Paclitaxel Plus Research Articles

Characterizing tumor responses from RAINBOW, a randomized phase III trial of ramucirumab (RAM) plus paclitaxel (PAC) vs placebo (PBO) plus PAC in patients (pts) with previously treated advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma.

45 Background: In RAINBOW, OS and PFS were improved for pts with previously treated gastric/GEJ adenocarcinoma in the RAM + PAC arm. Objective response rate was also significantly improved: 28% (92/330) RAM + PAC vs 16% (54/335) PBO + PAC (P =.0001). Timing and duration of responses and quality of life (QoL) are described. Methods: Patients were randomized 1:1 to RAM 8 mg/kg or PBO on days 1 and 15 + PAC 80 mg/m2 on days 1, 8, and 15 (28-day cycle). Radiographic assessment of disease per RECIST v1.1 and assessment of QoL with the EORTC QLQ-C30 were done at baseline and 6-wk intervals following the first dose of study therapy. Time to response (TTR) was the time from randomization to first tumor response (complete or partial). Duration of response (DoR) was the time from first tumor response to disease progression. A swimmer plot of DoR, survival, and status at study end was developed. Time-to-event curves were generated using the Kaplan-Meier method. Hazard ratio (HR) for DoR was generated from a stratified Cox model. QoL scores were classified as improved or worsened if change from baseline was ≥ 10 points (100-point scale), otherwise considered stable. Results: Median TTR was 6.7 wks (range 4.3-33.3) for RAM + PAC pts and 6.6 wks (5.1-37.1) for PBO + PAC pts. A detailed swimmer plot confirms a majority of RAM + PAC pts (58% [53/92]) and PBO + PAC pts (61% [33/54]) responded by the first 6-wk assessment. Of these responders, 11% (6/53) and 6% (2/33) were still responding at 12 mos. Median DoR was 4.4 mos (95% CI 4.1, 5.5) in the RAM + PAC arm and 2.8 mos (95% CI 2.1, 4.2) in the PBO + PAC arm (HR = 0.66, 95% CI 0.45, 0.97; P =.0332). At 6 wks, rates of improved/stable QoL scores among responders were similar between treatment arms and higher among the responders (73% RAM + PAC vs 74% PBO + PAC) than in the intent-to-treat population (53% vs 50%). Conclusions: Patients with advanced gastric/GEJ cancer not only showed an improved response rate with RAM + PAC, but responses were also more durable. For the majority of pts, response occurred within the first 6 wks of therapy and was associated with QoL benefit. Clinical trial information: NCT01170663.

Clinical Analysis of Efficacy of Albumin Bound Paclitaxel Plus Platinum Compounds and Gemcitabine Plus Platinum Compounds as First-Line Chemotherapy for Advanced Squamous Non-Small Cell Lung Cancer

Clinical Analysis of Efficacy of Albumin Bound Paclitaxel Plus Platinum Compounds and Gemcitabine Plus Platinum Compounds as First-Line Chemotherapy for Advanced Squamous Non-Small Cell Lung Cancer

Everolimus plus exemestane versus bevacizumab-based chemotherapy for second-line treatment of hormone receptor-positive metastatic breast cancer in Greece: An economic evaluation study.

