CP Regimen Research Articles

First-line immunosuppressive therapies for acquired hemophilia A: A 25-year cohort experience and network meta-analysis

Acquired hemophilia A (AHA) presents a significant bleeding risk. Management involves bleeding control and immunosuppressive therapy (IST) to eliminate inhibitors. This study, encompassing a retrospective cohort of 76 newly diagnosed AHA patients (1997–2022), evaluated IST outcomes such as complete remission (CR), relapse, and mortality rates, alongside influencing factors. Supplementing these findings, a systematic review and network meta-analysis compared CR and relapse rates across ISTs, sourcing from Embase, Scopus, and ScienceDirect up to November 2023. In our cohort, demarcated by a 20 Bethesda-unit titer threshold, cyclophosphamide plus prednisolone (CP; n = 64) was the predominant initial IST. Lower inhibitor levels significantly correlated with higher CR rates (86.8 % vs 62.2 %; P = .014) and showed an odds ratio of 0.26 for CR (P = .021). Median relapse-free survival (RFS) extended to 37.13 months, significantly enhanced by CP (hazard ratio, 0.24; 95 % confidence interval, 0.10–0.60; P = .002). Our network meta-analysis, including 1476 CR and 636 relapse patients, indicated CP and rituximab-based ISTs significantly outperformed steroid monotherapy in terms of CR and lower relapse rates (risk differences of 0.15 and −0.13/−0.15, respectively; P < .05), without significant differences between CP and rituximab. Moreover, adding rituximab to the front-line treatment did not produce superior outcomes compared to the CP regimen alone, positioning CP as a viable first-line choice, particularly where rituximab is less accessible. The consideration of IST toxicity remains critical in treatment decisions.

Comparison of the quality of life of patients with a beta-thalassemia major, regularly receiving parenteral and oral chelators

Patients with β-thalassemia major (Mβ-th) are transfusion-dependent, which affects their quality of life . To maintain a safe level of iron in the body, patients with Mβ-th require adequate regular therapy with chelation drugs (CP). Currently, for the correction of iron overload in patients with Mβ-th, along with oral CP, parenteral CP continues to be used. However, oral and parenteral CP are perceived by patients ambiguously. Comparative assessment of the quality of life of transfusion-dependent children with Mβ-th receiving various CPs: parenteral deferoxamine and oral deferasirox. For 2 years, a survey and clinical observation of 201 children with Mβ-th aged 2 to 18 years (boys 128, girls 73) was conducted. The control group consisted of apparently healthy children from preschool and school institutions (n=30). Patients with Mβ-th underwent a quality of life study (PedsQL- Pediatrics Quality of Life Inventory, Generic Core Scales and PedsQLTM4.0) and a psychological examination.The survey was conducted after obtaining the informed consent of the parents of older children at the beginning and at the end of the study. Once a month, the necessary clinical and biochemical analyzes were carried out.Patients with Mβ-th regularly prescribed various CP regimens: deferoxamine subcutaneously; deferasirox, orally. All studied patients with Mβ-th were divided into four age groups: group 1 - children under 4 years old according to parents (n=41); group 2 - children 5-7 years old according to the assessment of children and parents separately (n=62); group 3 - children 8-12 years old according to the assessment of children and parents separately (n= 47); Group 4 - children aged 13-18 years old according to the assessment of children and parents separately (n=51). Each of the 4 groups of Mβ-th patients was divided into a subgroup taking only deferiprone and a subgroup taking only deferasirox. According to the Results of the survey, the indicators of the quality of life and the psychological state of children with Mβ-th receiving parenteral and oral CP differed. So, in sick children with Mβ-th of different age groups, when taking parenteral CP in comparison with those taking oral CP, the quality of life was reduced, and the psychological state worsened significantly. This was especially impacted patients in the group of 8-13 years. In this group, there were more complex relationships with peers, parents, there was an increase in anxiety and aggressiveness, which is associated with the need for hours of use of the pump for subcutaneous injection of the drug, the presence of pathology that limits the use of oral chelators. In children of 4 different age groups, there is a significant difference in the values given by patients and their parents to the quality of life in patients receiving parenteral and enteral chelator therapy.

