokine is released in the circulation and may serve as a cHL specific biomarker. We and others showed high serum levels of TARC before start of treatment and a significant decrease in serum TARC levels after treatment. The aim of the current study is to relate plasma TARC levels during treatment with response as observed by FDG-PET imaging in cHL patients. Patients and Methods:Sixty-three newly diagnosed cHL patients from the University Medical Center Groningen were included from 2005 until 2009. Patients were treated according to clinical trial (EORTC) or hospital protocols: 1st line treatment consisted of ABVD chemotherapy with or without involved node radiotherapy for stage I/II and ABVD or EscBEACOPP/BEACOPP chemotherapy for other stages. Plasma was collected before treatment and ideally also before start of every chemotherapy cycle, with at least a sample concurrent with mid-treatment FDG-PET evaluation and at completion of treatment. Plasma TARC levels were evaluated by ELISA. TARC expression in HRS cells was determined by immunohistochemistry (IHC) on tissue samples. Results:TARC staining was observed in the HRS cells in 95% of patients. Patients with negative TARC staining did not have elevated pre-treatment plasma TARC levels and were excluded from further analysis. Pre-treatment plasma TARC levels in stage II-IV disease were significantly higher compared to stage I disease (p < .001). Patients with bulky disease had significantly higher TARC values compared to patients without bulky disease (p = .04). Mid-treatment TARC was significantly elevated in 2 out of 54 patients with an available plasma sample (Figure 1). Mid-treatment FDG-PET was positive in 13/53 patients. Two patients had persistent mid-treatment FDG-PET activity in >2 nodes and these 2 patients were the only two patients with persistent high mid-treatment TARC. The other 11 mid-treatment FDG-PET positive patients only had residual FDG-PET positivity in 1 or 2 nodes and TARC was normalized in all 11 patients. Two of these 11 patients switched to EscBEACOPP dictated by the mid-treatment FDG-PET result since they were treated in the experimental arm of the EORTC H10 trial, while the 2 patients with >2 mid-treatment FDG-PET positive nodes and high TARC did not switch since they were treated in the standard arm of this trial. End-treatment TARC was significantly elevated in 2 out of 58 patients. 4/13 mid-treatment FDG-PET positive patients remained FDG-PET positive at end-treatment evaluation. The two patients with persistent activity in >2 nodes and high TARC at mid-treatment evaluation had progressive disease at end-treatment evaluation and TARC levels remained high. Of the 11 patients with mid-treatment FDG-PET positivity and low mid-treatment TARC, 9 became FDG-PET negative. Two patients (one of those who switched to EscBEACOPP) still had residual FDG-PET activity in the same spots at end-treatment evaluation while TARC remained low. The other patient proceeded to second line treatment but remained FDG-PET positive. However, both patients did not progress during 6 months follow-up without further treatment. Of note: after one cycle of first line chemotherapy we could already observe the same plasma TARC dynamics as observed at mid- and end-treatment evaluation (n=42, Figure 1). [Display omitted] Conclusion:Mid-treatment plasma TARC levels outperformed mid-treatment FDG-PET imaging in predicting response to therapy in primary cHL patients. Moreover, TARC levels after one chemotherapy cycle could already predict final response to treatment. Evaluation of TARC dynamics before and during treatment in future clinical trials is needed to confirm the prognostic value of plasma TARC in cHL patients. Disclosures:No relevant conflicts of interest to declare.

Do Patients With Platinum-Resistant Epithelial Ovarian Cancer Benefit From Second-line Chemotherapy?

Background: The survival benefit of second-line chemotherapy in the treatment of patients with platinum-resistant epithelial ovarian cancer has not yet been established. It is unclear whether these patients may benefit from second-line chemotherapy. Patients and Methods: This study included 51 consecutive patients with platinum-resistant cancer (interval between last chemotherapy cycle and detection of tumor recurrence or progressive disease < 6 months) who died between 1999 and 2008 at the National Cancer Center Hospital. To identify the factors associated with longer survival in such patients, the Cox proportional hazard model was used to perform multivariate analyses of factors influencing patient survival, including performance status (PS) and second-line chemotherapy. Results: In patients with platinum-resistant disease, the median progression-free interval from the last cycle of first-line chemotherapy to the time of detection of progressive disease was 46 days (range, 5-169 days); the median survival time after the detection of progressive disease was 5.6 months (range, 0.3-69.8 months). Patients who received second-line chemotherapy had significantly longer survival times than those who did not (6.3 months vs. 3.1 months; P = .0039). However, multivariate analyses revealed that PS was the only factor associated with survival (hazard ratio [HR], 0.267; 95% CI, 0.114-0.626; P < .0024). Exposure to second-line chemotherapy was not associated with survival (HR, 0.488; 95% CI, 0.3-2.0; P = .103). Conclusion: Good PS (< 2; not second-line chemotherapy) is the only factor associated with longer survival in patients with platinum-resistant ovarian cancer. Patients with a poor PS status (≥ 2) may not benefit from second-line chemotherapy.