BackgroundThe objective of our study was to conduct a cost-effectiveness (CE) study of combined everolimus (EVE) and exemestane (EXE) versus the common clinical practice in Greece for the treatment of postmenopausal women with HR+/HER2- advanced breast cancer (BC) progressing on nonsteroidal aromatase inhibitors (NSAI). The combinations of bevacizumab (BEV) plus paclitaxel (PACL) and BEV plus capecitabine (CAPE) were selected as comparators.MethodA Markov model, consisting of three health states, was used to describe disease progression and evaluate the CE of the comparators from a third-party payer perspective over a lifetime horizon. Efficacy and safety data as well as utility values considered in the model were extracted from the relevant randomized Phase III clinical trials and other published studies. Direct medical costs referring to the year 2014 were incorporated in the model. A probabilistic sensitivity analysis was conducted to account for uncertainty and variation in the parameters of the model. Primary outcomes were patient survival (life-years), quality-adjusted life years (QALYs), total direct costs and incremental cost-effectiveness ratios (ICER).ResultsThe discounted quality-adjusted survival of patients treated with EVE plus EXE was greater by 0.035 and 0.004 QALYs, compared to BEV plus PACL and BEV plus CAPE, respectively. EVE plus EXE was the least costly treatment in terms of drug acquisition, administration, and concomitant medications. The total lifetime cost per patient was estimated at €55,022, €67,980, and €62,822 for EVE plus EXE, BEV plus PACL, and BEV plus CAPE, respectively. The probabilistic analysis confirmed the deterministic results.ConclusionOur results suggest that EVE plus EXE may be a dominant alternative relative to BEV plus PACL and BEV plus CAPE for the treatment of HR+/HER2- advanced BC patients failing initial therapy with NSAIs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12913-015-0971-4) contains supplementary material, which is available to authorized users.

Abstract 2691: Role of trastuzumab in the combination treatment for a HER2-positive trastuzumab-resistant gastric cancer xenograft model

Abstract Objective: Trastuzumab (Tras) resistance is an important clinical problem to be resolved for HER2-positive gastric cancers (GC). Even after the tumor develops resistance to Tras, continuous anti-HER2 therapies, including Tras with chemotherapy (Tras beyond PD) or trastuzumab emtansine (T-DM1), could be effective treatment options. The Tras-sensitive cell line GLM-1 was established from a liver metastasis of a GC patient (Nakanishi et al. 2005), and the Tras-resistant cell line GLM1-HerR2 (R2) was established from GLM-1 by in vivo selection (Oshima et al. 2014). In this study, we used GLM1 and R2 xenograft models to examine the Tras-resistant mechanism of R2 and the effects of Tras plus paclitaxel (PTX) or T-DM1. Methods: BALB/c-nu/nu mice subcutaneously inoculated with GLM1 or R2 received Tras (40 mg/kg, qw) intraperitoneally, PTX (15 mg/kg, qw) or T-DM1 (10-40 mg/kg, q3w) intravenously (Day 1). Tumor volume (TV) was measured to evaluate antitumor effects, HercepTest® was used for HER2 status, and flow cytometry to analyze Tras-binding ability. Cell proliferation after knockdown of HER family receptors was measured by BrdU incorporation. Signal transduction was examined by Western blot for tumors excised on Days 2 and 5. Results: In contrast to GLM-1, R2 showed resistance to Tras treatment in xenograft experiments. There were no clear differences in HER2 score (3+), Tras-binding ability, p-HER2, p-HER3, p-AKT levels, or PIK3CA status (no hot spot mutation). Effects of gene knockdown of EGFR/HER2/HER3 in GLM-1 and R2 on cell proliferation were similar (ca. 10%/50%-60%/10% reduction, respectively). In GLM-1 tumors, Tras treatment decreased p-AKT, increased p27 protein, and decreased p-Rb, resulting in G1 cell cycle arrest, whereas in the R2 tumors changes in those molecules were few. These results suggest that escape from Tras-induced G1 arrest could be a resistant mechanism of R2. Based on the above results, and because in R2 cells HER2 remained a driver of proliferation and mitotic arrest was maintained, we hypothesized that Tras + PTX would show a higher antitumor effect than PTX alone. In the R2 xenograft model on Day 22, the Tras + PTX group showed a significantly higher antitumor activity (TV: 2 ± 3 mm3) than the PTX alone group (TV: 208 ± 209 mm3). In tumor specimens from the PTX and Tras + PTX groups, p-histon H3 (an M phase marker) was increased on Day 2. However, the Tras + PTX group, unlike the PTX group, showed markedly decreased p-histon H3 on Day 5, which suggests that Tras in combination with PTX enhances apoptosis in R2 tumors. Interestingly, T-DM1 showed dose-dependent antitumor activity in both GLM-1 and R2 xenografts. Conclusion: It was indicated that continuous anti-HER2 treatment, including Tras with chemotherapy or T-DM1 monotherapy, could be efficacious treatments for HER2-positive Tras-resistant GC tumors that emerge during previous Tras treatment. Citation Format: Sei Shu, Yoriko Yamashita-Kashima, Mieko Yanagisawa, Yoichiro Moriya, Naoki Harada. Role of trastuzumab in the combination treatment for a HER2-positive trastuzumab-resistant gastric cancer xenograft model. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2691. doi:10.1158/1538-7445.AM2015-2691

