Paclitaxel Regimen Research Articles

A phase II study of concurrent chemoradiotherapy combined with a weekly paclitaxel and 5-fluorouracil regimen to treat patients with advanced oesophageal carcinoma

BackgroundA phase II study was performed to investigate the safety and efficacy of weekly doses of combined paclitaxel and 5-fluorouracil (5-FU) with concurrent radiation therapy, followed by 2 cycles of consolidation chemotherapy to treat patients with advanced oesophageal carcinoma.MethodsThe eligibility criteria included local, advanced, newly diagnosed and postoperative local regional lymph node metastasis; an Eastern Cooperative Oncology Group (ECOG) score of ≤ 2; and adequate organ function. Patients received chemoradiotherapy consisting of radiotherapy (50.4 Gy/28 Fx or 61.2 Gy/34 Fx) and concurrent paclitaxel (50 mg/m2) and 5-FU (300 mg/m2) for 96 h on days 1, 8, 15, 22, and 29. The two-cycle consolidation chemotherapy protocol included paclitaxel (175 mg/m2) plus continuously infused 5-FU (1800 mg/m2) for 72 h administered on days 57 and 85, after concurrent chemoradiotherapy.ResultsBetween February 2012 and August 2013, 53 patients with oesophageal carcinoma were enrolled in the study. Among these patients, 33 (62.2%) were newly diagnosed and 20 (37.7%) had postoperative local regional lymph node metastasis. The median overall survival (OS) time was 17.9 months (95% CIs = 11.9-23.9), and the median progression-free survival (PFS) time was 12.4 months (95% CIs = 8.6-16.1). Approximately 84.9% (45/53) and 50.9% (27/53) of the patients completed ≥ 5 cycles and all 7 cycles of chemotherapy, respectively. Approximately 86.7% (46/53) of patients completed radiation therapy. The 1-, 2-, and 3-year OS rates were 66.0%, 37.7%, and 35.8%, respectively. The 1-, 2-, and 3-year local control rates were 76.9%, 66.4%, and 66.4%, respectively. Seventeen patients (32%) experienced grade 3 or higher toxicity. Grade 3 to 5 toxicity during chemoradiotherapy included neutropaenia (7.5%), thrombocytopaenia (1.8%), fatigue (7.5%), anaemia (1.8%), dermatitis radiation (1.8%), pneumonitis (5.6%), oesophagitis (9.4%) and vomiting (3.7%).ConclusionsThe combination of weekly doses of paclitaxel and 5-FU was well tolerated and produced comparable results among patients with locally advanced oesophageal cancer. A randomised phase III trial (NCT01591135) comparing paclitaxel plus 5-FU with cisplatin plus 5-FU is on-going at our hospital.

Chemoradiation Including Paclitaxel for Locally Recurrent Muscle-invasive Bladder Cancer in Elderly Patients.

To evaluate outcomes and toxicities of chemoradiation with a less intensive paclitaxel regimen for locally recurrent bladder cancer. Three elderly patients received simultaneous chemoradiation for recurrent muscle-invasive bladder cancer. Chemotherapy included two courses (three times 25 mg/m2 over 1.5 weeks) of paclitaxel. Radiotherapy doses were 59.4 Gy to the bladder and 50.4 Gy to regional lymph nodes. Survival, local control and toxicities were retrospectively evaluated. One patient died after 71 months, two were alive after 69 and 98 months, respectively. No local recurrence was not observed. Five-year survival and local control rates were 100%. Two patients experienced grade 1 acute dysuria, one patient grade 1 diarrhea. Late toxicities were also mild; two patients had grade 1 dysuria. Chemoradiation with a less intensive paclitaxel regimen resulted in excellent 5-year results and was very well tolerated. It may be a reasonable option for elderly patients who cannot tolerate more intensive approaches.

Dual HER2-blockade with pertuzumab and trastuzumab in HER2-positive early breast cancer: a subanalysis of data from the randomized phase III GeparSepto trial

