Paclitaxel Plus Research Articles

Dose-Dense Paclitaxel Plus Carboplatin (PCdd) versus Epirubicin and Cyclophosphamide (ECdd) Followed by Paclitaxel (P) As Adjuvant Chemotherapy in Early Triple-Negative Breast Cancer at High Risk of Recurrence, A Randomised, Open-Label, Phase 3 Trial

Background: Triple-negative breast cancer (TNBC) may be more sensitive to platinum-based regimens. This open-label, randomized phase III trial aimed to compare dose dense paclitaxel plus carboplatin (PCdd) with dose-dense epirubicin and cyclophosphamide followed by paclitaxel (ECdd-P) regimen as adjuvant chemotherapy (AC) for high-risk early TNBC. Methods: We included Chinese patients with high recurrence risk TNBC who underwent primary breast surgery. They were randomly assigned in a 1:1 ratio to receive PCdd (paclitaxel 150 mg/m2 on day 1 and carboplatin AUC=3 on day 2 for 8 cycles) or ECdd-P (epirubicin 80 mg/m2 divided in 2 days and cyclophosphamide 600 mg/m2 on day 1 for 4 cycles followed by paclitaxel 175 mg/m2 on day 1 for 4 cycles) every 2 weeks, with granulocyte colony-stimulating factor (G-CSF) support. The primary endpoint was 3-year disease-free survival (DFS); the secondary endpoints were overall survival (OS) and safety. Findings: The intent-to-treat population included 143 patients (70 in the PCdd arm and 73 in the ECdd-P arm). Compared with the ECdd-P arm, the PCdd arm had significantly higher 3-year DFS (93⋅9% vs.79⋅1%, hazard ratio[HR]=3⋅224, 95% confidence interval [CI] =1⋅420-7⋅321, log-rank p=0⋅0051) and OS (98⋅5% vs.92⋅9% [HR] =7⋅092, 95% CI=1⋅212-16⋅630, log-rank p=0⋅0281). The 3-year DFS in the PCdd arm was significantly higher (p 40 years, Ki-67>30, and clinically evaluated lymph nodes. Both regimens were well tolerated. Worse neutropenia (grade 3/4) was found in the ECdd-P arm (47⋅9% vs. 21⋅4%, p=0⋅001). Interpretation: PCdd was superior to ECdd-P as AC for early TNBC with respect to improving the 3-year DFS and OS. PCdd also yields lower hematological toxicity.Thus, PCdd might be a preferred AC regimen for early TNBC patients with high recurrence risk. Trial Registration: This trial is registered at ClinicalTrials. gov (number NCT01378533). Funding Statement: This study was supported by National Key Research and Development Program of China (2018YFC1312101); and Chinese Academy of Medical Science Initiative funded this study for Innovative Medicine (CAMS-12M-1-010). Declaration of Interests: All authors declare no conflicts of interest. Ethics Approval Statement: All interventions were performed in accordance with Chinese laws and regulations and the Helsinki declaration. The study protocol was approved by the independent ethics board committee at the National Cancer Center, Chinese Academy of Medical Sciences (Approval number: CH-BC-012).

Effect of First-line S-1 Plus Oxaliplatin With or Without Ramucirumab Followed by Paclitaxel Plus Ramucirumab on Advanced Gastric Cancer in East Asia