RAINBOW: A global, phase 3, double-blind study of ramucirumab (RAM) plus paclitaxel (PTX) versus placebo (PL) plus PTX in the treatment of advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy—An age-group analysis.

11 Background: RAM is a human IgG1 monoclonal antibody VEGF-R2 antagonist. The RAINBOW trial demonstrated that RAM added to PTX significantly improved overall survival (OS), progression free survival (PFS), and objective response rates (ORR) in 2nd-line gastric and GEJ adenocarcinoma patients (pts). Outcomes are reported by pts aged <65 and ≥65 yrs. Methods: Pts with advanced gastric and GEJ adenocarcinoma after disease progression on platinum- and fluoropyrimidine-based chemotherapy were randomized 1:1 to receive RAM (8 mg/kg) or placebo (PL) on days 1 and 15 plus PTX 80 mg/m2IV on days 1, 8, and 15 of a 28-day cycle. Eligible pts had ECOG PS ≤ 1 and adequate organ function. OS was the primary endpoint. Secondary endpoints included PFS, ORR, and safety. Results: Baseline characteristics were generally well balanced. Outcomes are summarized in the Table. The incidence of Grade ≥3 adverse events (AEs) was higher in the RAM+PTX arms for both age groups and similar across age groups. Grade ≥3 AEs occurring in ≥10% of pts and at higher rate in the RAM+PTX arm, and febrile neutropenia are shown in the Table. Conclusions: RAM+PTX conferred similar improvements over PL+PTX for OS, PFS, and ORR in both age groups. Toxicity profiles were similar in both groups, although a relatively higher incidence of Grade ≥3 neutropenia and leukopenia in pts ≥65 years was noted. [Table: see text]

354PD - Cost Effectiveness Analysis of Everolimus Plus Exemestane Vs. Bevacizumab Plus Paclitaxel and Bevacizumab Plus Capecitabine for the Management of Postmenopausal Women with Er+ Breast Cancer

ABSTRACT Aim: Background: Estrogen receptor positive (ER+) metastatic breast cancer patients progressing on nonsteroidal aromatase inhibitors are candidates for treatment with everolimus (EVE) plus exemestane (EXE) or with chemotherapy. The aim of the study was to conduct a cost-effectiveness analysis (CEA) of EVE plus EXE versus bevacizumab (BEV) plus paclitaxel (PACL) and BEV plus capecitabine (CAPE) for the management of postmenopausal women with ER+ breast cancer from the perspective of the Greek National Health System. Methods: A Markov model, consisting of three health states, was used to describe disease progression and evaluate the CE of comparators. The model evaluated the comparators over a lifetime horizon in the course of a 1-month cycle from a third-party payer perspective. Efficacy, safety and utility data considered in the model were extracted from randomized Phase III clinical trials. Direct medical costs used reflecting the year 2013. Probabilistic sensitivity analysis was also conducted. Primary outcomes were quality-adjusted life years (QALYs) and total lifetime costs. Results: Discounted survival and quality adjusted survival of EVE plus EXE treated patients was higher compared to BEV plus PACL by 0.28 life-years and 0.19 QALYs, respectively, and by 0.21 life-years and 0.16 QALYs when compared to BEV plus CAPE. EVE plus EXE was the less costly treatment in terms of drug acquisition, administration and concomitant medications. The total lifetime cost per patient for EVE plus EXE was estimated at e46,251, for BEV plus PACL at e53,422 and for BEV plus CAPE at 50,619 e. The higher drug acquisition and administration cost of BEV plus PACL (EVE plus EXE: 16,956 e vs. BEV plus PACL: 22,379 e) partially explained the higher total lifetime cost over EVE plus EXE. Moreover, the higher pre-progressed costs of the BEV plus CAPE arm accounted for the largest part of the difference in the total lifetime cost between BEV plus CAPE and EVE plus EXE. Probabilistic analysis confirmed the results. Conclusions: Results suggest that EVE plus EXE may be a dominant (more effective and less costly) alternative relative to BEV plus PACL and BEV plus CAPE in the treatment of ER+ mBC patients failing initial therapy with NSAIs. Disclosure: G. Kourlaba: received funding from Novartis Hellas SA in order to perform the current cost-effectiveness analysis; M. Chatzikou: is employee of Novartis Hellas SA. All other authors have declared no conflicts of interest.