The neoadjuvant phase III GeparSepto study showed that substituting nab-paclitaxel for standard solvent-based paclitaxel significantly improved the pathologic complete response (pCR) rate achieved with a sequential neoadjuvant chemotherapy regimen of paclitaxel, epirubicin, and cyclophosphamide for high-risk primary breast cancer. Recent trials demonstrated that in HER2+ breast cancer pCR can be increased by using pertuzumab in addition to trastuzumab and chemotherapy. The present analysis focuses on efficacy and safety data from the subset of patients with HER2+ tumors from the GeparSepto trial (n = 396) in comparison to the HER2- cohort. Patients with histologically confirmed breast cancer (n = 1206) received four cycles of weekly paclitaxel [either solvent-based (Pac) or nab-paclitaxel (nab-Pac), according to randomization] followed by 4 cycles of epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 q3w, with concurrent trastuzumab and pertuzumab q3w for those with HER2+ tumors. The primary endpoint was pCR defined as ypT0 ypN0. Higher rates of pCR were achieved in HER2+ than in HER2- tumors (57.8% versus 22.0%, P < 0.0001), with the highest rate in the HER2+/HR- cohort (71.0%; 66.7% Pac, 74.6% nab-Pac). In HER2+/HR+ tumors, the pCR rate was 52.9% (49.7% Pac, 56.4% nab-Pac). Grade ≥3 toxic effects were significantly more common in HER2+ than in HER2- patients, with grade 3-4 diarrhea in 7.6% versus 0.9% (P < 0.001) and febrile neutropenia in 6.3% versus 3.3% (P = 0.023) of patients. Left ventricular ejection fraction decreases from baseline were uncommon, with 2.0% versus 0.4% of patients showing decreases to <50% along with a ≥10% decrease from baseline. In HER2+ early breast cancer, a dual HER2-targeted combination of pertuzumab and trastuzumab, together with taxane-epirubicin-cyclophosphamide neoadjuvant chemotherapy, achieved high rates of pCR.

Abstract P4-22-21: NCI9782: A phase 1 study of talazoparib in combination with carboplatin and paclitaxel in patients with advanced solid tumors

Abstract Background: Poly(ADP-ribose) polymerase (PARP) enzymes are involved in DNA repair and activated by DNA strand breaks. DNA damage from carboplatin is associated with activation of PARP. Preclinical data indicate that PARP inhibition potentiates the anti-tumor effect of platinum chemotherapy. Talazoparib (T) is an oral, selective PARP inhibitor with a single agent maximum tolerated dose (MTD) of 1mg orally qd. Primary dose-limiting toxicity (DLT) was thrombocytopenia. This phase I study combines T with the commonly used chemotherapy regimen of carboplatin (C) and paclitaxel (P). Methods: Two dosing schedules are being investigated. In both schedules, C is administered on day 1 and P on days 1, 8, and 15 of a 21-day cycle. T (100-1000mcg) is dosed once daily for days 1-7 (schedule A) or days 1-3 (schedule B) starting on day 1. A 3+3 design is used for dose escalation. Key eligibility criteria include age 318 with a measurable or evaluable solid incurable malignancy. Patients (pts) must have tumor type that is expected to respond to C + P or have BRCA germline or somatic mutation. Stable, treated brain metastases are allowed. No prior C for metastatic disease is allowed. Pts must have platelets&amp;gt;150 and no need for anticoagulation. After 4-6 cycles of combination therapy, pts may continue the combination, change to C and intermittent T without P or change to T alone with continuous daily dosing. Each schedule will have a 6 subject dose expansion at the MTD. The starting dose level for schedule B will be the MTD from schedule A. Results: Schedule A cohort results are reported: 11 pts (median age 59 [range 39-68]; 8 female; 3 male) have been enrolled. Pts had breast (6), ovarian (2), pancreatic (1), and SCC of oropharynx (1) and concurrent ovarian and pancreatic (1). Five pts are BRCA2+ and 3 pts are BRCA1+. Dose level 3 on schedule A (T 350mcg with C AUC 6 and P 80mg/m2) exceeded the MTD with 2 of 3 pts experiencing hematologic dose limiting toxicities (DLTs) including 1 pt with grade (gr) 3 neutropenic fever and gr 4 thrombocytopenia and another pt with grade 3/4 neutropenia lasting &amp;gt; 7 days. Most common AEs include neutropenia (grade 3-4: 7), anemia (grade 3-4: 3), and thrombocytopenia (grade 3-4: 4). Results from expansion of dose level 2 (T 250mcg with C AUC 6 and T 80mg/m2) will be presented. The 11 pts were on study a median of 9 weeks (range 9-36+). Four pts have discontinued study therapy: 1 due to need for anticoagulation for PE, 1 for prolonged cytopenias, and 2 for disease progression. Of the 8 pts with measurable disease evaluated for response to date, 4 had SD, 1 had a cPR, 1 had radiographic CR, and 2 with PD. A pt with BRCA 1+ triple negative breast cancer has maintained a prolonged PR (36+ weeks) even after dose reductions to T 100mcg with C AUC 3. One pt with ovarian cancer (BRCA WT) has radiographic CR (CA 125 remains mildly elevated) after 15+ weeks of therapy. Conclusion: PARP inhibition with talazoparib days 1-7 in combination with carboplatin and paclitaxel leads to DLT of myelosuppression. However, clinical responses are seen even with lower dose combinations. Citation Format: Turk A, Chan N, Leal T, O'Regan R, Tevaarwerk A, Rice L, Campbell T, Barroilhet L, Mehnert J, Eickhoff J, Kolesar J, Liu G, Wisinski K. NCI9782: A phase 1 study of talazoparib in combination with carboplatin and paclitaxel in patients with advanced solid tumors [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-22-21.