Who Are Less Likely to Receive Subsequent Chemotherapy Beyond First-Line Therapy for Advanced Non-small Cell Lung Cancer?: Implications for Selection of Patients for Maintenance Therapy

Prospective studies have implied that maintenance therapy for non-small cell lung cancer (NSCLC) has its effect by giving active drugs earlier to patients who otherwise die without receiving second-line therapy. The purpose of this study was to select patients with NSCLC who could most benefit from maintenance therapy, by evaluating which patients would be less likely to receive second-line therapy. Clinicopathologic data of patients with advanced NSCLC who received four cycles of first-line chemotherapy followed by time-off therapy and eventual disease progression or death were reviewed retrospectively. Patients were grouped into ones with first-line therapy only or ones with more than first-line therapy. Clinical characteristics between the two groups were compared. A total of 271 patients were eligible for analysis, and 39 patients (14.4%) received only first-line therapy. Patients significantly more likely to receive only first-line therapy had performance status of two or three after first-line therapy, large volume of initial target lesions (sum of long diameters >or=70 mm), or smaller decrease in target lesions (decrease <20%) after first-line therapy. Median overall survival of the 143 patients (52.8%) with at least one of these characteristics (16.3 months) was significantly shorter than that of patients without any of these characteristics (23.5 months, p = 0.007). Maintenance therapy may be of greater benefit to patients with NSCLC who have clinical characteristics including poor performance status after first-line therapy, large initial target lesions, or smaller decrease in target lesions after first-line therapy.

Duration of Chemotherapy for Metastatic Non–Small-Cell Lung Cancer: More May Be Better After All

Non–small-cell lung cancer (NSCLC) is one of the few diseases for which numerous randomized clinical trials have compared best supportive care with chemotherapy. These studies have shown that compared with best supportive care, platin-based chemotherapy improves survival in patients with good performance status. Since these studies were performed, we have seen the impact of systemic therapy on survival, both in second-line (docetaxel, erlotinib, and pemetrexed) and third-line (erlotinib) recurrent disease settings. Despite the survival advantage observed with firstand secondline chemotherapy, most randomized studies to date have failed to show a definitive improvement in survival with the administration of additional first-line chemotherapy, although most have shown an improvement in progression-free survival (PFS), more often than not with a higher incidence of adverse events. As pointed out by Soon et al in this issue of Journal of Clinical Oncology, there are several ways to administer additional chemotherapy to patients who have responded or stabilized after four to six cycles of first-line chemotherapy. These include: first, continuing first-line chemotherapy until disease progression; second, continuing first-line chemotherapy, but limiting it to a specified number of cycles; and third, switching to a different regimen after a defined number of cycles of first-line chemotherapy. Various terms have been used to describe to these different scenarios. Some call the first and second approaches maintenance therapy and the third early second-line therapy, whereas others call the first and second approaches prolonged chemotherapy and the third induction chemotherapy followed by consolidation. Although there is no uniform consensus regarding terminology, early second-line therapy implies interval progression, and maintenance therapy implies continuation of original regimen, whereas consolidation implies switching to a different treatment. We prefer the terminology of maintenance for the first and second approaches and consolidation for the third. Regardless of the terminology, before the administration of additional chemotherapy can be adopted as part of routine practice, it is critically important to show a survival benefit, given the toxicities associated with chemotherapy in diseases with poor prognoses, such as lung cancer. Presumably, an improvement in PFS without an improvement in overall survival suggests that both the first and second regimens are active, and it does not matter when the second regimen is administered—at progression or immediately after the first regimen. Although this question of sequence has only been formally tested in one advanced NSCLC trial, it has been tested extensively in other malignancies, such as colorectal carcinoma and breast cancer. In reports of these studies, it has been argued that if PFS is improved without corresponding improvement in survival, the timing of administration of consolidation or second therapy does not matter; the second regimen could be delayed until progression. Regardless of the underlying mechanism, what is most important is that an approach works (ie, that it improves survival). In the absence of a clearcut survival advantage, it is hard to justify added expense or toxicity. However, several recent studies have suggested that there may be benefit in administering additional chemotherapy after four to six cycles of a front-line regimen. In the clinical trial in advanced NSCLC reported by Fidias et al, patients received gemcitabine and carboplatin as first-line therapy. Those without progression after four cycles of chemotherapy were randomly assigned to immediately receive an additional six cycles of docetaxel or to follow the standard of care, which was defined as no additional therapy until disease progression, at which point they received docetaxel. Median PFS with immediate docetaxel (5.7 months) was significantly longer (P .0001) than that with delayed docetaxel (2.7 months). Although there was a trend toward improved survival with immediate docetaxel (12.3 months) compared with delayed docetaxel (9.7 months), it did not quite reach statistical significance (P .0853). One reason for poorer survival in the delayed arm of the trial reported by Fidias et al may have been because many patients randomly assigned to receive delayed docetaxel at progression never received it. Whereas 145 (95%) of 153 patients randomly assigned to receive immediate docetaxel received at least one cycle of additional chemotherapy, only 98 (63%) of 156 patients randomly assigned to the delayed arm actually went on to receive docetaxel at progression. Thirty of the remaining 58 patients did not receive delayed docetaxel because of disease progression or death. Survival for the 98 patients in the delayed arm who actually received docetaxel was 12.5 months— identical to the 12.5-month survival of the 145 patients in the immediate arm. This discrepancy suggests that the trend toward improved survival in the immediate arm as a whole was simply a result of more patients being able to receive an active drug. Thus, early treatment may be better, not because it does a better job of killing cancer cells in the JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 27 NUMBER 20 JULY 1