Feasibility and Safety of 3-Weekly Carboplatin/Paclitaxel Regimen in Advanced Squamous cell Carcinoma of the Anal Canal

Introduction: Anal cancer is a rare disease, and there is a lack of phase 3 studies in the advanced setting. Currently, the standard treatment is based on interAACT phase 2 study using Carboplatin (C) (AUC 5, D1q28) plus Paclitaxel (P) (80 mg/m2, D1,8,15q28). This study demonstrated a median OS of 20m, a response rate of 59% and serious adverse events in 36% of patients (pts). However, this regimen requires more infusions and hospital visits than a 3-weekly CP regimen, resulting in high social and financial cost. Objective: To retrospectively access safety and efficacy of treatment with 3-weekly CP in advanced SCCA. Methods: We performed a single-center retrospective analysis of patients (pts) who received first-line treatment with 3-weekly CP for inoperable locally recurrent or metastatic SCCA between Jun/2011 and Jun/2018. Study data were collected using REDCap®. Survival analyses were estimated with the Kaplan-Meier method and compared by log-rank test. Prognostic factors were evaluated by Cox regression. Results: 47 patients were included. Median age was 57 years, 60% (n=28) were female and 21% (n=10) HIV positive.16% (n=7) had metastatic disease at diagnosis. The majority of pts (n=42) were treated with paclitaxel (P) 175 mg/m2 plus carboplatin (C) AUC 5 every 3 weeks. The median number of cycles was 4 and dose reduction by toxicity was necessary for 30% (n=14). Grade 3/4 adverse events were neutropenia 19% (n=9), anemia 4% (n=2), fatigue 4% (n=2), neuropathy 2% (n=1). Two pts had interruption due to toxicity and no treatment-related death. 64% of patients benefited from treatment, 4% with complete response. The median overall survival (OS) was 10 months(m). In a multivariable analysis, HIV-positive (HIV+) status (HR 3.1; 95%CI 1.8-8.4; p 0.001) and ECOG 2/3 (HR 3.9; 95%CI 1.2-8.1; p 0.01) showed a negative impact on OS. Median OS was 16m for HIV- vs 4m for HIV+ group; and 20m for ECOG 0/1 vs 4m for ECOG 2/3. Conclusion: The present study suggests that 3-weekly CP has similar outcomes to the InterAACT regimen. Nevertheless, pts who are HIV+ or have ECOG 2/3 had poor outcomes and other treatment strategies should be studied for these pts.

A phase I open-label study of selinexor with paclitaxel and carboplatin in patients with advanced ovarian or endometrial cancers

PurposeSelinexor, a selective inhibitor of nuclear export, monotherapy causes nuclear accumulation of tumor-suppressor proteins and has anti-tumor activity in ovarian and endometrial cancers. The safety and tolerability of oral selinexor plus intravenous carboplatin and paclitaxel chemotherapy (selinexor + CP) was evaluated in this population. Patients and methodsThis phase I, 3 + 3 dose-escalation study assessed 4 selinexor + CP regimens. Patients in cohorts of 3, regardless of disease type, were administered 1 of 4 alternating regimens (selinexor at 30 mg/m2 or 60 mg plus CP at AUC 5 and 175 mg/m2 or 80 mg/m2, respectively) for 6–10 cycles (1 cycle = 21 days), followed by selinexor maintenance. Enrolled patients with ovarian cancer had received 1 prior platinum-based therapy. Patients with endometrial cancer were chemotherapy-naive or had received 1 prior platinum-based therapy. Response was evaluated every 9 weeks. ResultsTwenty-three patients were treated (5 serous ovarian cancer; 18 endometrial cancer, including 6 carcinosarcomas). The most common treatment-related adverse events (TRAEs) were thrombocytopenia (100%), leukopenia (91%), and hyperglycemia (87%). The most common grade 3/4 TRAEs were leukopenia (70%), neutropenia (70%), lymphopenia (61%), anemia (57%), and alanine transaminase increase (43%). One treatment-related dose-limiting toxicity (grade 3 syncope) occurred. Twelve patients achieved a partial response and 1 achieved a complete response. Responses to all four regimens were observed in ovarian and endometrial cancers. ConclusionsCombination selinexor + CP was safe and tolerated in advanced ovarian and endometrial cancers.