Abstract OT1-01-09: Feasibility and safety of avoiding granulocyte colony-stimulating factor prophylaxis during the paclitaxel portion of dose dense doxorubicin-cyclophosphamide and paclitaxel regimen

Abstract Background: The need for granulocyte-colony stimulating factor (G-CSF) support during dose-dense (DD) paclitaxel (T) after doxorubicin and cyclophosphamide (AC) is unclear. Given that G-CSF is not devoid of adverse effects, and adds significant costs to treatment, we are examining the feasibility and safety of avoiding G-CSF during dose dense T. Methods: This is a single center, single-arm, phase II, two stage study. The primary aim is to evaluate the rate of T treatment completion within 7 weeks (from D1 of cycle 1 to D1 of cycle 4 of T) omitting Pegfilgrastim using pre-specified safety rules. Secondary aims include: characterization of the utilization of Pegfilgrastim using pre-specified safety rules in patients receiving dose dense T; evaluation of the safety of omitting routine Pegfilgrastim support in patients receiving dose dense T; evaluation of total cost ($ United States) of omitting routine Pegfilgrastim use during dose dense T. As a secondary aim we will evaluate the safety of simplifying the pre-medication regimen used for the T portion of the regimen (withholding corticosteroids in cycle 3 and 4 if no evidence of allergic reactions in cycle 1 and 2). A Simon Optimal design was selected with an overall one-side type I error of 10% and 90% power to detect the difference between unacceptable T completion rate (75%) and desirable completion rate (85%). In the first stage, 51 evaluable patients will be enrolled. If during the first stage, at any point, a total of 12 or more patients do not complete treatment within 7 weeks the trial will be closed permanently. Among the 51 patients enrolled after the first stage, if at least 40 patients complete treatment without dose delay, accrual will continue to the second stage where an additional 74 evaluable patients will be enrolled. If there are at least 100 among the 125 evaluable patients completing treatment without dose delay, the regimen will be considered worthy of further study. If during the second stage, at any point, a total of 26 patients do not complete treatment within 7 weeks the trial will be closed permanently and the study intervention will not be of clinical interest. If the true treatment completion rate is 75%, the chance the regimen is declared ineffective is 91% (exact alpha = 0.094) and if the true treatment completion rate is 85% the chance that the regimen is falsely declared ineffective is 10% (exact power = 0.899). The estimated accrual rate is 6-8 patients/month. Accrual started in April 2016. Clinical trial information: NCT02698891. Citation Format: Barroso-Sousa R, Vaz-Luis I, Guo H, Barry WT, Brackett AM, Brock VA, Roche KA, Kasparian E, Winer EP, Lin NU. Feasibility and safety of avoiding granulocyte colony-stimulating factor prophylaxis during the paclitaxel portion of dose dense doxorubicin-cyclophosphamide and paclitaxel regimen [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-01-09.

Abstract OT2-01-02: COLET: A multistage, phase 2 study evaluating the safety and efficacy of a doublet regimen of cobimetinib (C) in combination with paclitaxel (P) or triplet regimens of C in combination with atezolizumab (atezo) plus either P or nab-paclitaxel (nab-P) in metastatic triple-negative breast cancer (TNBC)