Ramucirumab, a human IgG 1 antibody against vascular endothelial growth factor receptor 2, has been shown to improve progression-free survival and overall survival in patients with advanced gastric cancer in the second-line setting. To compare progression-free survival for S-1 and oxaliplatin plus ramucirumab with that for S-1 and oxaliplatin plus placebo in patients with advanced gastric cancer. This phase 2, double-blind randomized clinical trial (RAINSTORM [First-line S-1 Plus Oxaliplatin With or Without Ramucirumab Followed by Paclitaxel Plus Ramucirumab in Patients With Advanced Gastric Cancer]) was conducted from October 12, 2015, to April 11, 2018, at 36 sites in Japan, South Korea, and Taiwan. Participants were chemotherapy-naive patients (n = 189) with metastatic gastric or gastroesophageal adenocarcinoma. Analyses of the full analysis set and safety population were conducted between November 27, 2017, and June 4, 2018. Patients randomized to the ramucirumab plus S-1 and oxaliplatin arm received S-1, 80 to 120 mg/d twice daily, on days 1 to 14 and oxaliplatin, 100 mg/m2, on day 1 with ramucirumab, 8 mg/kg, on days 1 and 8 in part A (21-day cycle). Patients randomized to the placebo plus S-1 and oxaliplatin arm received the same S-1 and oxaliplatin dosage as well as placebo on days 1 and 8 in part A. Eligible patients received second-line paclitaxel, 80 mg/m2, on days 1, 8, and 15 and ramucirumab, 8 mg/kg, on days 1 and 15 in part B (28-day cycle). The primary end point was progression-free survival, analyzed using the stratified log-rank test; the hazard ratio (HR) was estimated using the stratified Cox proportional hazards regression model. Secondary end points included overall survival and adverse events. In total, 189 patients were randomized and received treatment: 96 to the ramucirumab plus S-1 and oxaliplatin arm and 93 to the placebo plus S-1 and oxaliplatin arm. Among the 189 patients, 121 (64.0%) were male, and the median (range) age was 62.0 (26-84) years. Median progression-free survival was not prolonged in the ramucirumab plus S-1 and oxaliplatin arm compared with the placebo plus S-1 and oxaliplatin arm (6.34 [80% CI, 5.65-6.93] vs 6.74 [80% CI, 5.75-7.13] months; HR, 1.07; 80% CI, 0.86-1.33; P = .70). Median overall survival was 14.65 (80% CI, 12.39-15.67) months in the ramucirumab plus S-1 and oxaliplatin arm and 14.26 (80% CI, 13.83-17.31) months in the placebo plus S-1 and oxaliplatin arm (HR, 1.11; 80% CI, 0.89-1.40; P = .55). The most commonly reported grade 3 or higher treatment-emergent adverse events in the ramucirumab plus S-1 and oxaliplatin arm in part A were decreased neutrophil count (14 patients [14.6%]), hypertension (10 patients [10.4%]), and anemia (10 patients [10.4%]). In this randomized clinical trial, the addition of ramucirumab to first-line S-1 and oxaliplatin treatment did not prolong progression-free survival or overall survival compared with S-1 and oxaliplatin alone among East Asian patients with advanced gastric cancer; no new safety signals for ramucirumab were identified. ClinicalTrials.gov identifier: NCT02539225.

Abstract 4891: Gene expression analysis of paired baseline (BL) and on-treatment tumor samples from FAIRLANE, a double-blind placebo (PBO)-controlled randomized phase II trial of neoadjuvant ipatasertib (IPAT) plus paclitaxel (PAC) in early triple-negative breast cancer (eTNBC)

Abstract Purpose: In the FAIRLANE trial (NCT02301988) in eTNBC, adding the oral AKT inhibitor IPAT to neoadjuvant PAC led to numerical increases in rates of pathologic complete response (pCR; primary endpoint) and complete response (CR) by MRI in unselected patients (pts), with a numerically greater treatment effect in pts with PIK3CA/AKT1/PTEN-altered tumors [Oliveira et al., AACR 2018]. There was no association between PIK3CA/AKT1/PTEN alterations and response in the PBO arm. Gene expression analysis was performed to evaluate on-treatment changes in the tumor microenvironment and association with response in both treatment arms. Methods: Gene expression at BL and cycle 1 day 8 (C1D8) was evaluated by RNA sequencing using TruSeq RNA Access (Illumina, Inc., San Diego, CA, USA) at Expression Analysis (Morrisville, NC, USA). Paired samples (pts with RNA-seq at both BL and C1D8) were compared to assess on-treatment changes in gene expression. Using RNA-seq data, in silico cell-type enrichment analysis was performed using xCell to calculate the percentage of infiltrating immune cells [Aran et al., Genome Biol 2017]. Results: Paired samples were available from 87 (58%) of the 151 treated pts; response results in this subset were representative of the overall population. Calculated infiltrating immune cell scores (xCell) increased from BL to C1D8 in both treatment arms, exemplified by increases in multiple immune cell biomarkers (eg CD8A, GZMA, CXCL9, CD274/PD-L1). In the PBO arm, higher C1D8 immune score showed a significant association with better response (pCR or response by MRI); the association was stronger for C1D8 than for BL or change from BL immune score. However, there was no association between immune score (BL, C1D8, or change from BL) and response in the IPAT arm. At C1D8, IPAT-treated pts with a CR by MRI had lower average immune scores than PBO-treated pts with a CR. Among the 14 IPAT-treated pts who achieved a CR by MRI, all 7 pts with immune scores below the median had PIK3CA/AKT1/PTEN-altered tumors compared with only 3 of 7 pts with immune scores above the median. Conclusions: This exploratory gene expression analysis revealed differential associations of immune infiltration and tumor response depending on treatment. PAC treatment appears to increase immune cell infiltration in the eTNBC setting, and the presence of a T cell-rich environment (at C1D8) is strongly associated with improved outcomes in pts treated with single-agent PAC. However, the addition of AKT inhibition to PAC is especially effective in pts with PIK3CA/AKT1/PTEN-altered tumors, including those with low immune infiltration. Together, the results hint at multiple mechanisms in killing tumor cells when combining IPAT with PAC. Citation Format: Zhen Shi, Steven J. Isakoff, Cristina Saura, Paolo Nuciforo, Isabel Calvo, Jay Andersen, José Luis Passos Coelho, Miguel Gil Gil, Begoña Bermejo, Debra A. Patt, Eva Ciruelos, Matthew J. Wongchenko, Stina M. Singel, Na Xu, Lorena de la Peña, José Baselga, Steven Gendreau, Mafalda Oliveira. Gene expression analysis of paired baseline (BL) and on-treatment tumor samples from FAIRLANE, a double-blind placebo (PBO)-controlled randomized phase II trial of neoadjuvant ipatasertib (IPAT) plus paclitaxel (PAC) in early triple-negative breast cancer (eTNBC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4891.