A Retrospective Study on Prephase Therapy Prior to Definitive Multiagent Chemotherapy in Aggressive Lymphomas

Background: Diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL) are aggressive lymphomas that evolve rapidly and are fatal if untreated. Most treatment-related toxicities occur during the initial phase of therapy, particularly in the elderly and in patients with a high disease burden. Prephase therapy is used as a preventive strategy prior to definitive multiagent chemotherapy to ameliorate the development of toxicity, such as febrile neutropenia, tumor lysis syndrome, deterioration in performance status, and death. While this approach is often implemented, there are few data supporting when to initiate a prephase regimen, or whether this approach will be effective. We present data from our experience at the University of North Carolina Cancer Hospital.Methods: We conducted a retrospective analysis of patients (pts) diagnosed with DLBCL and BL between January 2016 and December 2017. Pts were divided into ‘prephase’ (PP) and ‘non-prephase’ (NPP) groups. The PP group received either prednisone (P) alone at 60 mg/kg oral daily from day -6 to day -1, or in combination with vincristine (V) 1 mg intravenously on day -6 (VP regimen), cyclophosphamide 200 mg/m2 on day -6 (CP regimen), or all three drugs (CVP regimen). Multiagent chemotherapy was given at day 0. Both groups were evaluated until day 30. ECOG performance status (PS), grade 3-4 cytopenias, absolute neutrophil count (ANC) and platelet nadirs, time to ANC and platelet recovery, episodes of febrile neutropenia, hospitalization and emergency (ER) visits, and next cycle dose reduction or delay, were compared in both groups.Results: Ninety-two pts (DLBCL n=82, and BL n=10) were identified. Clinical characteristics are shown in Table 1. Twenty-two pts received PP therapy (vs. NPP n=70). Median age at diagnosis was 59 years and 61 years for PP and NPP group, respectively. Female predominance was observed in both groups (PP 59% and NPP 54%). Poor baseline ECOG PS was significantly different between the PP and NPP group (median score 2 vs. 0, p<0.001). Stage III-IV and bulky disease were more common in the PP group, although this was not statistically significant. Oral prednisone was the most common prephase therapy used (P n=17, VP n=1, CP n=1, CVP n=3). All regimens were well tolerated. Definitive chemotherapy regimens and outcomes are summarized in Table 2. The PP group had a significant improvement in PS from a median PS of 2 at baseline to a median PS of 1 (p<0.001) by day 14. The NPP group did not have a significant change in PS. In a subgroup analysis, both pts older than 60 years with any PS (n=10, p=0.027), and pts 60 years or younger with a PS of 2 or more (n=6, p=0.023) had a significant improvement in PS after prephase therapy. PP pts had a shorter time for ANC and platelet count recovery than NPP pts (ANC 4 vs. 8 days, p=0.013; platelet 4 vs. 9 days, p=0.023). The platelet nadir was significantly lower in the PP (80 x 109 plt/L) compared to the NPP group (150 x 109 plt/L) (p=0.025). There was no significant difference in the episodes of febrile neutropenia.Conclusions: Prephase therapy significantly improved PS by day 14 of definitive multiagent chemotherapy at first cycle. The overall improvement in PS was primarily caused by improvements in 2 groups: pts older than 60 years, and pts 60 years or younger with poor PS (ECOG PS 2 or more). This is consistent with who we would expect to benefit the most from prephase therapy. Patients who received prephase therapy had a significant reduction in the length of their ANC nadir, although, interestingly, the rate of febrile neutropenia was low in both arms. The length of the platelet nadir was also significantly reduced in the PP group. Conversely, the depth of platelet nadir was significantly lower in the PP group, which may be a reflection of more aggressive disease in this group. The prephase group trended towards a reduction in the number of hospital admissions, ER visits, and next cycle dose reduction or delays, but these did not reach statistical significance. Based on these results, we will implement a provider reminder to consider prephase therapy when using multiagent chemotherapy in pts with aggressive lymphomas older than 60 years, or pts <60 with PS of 2 or greater. [Display omitted] DisclosuresGrover:Seattle Genetics: Consultancy. Dittus:Seattle Genetics: Consultancy.

Hematological toxicity of carboplatin for gynecological cancer according to body mass index.