O-0006 - Rainbow: A Global, Phase 3, Double-Blind Study of Ramucirumab Plus Paclitaxel Versus Placebo Plus Paclitaxel in the Treatment of Gastric Cancer Following Disease Progression: Western Population Subgroup

Introduction: RAINBOW, a global, placebo-controlled, double-blind, phase III trial, demonstrated significant improvements in overall survival (OS) (hazard ratio (HR) 0.807; 95% CI 0.678, 0.962; p = 0.0169), progression-free survival (PFS) (HR 0.635; 95%CI 0.536, 0.752; p < 0.0001), and response rates (ORR 27.9% RAM + PTX;16.1 PTX p= 0.0001) in advanced gastric or GEJ adenocarcinoma patients receiving ramucirumab (RAM), a human IgG1 VEGF receptor 2 targeted antibody, plus paclitaxel (PTX). We present the pre-planned subgroup analysis of Western patients (Region 1).

RAINBOW: A global, phase III, randomized, double-blind study of ramucirumab (RAM) plus paclitaxel (PTX) versus placebo (PL) plus PTX in the treatment of metastatic gastroesophageal junction and gastric adenocarcinoma (mGC) following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy—Efficacy analysis in Japanese and Western patients.

4005 Background: RAINBOW, a global phase III trial, demonstrated significant improvements in overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) in patients (p...

The Multicenter, Phase II Prospective Study of Paclitaxel Plus Capecitabine as First-Line Chemotherapy in Advanced Gastric Carcinoma

The efficacy and toxicity of paclitaxel plus capecitabine (PX) as first-line treatment in advanced gastric cancer (AGC) was evaluated. Patients with previously untreated AGC were included. PX was given every 3 weeks until a maximum of six cycles or progression. Capecitabine monotherapy was continued for patients without disease progression. The primary endpoint was progression-free survival, and secondary endpoints were objective response rate, overall survival (OS), and safety. Overall, 194 patients were treated per protocol and one patient was excluded because of allergy to paclitaxel. Response was evaluated in 175 patients, with an objective response rate of 34.8%. After a median follow-up of 33.2 months, disease progression was observed in 141 patients, 137 died, and 16 were lost to follow-up, with progression-free survival of 188 days and OS of 354 days. In multivariate Cox regression analysis, no factor remained an independent predictor of OS. Forty-five patients who received capecitabine monotherapy after PX had longer OS (531 days). Adverse events were mild (Fig. 1), and the most common grade 3-4 toxicities were leucopenia and neutropenia. PX as a first-line treatment has promising efficacy in AGC. Based on these data, a phase III study has been launched for further investigation.

Updated Results of a Phase 2 Study of Biweekly Dose-Intense Paclitaxel Plus Gemcitabine (GEM/TAX) in Patients With Recurrent Locoregional or Metastatic Head-and-Neck Squamous Cell Carcinoma: Management of Recurrent Head-and-Neck Squamous Cell Carcinoma

Patients (pts) with metastatic head and neck squamous cell carcinoma (HNSCC) have a poor prognosis, limited treatment options, and median survival of 6 to 9 months. Paclitaxel (TAX) and gemcitabine (GEM) have both shown activity in HNSCC. We have reported on a phase 2 trial of the efficacy and safety of biweekly dose-intense GEM/TAX in patients with recurrent locoregional or metastatic HNSCC (Sukari et al ESMO 2012). Now with censoring rates of only 33% and 0% for progression-free survival (PFS) and overall survival (OS), respectively, we report the updated results of that trial.