Value of adjuvant chemotherapy using paclitaxel plus carboplatin after radical surgery with or without radiotherapy in stage IB-iia cervical adenocarcinoma with risk factors.

e17016 Background: The aim of this study was to evaluate the efficacy and safety of paclitaxel/carboplatin as an adjuvant systemic chemotherapy for stage IB-IIA cervical adenocarcinoma patients after radical hysterectomy and pelvic lymphadenectomy with or without radiotherapy(RT). Methods: The cases of all patients (n = 152) with FIGO IB-IIA cervical adenocarcinoma who were treated by radical hysterectomy and pelvic lymphadenectomy with or without RT at Chinese academy of medical sciences cancer institute and hospital between January 2008 and January 2017 were reviewed. Of these, 35 patients displayed high-risk prognostic factors (high-risk group), 65 displayed intermediate-risk prognostic factors meeting sedlis criteria(intermediate-risk group),and 54 cases presented poorly differentiated status or LVSI, without other risk factors. In the high-risk group,18 patients received adjuvant radiotherapy and concurrent cisplatin chemoradiotherapy(RT-CCRT ) and 17 received adjuvant radiotherapy plus systemic chemotherapy using Paclitaxel Plus Carboplatin (RT-CT ). In the intermediate-risk group, 47 patients were treated with RT-CCRT and 16 were treated with RT-CT ,among the patients with poorly differentiated status or LVSI ,20 were treated with adjuvant chemotherapy using Paclitaxel Plus Carboplatin (CT ) and 34 received no further treatment (NFT). Results: In the high-risk group, adjuvant RT-CT was significantly superior to RT-CCRT with regard to median PFS and 2-year PFS rate(93.07months vs 52,44months, 94.1% vs 72.2%), but the recurrence rate and survival rate showed no significantly difference(11.8% vs 33.3%,100% vs 83.3%) . In the intermediate-risk group, Patients receiving RT-CT showed a better 2-year PFS rate and recurrence rate compared to those with RT-CCRT (100% vs 90.7%, 6.3% vs 12.6%), but the differences were not statistically significant. Among the patients with poorly differentiated status or LVSI, addition of adjuvant systemic chemotherapy resulted in significantly improved 2-year PFS rate compared with the NFT group (95% vs. 75.2%,p = 0.032). Conclusions: Adjuvant systemic chemotherapy using Paclitaxel Plus Carboplatin improved the prognosis of FIGO stage IB-IIA cervical adenocarcinoma patients in the high-risk group and patients who presented 2 or more intermediate-risk factors. Early cervical adenocarcinoma patients with low differentiation or LVSI can also benefit from postoperative adjuvant TC chemotherapy.

Risk Factors for Peripheral Neuropathy Induced by Albumin-bound Paclitaxel Plus Gemcitabine Therapy in Pancreatic Cancer Patients

Risk Factors for Peripheral Neuropathy Induced by Albumin-bound Paclitaxel Plus Gemcitabine Therapy in Pancreatic Cancer Patients

HGCSG 1603: Phase II study of ramucirumab and irinotecan combination therapy as second-line treatment in patients with metastatic or advanced gastric cancer.