What do patients think about CA-125 monitoring in the follow-up? Results from a multicenter trial in 1,060 patients with ovarian cancer

5522 Background: In the clinical day CA-125 monitoring is frequently used as a part of follow-up care for patients with ovarian cancer (OC). However, the potential benefit of CA-125 controls in the absence clinical symptoms are still unclear.There is little known about the expectations and preferences of patients with OC. Therefore we have initiated a multi-institutional survey. Methods: A semi-structered consisting 15 questions was developed in a pilot-study of 20 patients. After this validation all gynecological departments and gynecological-oncological practices were invited to participate in this trial using an anonynomous print version of the questionaire Results: Between December 2006 and December 2007 a total of 1,060 patients were enrolled. The median age of the patients was 58 years (range 16–87). 60% of the patients had primary ovarian cancer, 40% had relapsed ovarian cancer. Routine follow-up visits were mostly performed by gynaecologists in a gynaecological practice (56.9%) and in hospitals (49.5%). Patients were informed about the procedures and goals of cancer care predominantly after primary surgery (62.5%) and in 15.7% after last cycle of first-line chemotherapy. 7.7% declared that they were informed only at the first follow-up visit, 9.2% stated that they have never received any information about their cancer care management. According the patient´s opinion the main objective for the follow-up is the early detection of relapse and a prolongation of overall survival (95.8%). About more than 90% get CA-125 measurements. These were the procedures with highest anxiety but also the most important procedure for the patient. Finally, most patients (89%) were satisfied from their management of cancer care. Conclusions: The present study is the largest survey about cancer care so far and provides several important data for physician-patient communication concerning the follow-up management of patients OC. No significant financial relationships to disclose.

Treatment of Advanced Lung Cancer

Lung cancer is the number 1 cancer-cause of death in the United States. The majority of the lung cancer patients are diagnosed with advanced disease. Platinum-based doublet chemotherapy is the standard chemotherapy in the treatment of advanced non-small-cell lung cancer (NSCLC) though non-platinum-based chemotherapy is an alternative possibility. Monoclonal antibodies that inhibit the binding of vascular endothelial growth factors (VEGF), such as bevacizumab, or the epidermal growth factors (EGFR), such as cetuximab, have been shown to significantly prolonged overall survival (OS) in combination with platinum-based doublet chemotherapy in the first line treatment of NSCLC. The optimal number of cycles of first line chemotherapy is between 3 and 4. Maintenance therapy with noncross- resistant agents after first line treatment is still considered as investigational at this time. The oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI),erlotinib, has been approved for use as second line or beyond in the treatment of NSCLC based on superior survival benefit over best supportive care. NSCLC patients with EGFR activation mutations generally had better response to erlotinib and are generally found in Asian, never-smokers, females, and adenocarcinoma histology. Studies have shown that lung cancer in never-smokers is a clinical entity and had superior overall survival. Studies are underway to determine which patients will benefit from platinum-based chemotherapy. Randomized trials have shown that elderly patients or patients with performance status (PS) 2 also benefited from chemotherapy.

Phase II Study of Risk-Adapted Therapy of Newly Diagnosed, Aggressive Non-Hodgkin Lymphoma Based on Midtreatment FDG-PET Scanning

In newly diagnosed aggressive non-Hodgkin lymphoma (NHL), a positive midtreatment fluorine-18 fluorodeoxyglucose positron emission tomography (PET) scan often carries a poor prognosis, with reported 2-year event-free survival (EFS) rates of 0% to 30% after standard therapy. To determine the outcome of early treatment intensification for midtreatment PET-positive disease, a phase II trial of risk-adapted therapy was conducted. Fifty-nine newly diagnosed patients, 98% with B cell lymphoma, had PET/CT performed after 2 or 3 cycles of first-line chemotherapy. Those with negative PET on semiquantitative visual interpretation completed standard therapy. Those with positive PET received platinum-based salvage chemotherapy, high-dose therapy, and autologous stem cell transplantation (ASCT). Midtreatment PET was positive in 33 (56%); 28 received ASCT with an actuarial 2-year EFS of 75% (95% confidence interval, 60%-93%). On intention-to-treat analysis, 2-year EFS was 67% (53%-86%) in all PET-positive patients and 89% (77%-100%) in PET-negative patients. No association was found between the International Prognostic Index category and the midtreatment PET result. The favorable outcome achieved here in historically poor-risk patients warrants further, more definitive investigation of treatment modification based on early PET scanning.