Efficacy of first-line bevacizumab (BEV)-based therapy for metastatic triple-negative breast cancer (TNBC): Subgroup analysis of TURANDOT.

1040 Background: The randomized phase III TURANDOT trial compared first-line BEV plus paclitaxel (PAC) vs BEV plus capecitabine (CAP) in HER2-negative metastatic BC (mBC). BEV-based regimens are often favored in TNBC [Dawood 2012] because of efficacy in subgroup analyses and a lack of effective treatments. We performed an exploratory subgroup analysis of TURANDOT to provide more data on BEV-based therapy in TNBC. Methods: Patients (pts) with HER2-negative mBC who had received no prior chemotherapy for mBC were randomized to either BEV–PAC (BEV 10 mg/kg d1 and 15 + PAC 90 mg/m2 d1, 8, and 15 q4w) or BEV–CAP (BEV 15 mg/kg d1 + CAP 1000 mg/m2bid d1–14 q3w). The primary endpoint was overall survival (OS); secondary endpoints included objective response rate (ORR), progression-free survival (PFS), and safety. Results: Of 561 pts treated, 130 had TNBC. Baseline characteristics were typical of a poor-prognosis population and generally balanced between treatment arms, although fewer pts receiving BEV–PAC than BEV–CAP had ECOG PS 1/2 (25% vs 40%, respectively), positive lymph nodes (56% vs 72%), metastatic disease at first diagnosis (19% vs 30%), and liver metastases (27% vs 43%). Median age was 54 vs 56 years, respectively. At data cut-off, median follow-up was 21.4 vs 19.2 mo for BEV–PAC and BEV–CAP, respectively. The safety profiles in the TNBC subgroup were similar to the overall population. The predominant grade ≥3 AEs were hematologic AEs and neuropathy with BEV–PAC and hand-foot syndrome and diarrhea with BEV–CAP. Conclusions: One-year OS rates up to 78% in TURANDOT are among the highest seen in TNBC. BEV-based therapy is a valid option in a setting with limited active treatments. BEV–PAC may be favored based on 1-year OS, PFS, and ORR. Clinical trial information: NCT00600340. [Table: see text]

Randomized Phase II Study of Ixabepilone or Paclitaxel Plus Carboplatin in Patients With Non–Small-Cell Lung Cancer Prospectively Stratified by Beta-3 Tubulin Status

Retrospective studies have reported that tumor expression of the beta-3 tubulin (β3T) isoform is an unfavorable prognostic factor in non-small-cell lung cancer (NSCLC) treated with tubulin-inhibiting chemotherapy. Ixabepilone is a tubulin-inhibiting agent with low susceptibility to multiple resistance mechanisms including β3T isoform expression in several tumor models. This randomized phase II study evaluated ixabepilone-based chemotherapy in stage IIIb/IV NSCLC, compared with paclitaxel-based chemotherapy. Tumor specimens were prospectively evaluated for β3T expression. Patients were stratified by β3T status (positive v negative) and randomly assigned at a ratio of 1:1 to receive ixabepilone (32 mg/m(2)) and carboplatin (area under concentration-time curve [AUC], 6) or paclitaxel (200 mg/m(2)) and carboplatin (AUC, 6) for up to six cycles. The primary end point was progression-free survival (PFS) in the β3T-positive subgroup. Ninety-five patients (β3T positive, 52; β3T negative, 43) received ixabepilone plus carboplatin; 96 patients (β3T positive, 49; β3T negative, 47) received paclitaxel plus carboplatin. No significant differences in median PFS were observed between arms for either subgroup (β3T positive, 4.3 months in both arms; β3T negative, 5.8 v 5.3 months). Ixabepilone did not significantly improve overall survival (OS) for the β3T-positive subset or the overall population. Adverse events were similar between the two arms and comparable with those in previous studies. There was no predictive value of β3T in differentiating clinical activity of ixabepilone- or paclitaxel-containing regimens. Ixabepilone did not improve PFS or OS in patients with β3T-positive tumors. β3T-positive patients had worse PFS relative to β3T-negative patients, regardless of treatment; hence, β3T expression seems to be a negative prognostic factor, but not a predictive factor, in advanced NSCLC treated with either ixabepilone or paclitaxel platinum-based doublets.