The aim of the present study was to analyze how patient weight affects the hematological toxicity of carboplatin and whether this toxicity is more prevalent in overweight patients. We performed a retrospective 2-year study of patients diagnosed with a gynecological cancer and whose treatment regimen contained carboplatin (AUC dose=5 or 6) and paclitaxel (dose=175mg/m(2)) every 3weeks (CP scheme). We recorded all severe hematological events (thrombocytopenia, neutropenia, and/or anemia grade III/IV) according to the CTCAE v4.03, as well as treatment modifications and the need for granulocyte colony-stimulating factors (G-CSF) and/or erythropoietin (EPO) or packed red blood cells (PRBC). Patients with a body mass index (BMI) ≥27kg/m(2) were considered as overweight (OW) and those with a BMI <27kg/m(2) were considered as normal weight (NW). Fifty-two patients met the inclusion criteria (21 patients in the OW group, 31 patients in the NW group). The OW group showed a higher incidence of thrombocytopenia (95% confidence intervals (CI) 1.51-27.72; p<0.02) and anemia (95% CI 1.06-33.63; p<0.05). Moreover, this was reflected in a greater number of changes in the usual CP regimen (95% CI 2.19-44.32; p<0.01). The need for G-CSF and/or EPO/PRBC was also significantly higher in the OW group (95% CI 1.08-12.16; p<0.04). Carboplatin dosing based on real weight in obese patients resulted in increased hematologic toxicity, mainly thrombocytopenia. Dose adjustment based on other descriptors of weight, such as adjusted weight, may be better tolerated by patients. However, future studies are needed to demonstrate not only better safety of carboplatin but also improved survival rates.

Randomized Phase II Trial Comparing Carboplatin Plus Weekly Paclitaxel and Docetaxel Alone in Elderly Patients With Advanced Non-Small Cell Lung Cancer: North Japan Lung Cancer Group Trial 0801

Standard first-line chemotherapy for elderly non-small cell lung cancer (NSCLC) patients has been monotherapy with vinorelbine or gemcitabine. Docetaxel has also been considered as an alternative option for the elderly population in Japan. We have previously demonstrated the high efficacy of carboplatin plus weekly paclitaxel for elderly NSCLC patients. Consequently, we conducted a randomized phase II study to select the proper regimen for a future phase III trial. Eligible patients were aged 70 years or older with newly diagnosed advanced NSCLC. Patients were randomly assigned either to a combination of carboplatin (area under the curve: 6 mg/mL per minute) with weekly paclitaxel (70 mg/m²) (CP regimen) or to single-agent docetaxel (60 mg/m²). The primary endpoint of this study was objective response rate. Secondary endpoints were progression-free survival, overall survival, and toxicity profile. Among 83 eligible patients (41 to CP, 42 to docetaxel), the objective response rates were 54% (95% confidence interval: 39%-69%) and 24% (95% confidence interval: 11%-37%) and median progression-free survival was 6.6 months and 3.5 months in the CP arm and the docetaxel arm, respectively. Severe neutropenia, febrile neutropenia, and nausea were significantly frequent in the docetaxel arm, whereas toxicities in the CP arm were generally moderate. One treatment-related death was observed in the docetaxel arm. The CP regimen achieved higher activity with less toxicity than single-agent docetaxel. Considering the results of this phase II trial and the IFCT-0501 trial, we have selected the CP regimen for a future phase III trial in elderly patients with advanced NSCLC.

Continuous low-dose cyclophosphamide and prednisone in the treatment of relapsed/refractory multiple myeloma with severe heart failure

Patients with relapsed/refractory (R/R) multiple myeloma (MM) complicated by severe heart failure typically do not tolerate conventional chemotherapy. Our previous study indicated that R/R MM patients with severe comorbidities could benefit from continuous low-dose oral cyclophosphamide and prednisone (CP regimen). We hereby performed a study of 56 R/R MM patients with severe heart failure (New York Heart Association class ≥ III) receiving the treatment of CP regimen. Among the 54 evaluable patients, clinical benefit was noted in 63.0% (complete response, 3.7%; very good partial response, 7.4%; partial response, 48.1%; stable disease, 3.7%). The median overall survival (OS) and progression-free survival (PFS) were 8 and 6 months. The left ventricular ejection fraction (LVEF) and the serum levels of B-type natriuretic peptide (BNP) were improved significantly. Slight adverse events were observed. In summary, the CP regimen is effective in R/R MM patients complicated with severe heart failure.