Abstract Preclinical data suggest that upregulation of the MAPK pathway confers resistance to taxane chemotherapy. Mutations and gene amplifications in the MAPK pathway are present in many TNBC tumors and may contribute to taxane resistance. Preliminary data from an initial safety run-in stage of the COLET study (ClinicalTrials.gov ID, NCT02322814; EudraCT number, 2014-002230-32) suggest improvement of clinical outcomes when MEK inhibition is combined with taxane chemotherapy. Additionally, in preclinical models, MEK inhibition was shown to enhance anti–PD-L1 activity. The monoclonal antibody PD-L1 inhibitor atezo has shown promising activity in combination with nab-P in metastatic TNBC. Accordingly, the COLET protocol was amended to include the evaluation of triplet regimens combining atezo with MEK inhibition and taxane chemotherapy[SL1] . COLET is evaluating the safety and efficacy of various combinations of C as first-line treatment for metastatic or locally advanced TNBC. Key eligibility criteria include measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) and left ventricular ejection fraction &amp;gt; institutional lower limit of normal or &amp;gt;50%. Neoadjuvant or adjuvant therapy is allowed if completed &amp;gt;6 months prior to study entry. COLET has 3 cohorts: I, II, and III. Cohort I has 2 stages: an initial safety run-in stage (n∼12) followed by an expansion stage (n∼90) of 1:1 randomization to C + P or placebo (PBO) + P. Patients received P 80 mg/m2 on days 1, 8, and 15 and C/PBO 60 mg/day on days 3-23 of each 28-day cycle. In the expansion stage of Cohort I, randomization is stratified by prior neoadjuvant/adjuvant taxane therapy and disease-free interval from last chemotherapy dose. Cohorts II and III will evaluate the safety and efficacy of adding atezo to C + P or nab-P, respectively. Each cohort has a safety run-in stage (n∼15) and an expansion stage (additional n∼15); each will receive atezo 840 mg on days 1 and 15 and C 60 mg/day on days 3-23 of every 28-day cycle. Cohort II will receive P 80 mg/m2 and Cohort III will receive intravenous nab-P 100 mg/m2 on days 1, 8, and 15. Patients will receive treatment until disease progression or toxicity. The primary efficacy end point is investigator-assessed progression-free survival (PFS) for the expansion stage (Cohort I), and the primary PFS analysis will be performed when 60 PFS events occur across the 2 arms. This provides 77% power to detect a hazard ratio of 0.5 at a two-sided significance level of 0.05. For Cohorts II and III, the primary efficacy end point is overall response rate per RECIST v1.1; secondary end points include duration of response, PFS, and overall survival. Recruitment into the safety run-in stage of Cohort I is complete. Accrual into the randomization stage of Cohort I and the initial safety run-in stage of Cohorts II and III are ongoing. Patients from sites across North America, Europe, and the Asia-Pacific region will be enrolled. Citation Format: Miles D, Kim S-B, McNally V, Simmons B, Wongchenko M, Xu N, Brufsky A. COLET: A multistage, phase 2 study evaluating the safety and efficacy of a doublet regimen of cobimetinib (C) in combination with paclitaxel (P) or triplet regimens of C in combination with atezolizumab (atezo) plus either P or nab-paclitaxel (nab-P) in metastatic triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT2-01-02.

Abstract P2-11-10: Effect of supplementation with eicosapentaenoic and docosahexaenoic omega-3 polyunsaturated fatty acid on the chemotoxicity in Mexican patients with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy (NeoCT)

Abstract The aim of this study was to determine the benefits of supplementation with eicosapentaenoic (EPA) and docosahexaenoic (DHA) polyunsaturated fatty acids (PUFA) in terms of chemotoxicity and inflammatory status, to Mexican women with locally advanced breast cancer (LABC), receiving a standard neoadjuvant chemotherapy (NeoCT AC-taxol regimen). We performed a randomized double-blind, placebo-controlled, clinical trial, in which we studied 44 LABC patients (stages IIA to IIIA) who took 2.4g/d (1.6 g EPA and 0.8 g DHA, ratio 2:1) (N=22) or placebo (N=22) during NeoCT with doxorubicin/ cyclophosphamide followed paclitaxel weekly. Edmonton Scale and Common Terminology Criteria for Adverse Events (CTCAE) v4. assessment were performed before each CT, and also blood total leukocytes, and percentage lymphocytes and monocytes by standard lab methods. Serum inflammatory proteins and adipokines, were quantified by multiplexed analysis using a luminometer (MAGPIX) at basal time (0) and after cessation (+6 months) of AC and paclitaxel regimen. RESULTS: There were no differences in age between the supplemented and the placebo groups (51.6y vs. 49.1y, p=0.4), neither in body mass index (BMI, 28.7 kg/m2 and 28.9 kg/m2, p=0.8). After 6 months of supplementation, patients who were supplemented with PUFAs had significant changes (time 0 vs 6, respectively) in total leukocytes (from 6.3 to 5.1 x103/mL, p =0.002) lymphocytes (from 33.5 to 25.2%, p =0.002), leptin (from 60.2 to 36.1 pg/mL, p=0.04) and adiponectin (from 36.8 to 43.3 mg/mL, p=0.05 ). On the other hand, placebo group had significant changes in the number of leukocytes (from 6.8 to 10.0 x103/mL, p =0.04), monocytes (from 6.7 to 10.1%, p=0.03) and an increase in leptin (from 22.7 to 46.3 pg/mL, p=0.04). CONCLUSIONS: Supplementation with 2.4g/d of EPA and DHA (ratio 2:1) during 6 months in Mexican LABC patients receiving NeoCT resulted in a less inflammatory status when compared to patients who received none. Our results clearly suggest that this type of supplementation may be beneficial to these type of patients. Currently, we are analyzing if treatment with omega-3 PUFAs are associated with lower incidence of side effects due to chemotherapy. Citation Format: DelaRosa-Oliva F, Ruiz-Garcia E, Gomez E, Arce-Salinas C, Lara-Medina F, Alvarado-Miranda A, Matus-Santos J, Flores-Díaz D, Deneken-Hernandez Z, Bargalló- Rocha J, Cabrera P, Guadarrama-Orozco J, Ruiz-Calzada H, Meneses-García A, Astudillo-de la Vega H. Effect of supplementation with eicosapentaenoic and docosahexaenoic omega-3 polyunsaturated fatty acid on the chemotoxicity in Mexican patients with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy (NeoCT) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-11-10.