再発巣照射後bevacizumab併用化療にて出血制御不能となった乳癌の1例

再発巣照射後bevacizumab併用化療にて出血制御不能となった乳癌の1例

1043P - Phase II Study of Biweekly Dose-Intense Paclitaxel Plus Gemcitabine (GEM/TAX) in Patients with Recurrent Locoregional or Metastatic Head and Neck Squamous Cell Carcinoma

ABSTRACT Background Patients with metastatic head and neck squamous cell carcinoma (HNSCC) have a poor prognosis, limited treatment options, and median survival of 6 to 9 months. Paclitaxel (TAX) and gemcitabine (GEM) have both shown activity in HNSCC. The optimal combination, dosing, and scheduling of both drugs is, however, unknown. Thus, we investigated the efficacy and safety of biweekly dose-intense GEM/TAX in patients with recurrent locoregional or metastatic HNSCC. Methods An open-label, single-institution, single-arm, phase II study was conducted for patients (pts) who were previously treated with no more than two cytotoxic regimens. The pts received paclitaxel (150 mg/m2IV) and gemcitabine (3000 mg/m2 IV) on day 1 and 15. The treatments were repeated every 28 days (one cycle), until disease progression or unacceptable toxicity. The primary end point was response rate. RECIST-defined response was evaluated every 2 cycles (8 wks) and toxicities were evaluated after each cycle (4 wks). Results Fifty-five pts were enrolled into the trial (M: F 42:13, median age (range): 56 years (23-84), performance status 0-2, 48 pts had previous radiation therapy and 39 had previous surgery), 41 of whom were response evaluable. Of these 41 patients, two pts (4.8%) achieved complete response (CR) and 17 (41.4%) demonstrated a partial response (PR). Thus, the overall response rate was 46%. Thirteen pts (31.7%) had stable disease (SD), resulting in tumor control in 32 of 41 pts (78% with CR, PR or SD), whereas 9 pts (21.1%) had disease progression (PD). Among those pts who achieved objective response or stable disease, the median response duration was 5 months and median time to progression was 4 months. Median overall survival (OS) was 15 months. Myelosuppression was the most common adverse event. Grade 3-4 neutropenia and anemia were observed in 5 (12%) and 11 (26%) pts, respectively. Eight (19%) pts developed grade 3 infection. None of these pts, however, had febrile neutropenia and there were no treatment-related deaths. Conclusions The combination of biweekly dose intense GEM/TAX was tolerable and active regimen in patients with recurrent locoregional or metastatic HNSCC. Our findings warrant further investigation in a larger patient population. Disclosure All authors have declared no conflicts of interest.

Weekly nab-Paclitaxel in Combination With Carboplatin Versus Solvent-Based Paclitaxel Plus Carboplatin as First-Line Therapy in Patients With Advanced Non–Small-Cell Lung Cancer: Final Results of a Phase III Trial