Changes in protein level for bobwhite quail

SUMMARY Limited information exists concerning the dietary requirements of bobwhite quail (Colinus virginianus), and producers who rear this species for sport shooting and stocking could benefit from such information. In this experiment, 576 two-week-old bobwhite quail were divided among 6 treatment groups and randomized into 8 replications with 12 birds/replicate. A 26, 24, or 22% CP diet (2,810 kcal of ME/kg) was fed to 4 or 6 wk of age, followed by the introduction of a 20% CP diet (2,810 kcal of ME/kg) fed through 8 wk of age. Birds and feed were weighed on a biweekly basis. No differences were observed in BW or gain of birds fed the 3 CP regimens from 2 wk until introduced to a 20% CP diet. Feed consumption was significantly decreased in the 22% CP group that was introduced to the lower CP diet (20%) after 2 wk. Although this treatment exhibited a marginally low protein intake as compared with the other treatments, growth performance remained uncompromised. Period FCR appeared to be unaffected by dietary CP regimen, but overall FCR for the 8-wk period was highest for birds on the 26% CP regimen (3.824), whereas the 22% CP regimen was intermediate (3.768), and the 24% CP regimen provided the best FCR (3.639). Therefore, bobwhite quail appear to be unaffected by major dietary changes in protein level and a 26% CP diet may provide adequate nutrition for the 0- to 2-wk starting period, followed by a 24% CP diet for a 2- to 4-wk period, and a 20% CP diet thereafter.

Clinical effect of low-dose cyclophosphamide and prednisone in treatment of multiple myeloma and its influence on serum VEGF, PDGF-BB levels

Objective To investigate the clinical effect of low-dose cyclophosphamide plus prednisone(CP regimen) in treatment of multiple myeloma(MM) and its influence on serum levels of vascular endothelial growth factor(VEGF) and platelet-derived growth factor BB(PDGF-BB).Methods Totally 54 patients with refractory or relapse MM were continuously treated with CP regimen: oral cyclophosphamide(CTX,50 mg/d) and prednisone(Pred,15 mg/d).The peripheral blood samples were collected from each group 0,2,4,and 6 months after treatment.Serum VEGF and PDGF-BB levels were analyzed by ELISA.Results The overall effective rate was up to 69%(36/52) in our study.The treatment was effective in 30 patients,including 2 complete response(CR) cases,4 very good partial response(VGPR) cases and 24 partial response(PR) cases,and their serum samples were examined for 4 times.The serum levels of VEGF and PDGF-BB were significantly decreased in the 30 patients at 2,4,and 6 months after treatment(P0.01);while their levels were not significantly change in the 7 invalid patients 2 months after treatment compared with before treatment.Conclusion Low-dose cyclophosphamide plus prednisone has noticeable effect in treatment of MM patients;it can also greatly down-regulate serum VEGF and PDGF-BB levels.The mechanisms of CP regimen in MM patients may be associated with the inhibition of new blood vessel generation.

Comparison of the pharmacokinetics differences between the combination of cyclophosphamide and cisplatin and single medication

Objective To investigate the pharmacokinetic difference between the combination of cyclophosphamide and cisplatin and single medication.Methods High performance liquid chromatography (HPLC) was used to detect the pharmacokinetic parameters and distribution parameters in tissue of cisplatin and cyclophosphamide.Results The pharmacokinetic curve of the CP regimen showed two-compartment model,and there was no significant difference between the absorption half life of the combination of the two drugs (0.56±0.02,0.72±0.02) and that of single medication (0.92±0.02,1.16±0.12) (t =2.091,t =2.379,both P ＞ 0.05).While the elimination half life of the combination (0.56±0.02,0.72±0.02) was significantly longer compared with that of single medication (0.92±0.02,1.16±0.12) and there were significant differences (t =5.796,t =6.213,both P ＜ 0.05).There was no significant difference of MRT in heart between the disturbution of the combination of the two drugs and that of single medication (t =2.231,t =2.096,both P ＞ 0.05).While there was significantly longer compared with that of single medication and there were significant differences in lung and liver (t =5.976,t =6.270,both P ＜ 0.05).Conclusion When used in combination,the elimination of the drugs is slower,which suggests that the interval and dosage of the drugs should be adjusted to their pharmacokinetic parameters in clinical use to improve effects and lower side effects. Key words: Cyclophosphamide; Cisplatin; Pharmacokinetics; Comparative effectiveness research