Treatment of recurrent epithelial ovarian carcinoma with single-agent apatinib

: A 59-year-old woman was admitted and diagnosed as epithelial ovarian cancer. Postoperative pathological exam confirmed papillary adenocarcinoma. Then the patient received six cycles of chemotherapy with the regimen of paclitaxel plus nedaplatin. Two months after the last cycle, the recurrence of disease was revealed. Based on the gene detection revealing high expression of VEGF and low expression of RRM1, apatinib mesylate tablet was administered at a dose of 250 mg twice a day. During the administration of apatinib only manageable side effects occurred. About 8 months later a PET/CT scan suggested a partial remission of disease.

A phase II Study of FOLFOX versus POF (paclitaxel plus FOLFOX) versus IP PAC (intraperitoneal paclitaxel) plus FOLFOX as a first-line treatment in advanced gastric cancer (AGC): A feasibility analysis.

56 Background: Double regimens are commonly accepted for AGC in East Asia. However, triple regimens are recommended in west countries. POF regimen (a modified DCF reported in 2007, 2008, 2009, 2010 ASCO) appeared to be of good efficacy and was well tolerated in patients with AGC. Intraperitoneal paclitaxel showed high local concentration in abdominal cavity and low systemic toxicity. The aims of this study were to find out if the triplet POF was more effective with manageable side effects and IP PAC in combination with FOLFOX had higher local control rate and manageable systemic toxicity than doublet FOLFOX in AGC. Methods: The patients with AGC were randomized to three group. The FOLFOX regimen consisted of oxaliplatin 85 mg/m2, levoleucovorin 200 mg/m2, and 5-FU 400 mg/m2 bolus on day 1, then 5-FU 2400 mg/m2 continuous infusion over 46 hours. The POF regimen consisted of a 3-hour infusion of paclitaxel 135 mg/m2, followed by FOLFOX omitted 5-FU bolus. The IP PAC plus FOLFOX regimen consisted of paclitaxel 80 mg/m2 intraperitoneally plus FOLFOX. Every 14 days repeated for all three regimens. Up to 9 cycles of treatment were administered, followed by S-1 until disease progression Results: From 4th November 2015 to 10thJune 2016, 21 patients with ECOG PS 0-1 were assigned for the study. Grade ¾ toxicities, in the FOLFOX group (n = 7), neutropenia and nausea was one respectively; in the POF group (n = 9); neutropenia were two, stomatitis, nausea, vomiting, and fatigue was one respectively; in the IP PAC plus FOLFOX group (n = 5), neutropenia and fatigue was one respectively. No treatment-related death occurred. Median progression free survival and overall survival were 68 days and 194 days in FOLFOX group, 128 days and 282 days in POF group, 89 days and 178 days in IP PAC plus FOLFOX group. Conclusions: This pilot analysis showed three regimens including IP PAC plus FOLFOX had good safety profits. The POF group seemed to have better PFS and OS than the other two groups. This ongoing phase II study is feasible. Clinical trial information: NCT02845908.

Analysis of the factors influencing adjuvant chemotherapy decisions for triple negative breast cancer