TPS183 Background: As second-line chemotherapy for gastric cancer, a survival benefit has been shown in several clinical trials. Irinotecan and taxanes are recommended as second-line regimen. However, therapeutic outcomes have remained unsatisfactory and more effective treatment are expected. Ramucirumab (RAM) is a fully human IgG1 monoclonal vascular endothelial growth factor receptor-2 (VEGFR-2) antibody that prevents ligand binding of VEGF-A, VEGF-C, and VEGF-D and the receptor-mediated pathway activation in endothelial cells, subsequently inhibiting neovascularization. In the REGARD study, RAM monotherapy for previously treated advanced gastric or gastro-esophageal junction adenocarcinoma improved median overall survival (mOS) compared with placebo. Moreover, in the RAINBOW study, RAM plus paclitaxel (PTX) versus placebo plus PTX, mOS showed significantly longer in RAM plus PTX group than in placebo plus PTX group. In contrast, there are no data on the efficacy of RAM and irinotecan in the second-line treatment for gastric cancer. The WJOG 4007 study demonstrated an equivalent efficacy between irinotecan and PTX. In this study, we propose to examine the efficacy of RAM plus irinotecan. Methods: This study is carried out as a multicenter, non-randomized, single arm, prospective, phase II study. The patients with metastatic or advanced gastric cancer that is refractory or intolerance to primary chemotherapy are eligible for this study. RAM and irinotecan combination therapy is administered every two weeks, which is continued until progression or emergence of adverse events requiring discontinuation. The primary endpoint is progression-free survival rate at six months, and the secondary endpoints are OS, progression-free survival, response rate, safety, and dose intensity for each drug. A total of 35 cases areplanned for registration. This study is registered with the University Hospital Medical Information Network. Clinical trial information: UMIN000030372.

Association between Paclitaxel Clearance and Tumor Response in Patients with Esophageal Cancer.

Inter-individual variability in paclitaxel pharmacokinetics may play a role in the response to chemotherapy. Therefore, we studied the association between paclitaxel clearance and treatment response in patients with esophageal cancer. All patients who received paclitaxel (plus carboplatin) treatment for esophageal cancer between 2007 and 2013 were included. The treatment was given as neoadjuvant chemoradiotherapy (nCRT), induction chemotherapy (iCT), or palliative chemotherapy (pCT). The treatment response was assessed by the tumor regression grade (TRG) or by the RECIST1.1 criteria, respectively. The unbound paclitaxel clearance (CL) was estimated with NONMEM. The log-transformed clearance was related to response with ANOVA and independent sample t-tests. A total of 166 patients were included, of whom 113 received nCRT, 23 iCT and 30 pCT. In patients receiving nCRT, paclitaxel clearance was not associated with tumor regression grade (p-value = 0.25), nor with pathologically complete response (geometric mean 561.6 L/h) and residual disease (geometric mean 566.1 L/h, p-value = 0.90). In patients who underwent iCT or pCT, also no association between paclitaxel clearance and RECIST outcome was identified (iCT: p-value = 0.08 and pCT: p-value = 0.81, respectively). In conclusion, systemic paclitaxel exposure was not associated with response to common paclitaxel-based treatment regimens for esophageal cancer. Future studies should focus on tumor exposure in relation to systemic exposure and treatment outcome.

Clinical usefulness of ramucirumab plus paclitaxel for unresectable and recurrent gastric cancer.

Introduction Recently in Japan, Ramucirumab (RAM) became the first anti-angiogenic agent to be approved for second-line treatment of gastric cancer. In the present study, we aimed to evaluate the efficacy and safety of RAM plus paclitaxel (PTX) in patients with unresectable and recurrent gastric cancer in our institution.Patients and Methods The subjects were 11 patients with unresectable and recurrent gastric cancer who received RAM plus PTX as a second- or later-line treatment at our hospital between June 2015 and September 2017, after the failure of previously-attempted treatments. We assessed the efficacy and safety of RAM plus PTX, and also compared them between patients aged <75 years (n=6) and those aged ≥75 (n=5), by performing a retrospective analysis based on the data obtained from daily clinical practice for gastric cancer treatment.Results Objective tumor response was observed in one of the 11 patients (9.1%) with partial response, and disease control was seen in the remaining 10 (90.9%). The median overall survival (OS) and progression-free survival (PFS) of the patients were 20.8 months (95% CI 7.8-NA (not applicable)) and 11.3 months (95% CI 6.5-NA), respectively. There were no serious adverse events. The median OS for the <75 years group and ≥75 years group was NA (due to short follow-up period) and 20.8 months (p = 0.336), respectively, and their respective median PFS rates were 9.4 and 11.3 months (p = 0.492). The difference of rate of adverse events was not significant between the two age groups in the present study, though the number of adverse events was not sufficient.Conclusion The results of the present study suggest that the combination chemotherapy of RAM and PTX was effective in unresectable and recurrent gastric cancer patients as a second- or later-line therapy, and has been shown to be safe and feasible in elderly patients.