This phase III trial compared the efficacy and safety of albumin-bound paclitaxel (nab-paclitaxel) plus carboplatin with solvent-based paclitaxel (sb-paclitaxel) plus carboplatin in advanced non-small-cell lung cancer (NSCLC). In all, 1,052 untreated patients with stage IIIB to IV NSCLC were randomly assigned 1:1 to receive 100 mg/m(2) nab-paclitaxel weekly and carboplatin at area under the concentration-time curve (AUC) 6 once every 3 weeks (nab-PC) or 200 mg/m(2) sb-paclitaxel plus carboplatin AUC 6 once every 3 weeks (sb-PC). The primary end point was objective overall response rate (ORR). On the basis of independent assessment, nab-PC demonstrated a significantly higher ORR than sb-PC (33% v 25%; response rate ratio, 1.313; 95% CI, 1.082 to 1.593; P = .005) and in patients with squamous histology (41% v 24%; response rate ratio, 1.680; 95% CI, 1.271 to 2.221; P < .001). nab-PC was as effective as sb-PC in patients with nonsquamous histology (ORR, 26% v 25%; P = .808). There was an approximately 10% improvement in progression-free survival (median, 6.3 v 5.8 months; hazard ratio [HR], 0.902; 95% CI, 0.767 to 1.060; P = .214) and overall survival (OS; median, 12.1 v 11.2 months; HR, 0.922; 95% CI, 0.797 to 1.066; P = .271) in the nab-PC arm versus the sb-PC arm, respectively. Patients ≥ 70 years old and those enrolled in North America showed a significantly increased OS with nab-PC versus sb-PC. Significantly less grade ≥ 3 neuropathy, neutropenia, arthralgia, and myalgia occurred in the nab-PC arm, and less thrombocytopenia and anemia occurred in the sb-PC arm. The administration of nab-PC as first-line therapy in patients with advanced NSCLC was efficacious and resulted in a significantly improved ORR versus sb-PC, achieving the primary end point. nab-PC produced less neuropathy than sb-PC.

Factors Exacerbating Peripheral Neuropathy Induced by Paclitaxel Plus Carboplatin in Non-small Cell Lung Cancer

No established supportive therapy to prevent and treat chemotherapy-induced peripheral neuropathy (PN) is available. Minimizing the severity of PN is therefore critical in clinical use. We aimed to determine when and how often PN occurs in association with paclitaxel plus carboplatin (PC therapy), a regimen used to treat non-small cell lung cancer, and factors that exacerbate this condition. Patients who received PC therapy for non-small cell lung cancer at the Japanese Foundation for Cancer Research, Cancer Institute Hospital, between May 20, 2009, and November 30, 2010, were included. PN was evaluated by the study pharmacist using specific questions based on the Common Terminology Criteria for Adverse Events Version 3.0. Univariate analysis was used to compare a group with no, Grade 1, or Grade 2 PN (non-serious) and a group with Grade 3 PN (serious). Analyses were conducted using the Cox proportional hazard model with patient characteristics having p < or = 0.20 when assessed as independent variables. Of 50 patients, 38 (76.0%) developed PN by day 6 of the first course of anticancer treatment. Grade 3 PN had an incidence of 25.0% in the fourth course. In multivariate analysis with the Cox proportional hazard model, pack-year [hazard ratio = 1.029; 95% confidence interval (CI): 1.009-1.050, p = 0.005] and creatinine clearance (hazard ratio = 0.957; 95% CI: 0.920-0.996, p = 0.031) were significant factors. A high pack-year and a low creatinine clearance exacerbated PN in patients treated with PC. PN must be carefully evaluated in patients with exacerbating factors.

439 Significantly Higher Pathologic Complete Response Rate with Weekly Compared with Three-weekly Paclitaxel and Carboplatin Plus Trastuzumab Neoadjuvant Therapy – Results of a Randomized Trial in Human Epidermal Growth Factor Receptor 2-positive Breast Cancer

439 Significantly Higher Pathologic Complete Response Rate with Weekly Compared with Three-weekly Paclitaxel and Carboplatin Plus Trastuzumab Neoadjuvant Therapy – Results of a Randomized Trial in Human Epidermal Growth Factor Receptor 2-positive Breast Cancer

Weekly nab-Paclitaxel in Combination With Carboplatin Versus Solvent-Based Paclitaxel Plus Carboplatin as First-Line Therapy in Patients With Advanced Non–Small-Cell Lung Cancer: Final Results of a Phase III Trial