1274P - ALK and EGFR Mutation Analysis in a Phase II Trial of Cisplatin/Pemetrexed in Japanese Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer

ABSTRACT Background Recently, ethnic differences and genotypes such as EGFR mutation or fusion gene (ALK translocation) are important factors in non-small cell lung cancer (NSCLC) treatment. Pemetrexed (P)/cisplatin (C) is one of the standard treatments for advanced non-squamous (Nsq) NSCLC. However, the efficacy of the CP regimen has not been well examined in Japanese Nsq NSCLC patients; furthermore, the difference in efficacy between genotypes was not thoroughly examined. Therefore, the present study was conducted to evaluate the efficacy of the CP regimen in Japanese Nsq NSCLC patients, and to determine whether EGFR mutation and ALK translocation impacted the treatment. Methods This study was conducted from May 2009 to December 2010. Patients were eligible for this study if they had histologically or cytologically confirmed recurrent or metastatic Nsq NSCLC previously untreated with chemotherapy, an ECOG performance status of 0 or 1, life expectancy of more than 12 weeks, and adequate organ function. Patients received C (75 mg/m2) plus P (500 mg/m2) on day 1 every 3 weeks. Of the 50 patients initially enrolled, 49 were evaluated, and 43 tumor samples were available for analysis. Most patients were male (80%), and 80% of the patients had adenocarcinoma. The primary endpoint was the response rate that was evaluated. according to RECIST. EGFR mutation was examined using PCR-based methods, and the ALK fusion protein was examined using a highly sensitive IHC method in the available tumor specimens. Results The objective response rate and disease control rate in all patients were 44.9% and 79.6%, respectively. The median progression-free survival was 4.4 months, and the 1-year survival was 73.5%. Toxicities were mild; no new toxicity profile was identified. Among the 43 samples, the following mutations were identified: 9 EGFRm (21%), 5 ALK (12%), and 29 wild-type (67%). Objective response was observed in 6 (66.7%) EGFRm, 2 (40%) ALK (+), and 13 (44.8%) wild-type mutations. Conclusion Although the CP regimen demonstrates consistent efficacy in Japanese Nsq NSCLC patients, EGFR mutation and ALK translocation may have impacted this treatment. Disclosure All authors have declared no conflicts of interest.

ALK and EGFR mutation analysis in a phase II trial of cisplatin/pemetrexed in Japanese patients with advanced nonsquamous non-small cell lung cancer.

e18017 Background: Recently, ethnic differences and genotypes such as EGFR mutation (EGFRm) or fusion gene (ALK translocation: ALKt) are important factors in non-small cell lung cancer (NSCLC) treatment. Pemetrexed (P)/cisplatin (C) is one of the standard care for advanced non-squamous (Nsq) NSCLC. However, the efficacy of the CP regimen has not been well examined in Japanese Nsq NSCLC patients (pts); furthermore, the difference in efficacy between genotypes was not thoroughly examined. Therefore, the present study was conducted to evaluate the efficacy of the CP regimen in Japanese Nsq NSCLC pts, and to determine whether EGFRm and ALKt impacted the treatment. Methods: This study was conducted from May 2009 to December 2010. Pts were eligible for this study if they had histologically or cytologically confirmed recurrent or metastatic Nsq NSCLC previously untreated with chemotherapy, an ECOG performance status of 0 or 1, life expectancy of more than 12 weeks, and adequate organ function. Pts received C (75 mg/m2) plus P (500 mg/m2) on day 1 every 3 weeks. Of the 50 pts initially enrolled, 49 were evaluated, and 43 tumor samples were available for analysis. Most pts were male (80%), and 80% of the pts had adenocarcinoma. The primary endpoint was the response rate that was evaluated according to RECIST. EGFRm was examined using PCR-based methods, and the ALK fusion protein was examined using a highly sensitive IHC method in the available tumor specimens. Although the CP regimen demonstrates consistent efficacy in Japanese Nsq NSCLC pts, EGFRm and ALKt may have impacted this treatment. Results: The objective response rate and disease control rate in all pts were 44.9% and 79.6%, respectively. The median progression-free survival was 4.4 months, and the 1-year survival was 73.5%. Toxicities were mild; no new toxicity profile was identified. Among the 43 samples, the following mutations were identified: 9 EGFRm (21%), 5 ALKt (12%), and 29 wild-type (67%). Objective response was observed in 6 (66.7%) EGFRm, 2 (40%) ALKt, and 13 (44.8%) wild-type. Conclusions: Although the CP regimen demonstrates consistent efficacy in Japanese Nsq NSCLC pts, EGFRm and ALKt may have impacted this treatment.