169P - Apatinib reverses resistance of paclitaxel-containing regimens in advanced gastric cancer: A phase II study

Background: In the previous observational study, apatinib plus paclitaxel (PTX)-based regimens showed a progression-free survival (PFS) benefit of 4.1 months in 7 gastric cancer patients (pts) resistant to PTX-contained chemotherapy (ASCO-GI 2017, abstr. 89). Hence, we conducted a single-arm phase II clinical trial (Ahead-G323) to confirm apatinib in reversing resistance of PTX-containing regimens. The intermediate analysis has been reported in ASCO 2018 (abstr. e16055). Herein, we further released the updated data. Methods: Advanced or metastatic gastric cancer pts with measurable lesions resistant to PTX-containing regimens (disease progression during or within 3 months after chemotherapy) were recruited. According to ECOG performance status (PS) and drug resistance profile, pts received apatinib (850 mg or 750 mg, po, qd) combined with PTX alone (80 mg/m2, d1, d8, and d15; q4w), POF (PTX 135 mg/m2, oxaliplatin 85 mg/m2, and leucovorin 400 mg/m2, d1; 5-FU 2400 mg/m2 for 46 h; q2w) or other PTX-containing regimen. Results: As of 6/21/2018, all 20 preplanned pts were enrolled. The baseline characteristics are shown in the table. Seventeen pts were available for response evaluation: 5 got partial response, 9 had stable disease, and 3 had progressive disease, resulting in an overall response rate of 29.4% and a disease control rate of 82.4%%, at best response. The median PFS was 4.2 (95%CI, 2.0–6.8) months. The 6-month PFS was 34.6% (95%CI, 9.7%–59.5%). Pts were still in follow-up. Moreover, the most common adverse events (AEs) were neutropenia (80.0%), leukopenia (75.0%), and hypoproteinemia (65.0%). The most common grade 3/4 AEs include neutropenia (30.0%), leukopenia (30.0%), and hypertensionTable169P Baseline characteristicsCharacteristicsN (%)Total20Age, yearsMedian (range)54.50 (45.5, 61.0)GenderFemale8 (40.0%)ECOG PS05 (25.0%)115 (75.0%)Metastatic lesion≤212 (60.0%)>28 (40.0%)Prior chemotherapy, lines17 (35.0%)28 (40.0%)35 (25.0%) Open table in a new tab (30.0%). Conclusions: This study demonstrated that apatinib combined with PTX-containing regimen could bring benefit on responses and survival for advanced or metastatic gastric cancer pts resistant to PTX-containing regimen. Clinical trial identification: NCT02697838, March 3, 2016. Legal entity responsible for the study: Fujian Cancer Hospital. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

P3.01-15 Efficacy of Paclitaxel Plus TS1 Against Non-Small Cell Lung Cancer Previously Treated

Salvage chemotherapy is frequently used. However, the efficacy of salvage chemotherapy of paclitaxel plus TS1 (TTS1) is still unknown. We retrospectively reviewed the chart records of our non-small cell lung cancer patients who were treated between 2010 and 2013. Clinical characteristics, type of tumor EGFR mutation, response to first-line EGFR-TKI treatment or not, and efficacies of TTS1, were collected. Total 25 patients were enrolled in this study. No patients archived complete response and six patients had partial response (ORR: 24%). The disease control rate was 60% (15/25). The progression free survival (PFS) was 4.8 months and overall survival (OS) was 12.4 months. Among these 25 patients that received TTS1, 17 of them had driver mutations. Patients with driver mutations had better PFS (4.9 months vs 1.8 months) and OS (15.5 months vs 7.2 months) compared with those without driver mutations. TTS1 are effective salvage chemotherapeutic agents, especially in tumor EGFR mutated patients. Paclitaxel plus TS1 is another treatment of choice for NSCLC patients before a more efficient salvage treatment strategy is found.

Paclitaxel Plus Cetuximab as 1st Line Chemotherapy in Platinum-Based Chemoradiotherapy-Refractory Patients With Squamous Cell Carcinoma of the Head and Neck.