Weekly nab-Paclitaxel in Combination With Carboplatin Versus Solvent-Based Paclitaxel Plus Carboplatin as First-Line Therapy in Patients With Advanced Non–Small-Cell Lung Cancer: Final Results of a Phase III Trial

Induction Pemetrexed and Cisplatin Followed by Maintenance Pemetrexed Versus Carboplatin Plus Paclitaxel Plus Bevacizumab Followed by Maintenance Bevacizumab: A Quality of Life–Oriented Randomized Phase III Study in Patients With Advanced Non-Squamous Non–Small-Cell Lung Cancer (ERACLE)

In advanced non–small-cell lung cancer (NSCLC), substantial similarities in terms of treatment efficacy and survival have emerged over the years between the different systemic chemotherapy regimens used. More recently, other topics such as histotype, maintenance therapy and quality of life have been explored to ameliorate this plateau. We present the treatment rationale and study design of the ERACLE (induction pEmetrexed and cisplatin followed by maintenance pemetRexed versus cArboplatin-paCLitaxel and bEvacizumab followed by maintenance bevacizumab) trial. Patients enrolled in the ERACLE trial are randomized between combination treatment arms: (A) cisplatin 75 mg/m2 day 1 and pemetrexed 500 mg/m2 day 1, every 3 weeks for six cycles followed (in responders or with stable disease) by pemetrexed 500 mg/m2 day 1, every 3 weeks until progression; and (B) carboplatin AUC 6 day 1, plus paclitaxel 200 mg/m2 day 1 and plus bevacizumab 15 mg/kg, every 3 weeks for six cycles followed (in responders or patients with stable disease) by bevacizumab 15 mg/kg every 3 weeks until progression. The primary objective of the study is to evaluate the difference in terms of quality of life between treatment arms. together with co-primary endpoints represented by the EuroQoL group (EQ-5D) questionnaire total score and the EQ-5D visual analog scale. Secondary endpoints are the evaluation of treatment activity and exploratory evaluation of treatment efficacy.

Phase II Study of Biweekly Paclitaxel Plus Infusional 5-Fluorouracil and Leucovorin as First-Line Chemotherapy in Patients With Advanced Gastric Cancer

This study was conducted to evaluate the efficacy and safety of combination chemotherapy with biweekly paclitaxel plus infusional 5-fluorouracil (5-FU) and leucovorin as first-line treatment for patients with advanced gastric cancer. Eligible patients with histologically confirmed advanced or metastatic gastric cancer were enrolled. The chemotherapeutic regimen consisted of paclitaxel (100 mg/m(2) on day 1) as a 3-hour intravenous infusion, followed sequentially by leucovorin (400 mg/m(2) on day 1) as a 2-hour intravenous infusion, bolus 5-FU (400 mg/m(2) on day 1), and then continuous infusion 5-FU (3000 mg/m(2) on day 1) over 46 hours. Cycles were repeated every 2 weeks. Sixty patients were enrolled (median age, 52.5 years old). Of these, 65% patients had Eastern Cooperative Oncology Group performance status of grade 2. A median of 8 cycles was administered (range, 4-12). Fifty-five patients were evaluable for response. Two patients achieved a complete response and 28 patients achieved a partial response, producing an overall response rate of 50% by intent-to-treat analysis. The median duration of response was 6.4 months (95% CI, 5.14-7.60 months). Median progression-free survival and median overall survival were 7.7 months (95% CI, 6.5-8.9 months) and 14.3 months (95% CI, 9.4-19.1 months), respectively. Hematologic toxicity was mild; grade 3 neutropenia was noted in only 6.7% of patients. Alopecia was the most common nonhematologic toxicity in 51 patients (71.4%). Grade 3 alopecia occurred in 11 patients (18.3%). Combination chemotherapy of biweekly paclitaxel followed sequentially by infusion leucovorin, bolus 5-FU, and continuous infusion 5-FU over 46 hours is effective and well tolerated in patients with advanced gastric cancer, especially in patients with poor performance status who cannot tolerate aggressive chemotherapy regimens.