Neutropenic complications with carboplatin AUC 5 and paclitaxel 175 mg/m2 (CP) regimen in Indian patients: A community-based single center experience.

e19607 Background: In most oncology clinical trials, the majority of patients are of Caucasian ethnicity. It is often difficult to apply the same chemotherapy with equal dose intensity in Indian patients due to increased risk of complications. The exact incidence of complications &amp; whether the difference in chemotherapy tolerability is due to genetic or environmental factors remain unclear. We provide a community-based single center experience with the commonly used CP regimen in Indian patients. Methods: A retrospective study of all patients who received CP regimen (Cockroft Gault formula for CrCl) from September 2010 to December 2011 was undertaken. Incidence of neutropenic complications, G-CSF utilization &amp; pRBC transfusion was determined. Results: Fifty six patients received 194 cycles of CP (range 1-8 cycles, median 3 cycles, mean paclitaxel dose 256mg, mean carboplatin dose 431mg, average BSA 1.56). Clinical characteristics : male 16, female 40; age range 34 - 82 yrs, median 55 yrs; site - breast 6, ovary 19, cervix/uterus 11, esophagus 8, others 12; stage – I/II/III 7, IV 42; histology – SCC 21, Adenoca 34. After the 1st cycle, there were 8 neutropenic complications (14%)- 4 patients (7%) with neutropenia (ANC&lt;1500 cells/mm3) and 4 patients (7%) with neutropenic fever. Forty-two patients received the 2nd cycle, &amp; in total 12 patients required G-CSF support (28%). There were 3 deaths, 2 due to neutropenic fever &amp; sepsis. Average baseline hemoglobin was 11.5gm/dl with 5 episodes of pRBC transfusion. Conclusions: Although the incidence of neutropenia in Indian patients receiving CP is not higher than previous reports (20-25%), there is a much higher incidence of neutropenic fever (over the reported 1-2%) &amp; death, resulting in high G-CSF utilization. This raises several issues such as the role of prophylactic antibiotics, impact of environmental &amp; socio-economic factors (compromised nutritional status &amp; hygiene, lack of disease insight &amp; lack of access to urgent health care). We will need to implement additional measures, increase patient &amp; family awareness by frequent education &amp; counseling so as to reduce complications &amp; improve clinical outcomes in Indian patients.

Seasonal and nutrients intake regulation of lipoprotein lipase (LPL) activity in grazing yak ( Bos grunniens) in the Alpine Regions around Qinghai Lake

Lipoprotein lipase (LPL) is considered as a key enzyme in the lipid deposition and metabolism in tissues. To better understand fat cycling in grazing yak to adapt to the harsh environment on the Qinghai-Tibetan Plateau, and we have therefore explored seasonal and nutritional regulation of LPL in adipose tissue, liver and skeletal muscle. Sixty 3 year old growing yaks (BW. 120.3 ± 15.28 kg) were subdivided into six groups, each used to determine effects on chemical body composition and LPL activity in different tissues. The alpine pastures had the highest Crude protein (CP, 11.06%) contents and the gross energy (GE, 11.49 MJ/kg) in summer. Growth rates and body fat content were responsive to CP and GE intake regimen. Late spring up-regulation of LPL activity in the subcutaneous adipose tissue was consistent with a pronounced increase of body weight (BW) and whole body fat content. The highest LPL activity in the skeletal muscle was found in September (774 ± 64.1 mU/g tissue), which may serve to cover the increased energy demands for compensatory growth and maintenance of adiposity in the coming cold season. Furthermore, the seasonal regulation of LPL involves some factors in addition to insulin and triglycerides (TG). These results suggest that yaks could rely, in part, on LPL activity to adapt to the harsh forage environment. During the growing season, an enhanced synthesis of LPL production in the adipose tissues along with mechanisms for the recycling of fat contributes toward the rapid recovery of body weight.