Purpose: We sought to evaluate the efficacy and safety of the combination of cetuximab (Cmab) and paclitaxel (PTX) in patients with squamous cell carcinoma of the head and neck (SCCHN) who had unresectable recurrent or metastatic (R/M) disease after platinum-based chemoradiotherapy.Materials and Methods: Data on 23 patients with SCCHN who received paclitaxel and cetuximab (Cmab) for R/M disease no more than 6 months after CRT completion were retrospectively reviewed. PTX and Cmab were given in a 28-day cycle (PTX, 80 mg/m2 on days 1, 8, and 15; Cmab, loading dose 400 mg/m2 followed by a weekly 250 mg/m2). The differences in prognosis between subgroups in different clinical settings were also assessed.Results: CRT had been delivered as definitive treatment in 13 cases (57%) and as adjuvant treatment in 10 (43%). Median time from CRT completion to disease recurrence or metastasis was 73 days (1–152). The best objective response and disease control rates were 52 and 83%, respectively, with 12 partial responses and seven cases of stable disease by Response Evaluation Criteria in Solid Tumors (RECIST). A total of 17 of 23 patients (74%) achieved a degree of tumor shrinkage. Median progression-free survival (PFS) and overall survival (OS) were 7.0 (95% confidence interval [CI]: 3.7–8.4) and 16.3 months (95% CI: 7.8–23.3), respectively. Patients with a longer duration (≥60 d) from CRT completion to disease progression had a statistically significantly longer OS than the others (median OS 22.3 vs. 8.1 months, log-rank test; p = 0.034). Main Grade 3 toxicities included neutropenia (13%), anemia (13%), and hypomagnesemia (13%). No Grade 4 toxicity or treatment-related death was seen.Conclusion: PTX and Cmab is a tolerable and effective option in SCCHN patients with symptomatic CRT-refractory disease. Its favorable effects on tumor shrinkage will help relieve tumor-associated symptoms.

The BRIGHTER trial: A phase 3 randomized double-blind study of napabucasin (NAPA) plus paclitaxel (PTX) versus placebo (PBO) plus PTX in patients (pts) with pretreated advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma.

4010Background: NAPA is an oral investigational agent, hypothesized to inhibit cancer stemness pathways, including STAT3 pathway implicated in cancer stem-cell viability. Synergistic antitumor acti...

Survival benefit of patients with early-stage ovarian carcinoma treated with paclitaxel chemotherapeutic regimens.

ObjectiveAdjuvant chemotherapy was introduced in patients with early-stage ovarian cancer (OC). The benefit of standard chemotherapeutic regimens including taxane has not been established.MethodsPatients with early-stage OC from the National Health Insurance Research database of Taiwan who received platinum plus cyclophosphamide (CP) or platinum plus paclitaxel (PT) for 3–6 cycles were recruited, and the disease-free survival (DFS) and overall survival (OS) were determined.ResultsA total of 1,510 early-stage OC patients, including 841 who received CP regimen and 699 who received PT regimen, were included. The 2 groups had a similar estimated probability of 5-year DFS (PT vs. CP, 79.0% vs. 77.6%; p=0.410) and OS (84.6% vs. 84.3%; p=0.691). Patients >50 years of age who received the CP regimen had a lower 5-year DFS than the patients ≤50 years of age who received the CP (p<0.001) or PT regimens (p=0.001). Additionally, patients >50 years of age who received the CP regimen had a worse 5-year OS compared with the other 3 groups (p=0.019) (p=0.179 for patients >50 years of age in the PT group; p=0.002 for patients ≤50 years of age in the CP group; and p=0.061 for patients ≤50 years of age in the PT group). Patients with the CP or PT regimen for 3–5 cycles had a similar 5-year DFS and OS compared to 6 cycles (p>0.050).ConclusionChemotherapeutic regimens with taxane could be recommended for early-stage OC patients >50 years of age.

Concurrent chemoradiotherapy with paclitaxel and cisplatin for patients of locally advanced cervical squamous cell carcinoma: A single-arm phase II clinical study

Objectives: A phase II study was conducted to investigate the safety and efficacy of a regimen of cisplatin (DDP) plus paclitaxel (PTX) concurrent with radiotherapy (RT) in patients with locally advanced cervical squamous cell carcinoma (LACSC). Patients and Methods: 34 patients with newly diagnosed LACSC confirmed by histopathology, with a Karnofsky performance status ≥ 60, no prior cervical cancer treatment, and no chemotherapy contraindications were enrolled. Concurrent chemoradiotherapy (CCRT) was delivered to all cases. The chemotherapy consisted of two 3-week cycles of DDP (30 mg/m2/d) for 3 d plus PTX (135 mg/m2) for 1 d. Concurrent radiation (pelvic irradiation of 45 Gy/25 Fx (PTV); lesion boost of 5-10 Gy (GTV); total dose 70-80 Gy) was administered by 3-dimensional conformal radiotherapy (3DCRT; N=14) or intensitymodulated radiation therapy (IMRT; N=20). Short-term efficacy and 1, 2 and 3 y, overall survival (OS) rates, and adverse reactions were analyzed. Results: The cohort of 34 patients (median age, 60 y; range, 35-74) included 4 stage Ib2 cases, 16 stage II cases, 10 stage III cases, and 4 stage IV cases. With a median follow-up period of 38 months, the overall response rate (ORR) was 28/34 (82.4%), including a 12 (35.3%) with a complete response (CR) rate and 16 (47.1%) with a partial response (PR). The 1, 2 and 3 y OS rates were 100%, 94.1%, and 88.2%, respectively. Grade III occurred in 12 patients (35.3%), but no patients suffered from grade IV myelosuppression. Gastrointestinal tract reactions, vaginitis, proctitis, and cystitis were common by mild in all cases. Conclusion: CCRT with DDP plus PTX produced an encouraging and OS rates and ORR with relatively tolerable hematological toxicity.