Objective: To analyze adjuvant chemotherapy decisions for triple negative breast cancer (TNBC), and explore the influencing factors in the multidisciplinary treatment (MDT) modality. Methods: A retrospective analysis was performed. The cases with invasive TNBC who underwent surgery and MDT discussion for adjuvant treatment in Ruijin Hospital, from April 2013 to June 2015, were recruited. The patients' clinicopathological characteristics were analyzed and adjuvant treatment suggestions from MDT were obtained. Here the chemotherapy decision alteration was defined as a disagreement in chemotherapy or not, or inconsistence in regimens between the attending doctor and the multidisciplinary team. Results: A total of 194 patients aged ≤70 years old were enrolled in the multidisciplinary discussion, and 187 patients (96.4%) were suggested to receive chemotherapy. When compared the opinions of the attending doctor to suggestions of the multidisciplinary team, we found that the percentage of chemotherapy decision alteration reached 22.7% (39/172), of which 94.9% (37/39) were inconsistence in chemotherapy regimens. There were 119 patients who were recommended to receive epirubicin plus cyclophosphamide (EC) followed by docetaxel (T) or weekly paclitaxel (wP) regimens. Before the announcement of results for the E1199 trial, EC-T accounted for 62.5% (55/88), and EC-wP accounted for 37.5% (33/88) for this group of patients. After that, the proportion of EC-T was decreased to 22.6% (7/31) and proportion of EC-wP increased to 77.4%(24/31) (P<0.001). In addition, a total of 20 patients were suggested to receive platinum based chemotherapy. The proportions were 9.3% in cases with invasive ductal carcinoma, and 33.3% in cases with metaplastic carcinoma, respectively (P=0.016). Conclusions: The adjuvant chemotherapy decision for TNBC patients is altered in 22.7% of the patients after MDT discussion. After the announcement of SABCS E1199 results, more patients are suggested to receive EC followed by weekly paclitaxel. There is a lack of detailed evidence for platinum based adjuvant chemotherapy for TNBC, and more patients with metaplastic carcinoma receive platinum based adjuvant chemotherapy.

Efficacy and safety of duloxetine in Chinese breast cancer patients with paclitaxel-induced peripheral neuropathy.

Chemotherapy with paclitaxel is associated with significant neurotoxicity that may offset patients' quality of life and therapeutic benefits. This prospective, non-randomized control study evaluated the efficacy and safety of an antidepressant drug, duloxetine, at 30 or 60 mg/d, in the treatment of paclitaxel-induced peripheral neuropathy (PIPN) in Chinese breast cancer patients. A total of 102 patients with a median age of 50 (range, 25-60) years, treated in the Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, between November 2014 and January 2017 were finally enrolled. Stratified by baseline characteristics, the patients were classified into two groups, receiving either duloxetine or alternative anti-neurotoxicity drugs. During the course of the paclitaxel regimen, the eligibility criteria included sensory neuropathy, as evaluated by the National Cancer Institute-Common Toxicity Criteria for Adverse Events. The treatment consisted of receiving 30 mg duloxetine (for the first 4 weeks) and 60 mg duloxetine for an additional 8 weeks, or any other anti-neurotoxicity drug daily during the same crossover period. The improvement associated with PIPN from the patient's perspective were assessed by the Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) Scales, which contained questions scored from 0 to 4 (0, not at all; 4, very much; total score range, 0-44). Duloxetine was more effective in decreasing PIPN (odds ratio=5.426; 95% confidence interval, 1.898-15.514; P=0.002). Between duloxetine group and control group, the median (25th-75th percentiles) decreasing difference in the FACT-Tax pain score was 4 (2-6) vs. 1 (0-4) (P=0.005). Duloxetine is a promising and safe option with tolerable toxicity at a dose of 60 mg/d for Chinese breast cancer patients with PIPN. Non-neuropathy adverse events were mild and similar in both groups. The major toxicities of duloxetine included nausea, constipation, somnolence, dizziness and distention of the eyes. Further examination of the benefits of duloxetine in the prevention of PIPN is required.

320P Adjuvant chemotherapy comprising a paclitaxel and carboplatin regimen or paclitaxel and ifosfamide regimen for uterine carcinosarcoma, a single institutional retrospective study

320P Adjuvant chemotherapy comprising a paclitaxel and carboplatin regimen or paclitaxel and ifosfamide regimen for uterine carcinosarcoma, a single institutional retrospective study

Clinical efficacy and safety of nedaplatin combined with paclitaxel liposome in treatment of advanced esophageal cancer

Objective To observe the clinical efficacy and safety of nedaplatin combined with paclitaxel liposome on advanced esophageal cancer. Methods 80 advanced esophageal cancer patients were divided randomly into two groups, including study group treated with nedaplatin and paclitaxel liposome and control group of chemotherapy with nedaplatin and paclitaxel regimen with 3-week as a course of treatment. The clinical efficacy, quality of life and adverse reaction were compared between both groups after 2 courses of treatment. Results After two courses of treatment, the effective rates in study group and control group were 57.5% (23/40) and 55.0% (22/40), respectively, and there was no significant difference (χ2=0.704, P>0.05). The quality of life score before the treatment had no significant difference between the two groups (t=0.794, P>0.05). After one course of treatment, the quality of life was improved more than that in control group (t=5.782, P 0.05), but the incidences of nausea and vomiting, dyspnea, liver function, renal function damage in study group were significantly lower than those in control group, and the differences were statistically significant (P<0.05). Conclusions Besides a favorable function in retention paclitaxel original medicinal mechanism, efficacy and indications, paclitaxel liposome can effectively avoid the risk of adverse events. Furthermore, paclitaxel liposome combined with nedaplatin for advanced esophageal cancer is worthy of wide application, due to the better curative effect and safety. Key words: Esophageal neoplasms; Nedaplatin; Paclitaxel liposome; Safety

A network meta-analysis for toxicity of eight chemotherapy regimens in the treatment of metastatic/advanced breast cancer.