P1-347 - Actual clinical use of Ramucirumab plus Paclitaxel at our hospital

In Japan, use of ramucirumab (RAM) to gastric cancer approved for manufacture and marketing in March 2015. We decided to verify the results of actual clinical use. Besides, since treatment regimens for S-1 refractory relapse gastric cancer have not been determined, these patients at our hospital were also examined. We retrospectively analyzed gastric cancer patients who received RAM plus paclitaxel (PTX) between March 2015 and December 2016 at the The Japanese Red Cross Nagasaki Genbaku Hospital. Patients received RAM 8 mg/kg intravenously on days 1 and 15, plus PTX 80 mg/m2 intravenously on days 1, 8, and 15 of a 28-day cycle. The overall response rate (RR) by Response Evaluation Criteria in Solid Tumors guidelines version 1.1 and progression-free survival (PFS) were evaluated. In addition, the same analysis was conducted for S-1 refractory relapse gastric cancer at our hospital. Fourteen patients received RAM plus PTX. The RR for 8 assessable patients was 37.5% (95% Confidence Interval (CI), 8.5-75.5), the median PFS was 5.2 months, and the RR for 4 assessable patients was 50% (95% CI, 6.8-93.2), the median PFS was 5.0 months in S-1 refractory relapse gastric cancer patients who received RAM plus PTX as 2nd line. The results of actual clinical use of RAM plus PTX at our hospital were also the same as previously reported in RAINBOW trial. Further prospective evaluations for S-1 refractory relapse gastric cancer are warranted.

Sequential Therapy of Breast Cancer Cell Lines with Vitamin C and Quercetin Improves the Efficacy of Chemotherapeutic Drugs

ABSTRACTObjective: Prevention by antioxidant agents including vitamin C (VC) and quercetin (QU), which are nontoxic, cost effective, and physiologically bioavailable, is a promising approach in breast cancer handling. The aim of this work is to investigate the influence of VC+QU on cytotoxicity profile of doxorubicin (DOX) plus paclitaxel (PAC) in breast cancer cells. Methods: The effect of each drug on its own or in combination was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Combination indexes were calculated using the Chou–Talalay method. Apoptosis and cell cycle analysis was investigated by flow cytometric assays. Results: Combination treatment with VC+QU plus drugs diminished IC50 value 2.28–7.7 and 10.5–66.6 fold in comparison with the drugs and PAC treatment alone, respectively, in all breast cancer cells and induced apoptosis at the early stages more than the treatment with the drugs alone (P<0.01). A marked reduction in Go/G1 and S phases was reported after combination therapy in MDA-MB 231 and MDA-MB 468 cells. MCF-7 cells demonstrated lower fractions of cells in S phase with no significant changes in G2/M phase (P < 0.01). The same treatment produced a significant increase in S and G2/M phases in A549 cells (P < 0.001). Conclusion: Our results emphasized the importance of VC+QU in combination with the drugs to produce a synergistic antitumor effect in breast cancer cells.

Abstract AP30: PHASE IB/II WITH EXPANSION OF PATIENTS AT THE MTD STUDY OF OLAPARIB PLUS WEEKLY (METRONOMIC) CARBOPLATIN AND PACLITAXEL IN RELAPSED OVARIAN CANCER PATIENTS

Abstract BACKGROUND: We established the olaparib tablet maximum tolerated dose (MTD) at 150 mg bid, dose limiting toxicities (DLT's) and response to therapy or carboplatin, paclitaxel and olaparib tablet given simultaneously, reported at ASCO 2014. This abstract will include data from both the phase 1b and the phase 2 expansion. METHODS: A total of 54 subjects were evaluated in this trial, 14 in phase 1b and 40 in phase 2. Eligibility required measurable disease, adequate organ function and ECOG performance status of ~ 2. Subjects had to have failed first line platinum containing chemotherapy. BRCA testing was conducted as available. Subjects received the metronomic therapy of paclitaxel 60mg/m2 IV and carboplatin AUC 2 IV weekly, 3 weeks out of 4, and olaparib tablets at 150 mg bid administered orally for 3 consecutive days (D1-D3) every week for each cycle. Subjects were assessed for toxicity and response according to the protocol. Subjects that reached a confirmed complete remission were transitioned to olaparib tablets only, 300 mg bid until disease progression. RESULTS: Median age was 58 and median number of prior regimens was 4. There have been no deaths due to the study regimen. One patient had grade 4 neutropenia and an allergic reaction to carboplatin. The common grade 3/4 toxicities were caused by the chemotherapy (neutropenia. anemia and thrombocytopenia). Two patients had mild GI toxicities. One patient had a skin rash. There was no evidence of cardiac, hepatic, or pulmonary toxicities in any of these patients. 25% of subjects had a complete remission (CR), 31% had PR, 23% had SD and 21% had PD. Of the 13 CRs, 4 were BRCA negative. PFS median for BRCA positive subjects is 12.6 months vs 4.8 months for BRCA negative subjects. OS median for BRCA positive subjects is 24 months vs 16 months for BRCA negative subjects. All of the CR's are alive. CONCLUSION: Olaparib tablet can be safely administered simultaneously with a weekly regimen of carboplatin and paclitaxel in heavily pretreated ovarian cancer patients. Olaparib appears to be highly effective in BRCA positive subjects. This is the first successful combination of olaparib tablets with carboplatin and paclitaxel that has been well tolerated. Citation Format: Rivkin SE, Moon J, Iriarte D, Sloan H, Wiseman C, Klee M, Ference K, Drescher C, Veljovich D, Bondurant A, Peters W, Jiang P, Goodman G, Park M, Fer M, Shah C, Johnston E, Kaplan H, Wahl T, Ellis E. PHASE IB/II WITH EXPANSION OF PATIENTS AT THE MTD STUDY OF OLAPARIB PLUS WEEKLY (METRONOMIC) CARBOPLATIN AND PACLITAXEL IN RELAPSED OVARIAN CANCER PATIENTS [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr AP30.

Sa1273 - Ratio of Neutrophil to Lymphocytes is Useful to Predict the Prognosis of Patients with Paclitaxel Plus Ramucirumab Treatment for Unresectable Advanced Gastric Cancer

Sa1273 - Ratio of Neutrophil to Lymphocytes is Useful to Predict the Prognosis of Patients with Paclitaxel Plus Ramucirumab Treatment for Unresectable Advanced Gastric Cancer

Cisplatin and paclitaxel co-delivered by folate-decorated lipid carriers for the treatment of head and neck cancer

Context: For head and neck cancer therapy, co-delivery of two drugs, cisplatin (DDP) plus paclitaxel (PTX), are more effective than single drug therapy. Lipid carriers are promising drug carriers for anti-cancer delivery.Objective: The aim of this study is to construct a folate (FA) decorated nanostructured lipid carriers (NLCs) as nanocarriers for DDP and PTX delivery.Materials and methods: In this study, DDP and PTX were incorporated into NLCs. Folate-PEG-DSPE (FA-PEG-DSPE) was synthesized and decorated the drugs-loaded NLCs (FA-DDP/PTX NLCs). Their average size, zeta potential, drug encapsulation efficiency, drug loading capacity, and in vitro drug release were evaluated. Head and neck cancer cells (FaDu cells) were used for the testing of in vitro cytotoxicity, and in vivo transfection efficiency of NLC was evaluated on mice bearing FaDu cells model.Results: The size of FA-DDP/PTX NLCs was around 127 nm, with a positive zeta potential of 26.7 mV. FA-DDP/PTX NLCs showed the highest cytotoxicity and synergistic effect of two drugs in head and neck cancer cells (FaDu cells) in vitro. The in vivo study revealed the greatest anti-tumor activity than all the other formulations in murine-bearing head and neck cancer model.Discussion and conclusion: FA-DDP/PTX NLCs effectively improves anticancer efficiency for head and neck cancer in vitro and in vivo. The constructed NLCs could be used as a novel carrier to co-delivery DDP and PTX for head and neck cancer therapy.

MTE17.02 Maintenance Therapy versus Early Second-Line Therapy in Advanced NSCLC

MTE17.02 Maintenance Therapy versus Early Second-Line Therapy in Advanced NSCLC