ObjectiveTo compare the incidence of toxicity of 8 different chemotherapy regimens, including doxorubicin + paclitaxel, doxorubicin, capecitabine, CMF (cyclophosphamide + methotrexate + 5-fluorouracil), FAC (fluorouracil + doxorubicin + cyclophosphamide), doxorubicin + docetaxel, doxorubicin + cyclophosphamide and paclitaxel in the treatment of metastatic/advanced breast cancer.ResultsThis network meta-analysis included 8 randomized controlled trials (RCTs). The findings revealed that, with regard to capecitabine alone regimen exhibited higher incidence of nausea/vomiting than doxorubicin + paclitaxel regimen, doxorubicin alone regimen and paclitaxel alone regimen in the treatment of patients with metastatic/advanced breast cancer (OR = 32.48, 95% CI = 1.65~2340.57; OR = 22.75, 95% CI = 1.03~1923.52; OR = 59.63, 95% CI = 2.22~5664.88, respectively). Furthermore, doxorubicin + cyclophosphamide regimen had lower incidence of febrile neutropenia than doxorubicin + docetaxel (OR = 0.17, 95% CI = 0.03~0.96). No significant difference in the incidence of stomatitis was observed among eight chemotherapy regimens.Materials and MethodsWe initially searched PubMed, Cochrane Library and Embase databases from the founding of these databases to January 2016. Eligible studies investigating the 8 different chemotherapy regimens for treatment of metastatic/advanced breast cancer were included for direct and indirect comparison. The odds ratio (OR) and surface under the cumulative ranking curves (SUCRA) value of the incidence of toxicity among eight chemotherapy regimens were analyzed.ConclusionsCapecitabine alone regimen and doxorubicin + docetaxel regimen may have a more frequent toxicity in the treatment of metastatic/advanced breast cancer.

46TiP - AIPAC (Active Immunotherapy PAClitaxel): A phase IIb trial in hormone receptor-positive metastatic breast carcinoma patients receiving IMP321 (LAG-3Ig fusion protein) or placebo as adjunctive to a standard chemotherapy regimen of paclitaxel

46TiP - AIPAC (Active Immunotherapy PAClitaxel): A phase IIb trial in hormone receptor-positive metastatic breast carcinoma patients receiving IMP321 (LAG-3Ig fusion protein) or placebo as adjunctive to a standard chemotherapy regimen of paclitaxel

861P - ICON8 Stage 1A and 1B analysis: safety and feasibility of weekly carboplatin and paclitaxel regimens in first-line ovarian cancer

861P - ICON8 Stage 1A and 1B analysis: safety and feasibility of weekly carboplatin and paclitaxel regimens in first-line ovarian cancer

Frequency of Chemotherapy Induced Anemia in Breast Cancer Patients

Background: Breast cancer is the second most common malignancy in women, worldwide. Several etiologic factors may cause anemia in a patient with breast cancer. Anemia is a prevalent complication in patients with breast cancer who undergo chemotherapy which affects the health status and quality of life in these patients. The aim of this study was to evaluate the prevalence of anemia in patients with non-metastatic breast cancer who underwent adjuvant chemotherapy. Methods: In this cross-sectional study, 144 women with non-metastatic breast cancer who referred to radiotherapy and oncology department of Imam Reza hospital and met inclusion criteria were included. Data were obtained from patients’ archived documents and were analyzed by SPSS software (version16). Results: In this study, 41% of patients were anemic before the chemotherapy and 43.1% of patients became anemic during and after treatment. The prevalence of post-chemotherapy anemia was significantly higher in advanced stages of cancer (P = 0.01). The chance of developing anemia were more in patients who underwent 8 cycles and AC + paclitaxel regimen, compared to the ones with 6 cycles and other regimens. There was no significant relationship between the prevalence of anemia and type of chemotherapy regimen, number of chemotherapy cycles, positive lymph nodes, co-morbidities, menstrual status, and body mass index (BMI). Conclusions: Due to the high prevalence of chemotherapy-induced anemia and its effects on quality of life, even mild degrees of anemia should be detected and evaluated before treatment. Considering early interventions is of cardinal importance, especially in the elderly.

Knockdown of Hypoxia-Inducible Factor 1α Improved the Efficacy of Low-Dose Metronomic Chemotherapy of Paclitaxel in Human Colon Cancer Xenografts.

Low-dose metronomic chemotherapy represents a new strategy for solid tumor treatments with a strong antiangiogenic activity and few side effects. However, low-dose metronomic therapy alone is not always as effective as traditional chemotherapy on eradication of tumor. On the contrary, low-dose metronomic in some cases could stimulate tumor growth due to hypoxia of tumor cells induced during therapy. Our study aimed to investigate whether knockdown of hypoxia-inducible factor-1α expression in tumor cell could facilitate low-dose metronomic therapy with paclitaxel for human colon cancer. Human colon cancer cell line (HT-29) stably transfected with specific short hairpin RNAs silencing hypoxia-inducible factor-1α exhibited marked attenuation of hypoxia-induced expression of the target genes such as vascular endothelial growth factor, glucose transporter 1, and P-glycoprotein. Compared with HT-29-c xenograft tumor model established by subcutaneous injection of HT-29 cells stably transfected with scrambled control short hairpin RNA, HT-29-ih xenograft tumor model showed more significant and long-lasting antitumor responses of empirical metronomic paclitaxel regimens, accompanied by drastic angiogenesis decrease and neglectable toxicity. All these data indicated that the combination of paclitaxel low-dose metronomic therapy with hypoxia-inducible factor-1α knockdown might provide a potent battle against colon cancer.

A nomogram for predicting pathological complete response in patients with human epidermal growth factor receptor 2 negative breast cancer

BackgroundThe response to neoadjuvant chemotherapy has been proven to predict long-term clinical benefits for patients. Our research is to construct a nomogram to predict pathological complete response of human epidermal growth factor receptor 2 negative breast cancer patients.MethodsWe enrolled 815 patients who received neoadjuvant chemotherapy from 2003 to 2015 and divided them into a training set and a validation set. Univariate logistic regression was performed to screen for predictors and construct the nomogram; multivariate logistic regression was performed to identify independent predictors.ResultsAfter performing the univariate logistic regression analysis in the training set, tumor size, hormone receptor status, regimens of neoadjuvant chemotherapy and cycles of neoadjuvant chemotherapy were the final predictors for the construction of the nomogram. The multivariate logistic regression analysis demonstrated that T4 status, hormone receptor status and receiving regimen of paclitaxel and carboplatin were independent predictors of pathological complete response. The area under the receiver operating characteristic curve of the training set and the validation set was 0.779 and 0.701, respectively.ConclusionsWe constructed and validated a nomogram to predict pathological complete response in human epidermal growth factor receptor 2 negative breast cancer patients. We also identified tumor size, hormone receptor status and paclitaxel and carboplatin regimen as independent predictors of pathological complete response.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2652-z) contains supplementary material, which is available to authorized users.

The role of oncoplastic breast conserving treatment for locally advanced breast tumors. A matching case-control study.

BackgroundBreast conserving surgery (BCS) after neoadjuvant chemotherapy (NC) in patients with locally advanced breast cancer (LABC) is an infrequent procedure. In these patients the association with BCS and oncoplastic surgery (OS) is reported as a possible procedure in case-series, but there are limited case-control studies.MethodsA matched case-control study evaluated LABC submitted to NC and BCS. We evaluated 78 patients submitted to doxorubicin-cyclophosphamide regimen followed by paclitaxel regimen. The match case-control proportion was 2:1 and the patients were selected by tumor size, clinical T stage and year of diagnosis.Results52 underwent classic BCS and 26 OS. The average size tumor was 5.25 cm and 88.5% of the tumors were larger than 3 cm. The clinical and pathological group characteristics were similar, except the weight of surgical specimens (p = 0.004), and surgical margins (p = 0.06), which were higher in OS group. The rate of complete pathologic response was 26.9%. 97.4% received postoperative radiotherapy. At 67.1 months of follow up, 10.2% had local recurrence (LR) and 12.8% locoregional recurrence (LRR) and 19.2% died because disease progression. The overall survival at 60 months was 81.7%. After surgery the disease free-survival at 60 months was 76.5%. The was no difference between groups related to pathologic response (p = 0.42), LR (p = 0.71), LRR (p = 1.00), overall survival (p = 0.99) and disease specific survival (p = 0.87).ConclusionThis study corroborates the fact that OS is a safety procedure for LABC, offering the similar oncologic results observed in patients submitted to classic BCS.