Continuous Administration of Low-Dose Cyclophosphamide and Prednisone as a Salvage Treatment for Multiple Myeloma.

Abstract 4962 ObjectiveTo assess the efficacy and tolerability of continuous low-dose cyclophosphamide and prednisone regimen (CP) as a salvage therapy for multiple myeloma (MM). MethodThe CP regimen consisted of oral cyclophosphamide at 50 mg and prednisone at 15 mg daily. A total of 27 consecutive patients received the CP regimen: 19 patients had severe comorbid conditions; 8 were unwilling to continue conventional chemotherapy due to severe infection associated with conventional treatment. All patients had received 1-4 chemotherapeutic regimens prior to the current study. ResultThe overall response rate (complete remission, very good partial response, and partial response) was 66.7%. The median time to response was 2 months. In the patients who responded to the treatment, the median progression-free survival has not been reached. In the non-responding patients, the median progression-free survival was 4 months. In patients with severe comorbid conditions and unwilling to accept conventional chemotherapy because of severe infection, the physical conditions improved significantly. ConclusionContinuous low-dose CP regimen is an effective and well-tolerated salvage therapy for MM. DisclosuresNo relevant conflicts of interest to declare.

Effect of dietary protein and lysine fluctuations in the absence and presence of ractopamine on performance and carcass quality of late-finishing pigs1

Two experiments with finishing pigs were conducted to evaluate the effects of fluctuating dietary CP levels and ractopamine on performance and carcass traits. In Exp. 1, a total of 408 finishing pigs (mixed sex) were assigned to 1 of 4 protein regimens. Average initial and final BW were 89 and 123 kg, respectively. Pigs on treatments 1 to 4 were fed 16, 11, 16, and 13% CP from wk 0 to 2, respectively. From wk 2 to 5, the pigs on regimens 1 to 4 were then fed 15, 18.33, 18, and 20% CP, respectively, with regimens 3 and 4 also containing supplemental ractopamine (9.9 mg/kg) from wk 2 to 5. Overall (wk 0 to 5), BW gain, G:F, loin depth, percentage of lean, and dressing percentage were improved (P < 0.05) in pigs on regimens 3 and 4 compared with those on regimens 1 and 2. No statistically significant overall (wk 0 to 5) protein sequence regimen differences occurred between the standard regimens (1 and 3) and the low-high CP regimens (2 and 4). Experiment 2 involved 172 finishing pigs (mixed sex) in 2 protein regimens. Average initial and final BW were 91 and 136 kg, respectively. The diets consisted of 1) a control (16% CP from d 0 to 14, 18% CP + 4.95 mg of ractopamine/kg from d 14 to 24, and 18% CP + 9.9 mg of ractopamine/kg from d 24 to 35; 2) a low-high CP regimen (12.5% CP from d 0 to 14, 20.33% CP + 4.95 mg of ractopamine/kg from d 14 to 24, and 20.33% CP + 9.9 mg of ractopamine/kg from d 24 to 35. From d 0 to 14, pigs fed the low CP diet (12.5% CP) had reduced (P < 0.05) BW gain and G:F compared with those fed the control diet (16% CP). In contrast, from d 14 to 35, pigs on the low-high regimen had improved (P < 0.08) BW gain and G:F compared with pigs on the control regimen. Despite the wide dietary CP fluctuations for pigs in Exp. 2, performance and carcass traits were similar for both regimens over the 35-d test period. These data indicate that pigs fed deficient levels of CP and Lys for 14 d, followed by increased levels of CP and Lys during a subsequent 21-d period can recover and achieve growth performance and carcass merit equal to that achieved with a conventional protein feeding regimen.

Response of coccidiostat- versus vaccination-protected broilers to gelatin inclusion in high and low crude protein diets

Experimentation examined if Gly and Ser (Gly + Ser) and Pro from gelatin inclusion in low and high CP feeds would relieve impaired performance of broilers after vaccination for coccidiosis. Broilers in floor pens were fed 20-18-16% or 23-20-18% CP corn-soybean meal regimens from 0 to 8 wk of age such that 1 or more of the most limiting essential amino acid levels were similar across treatments and considered adequate respective of age. Gelatin was included in diets at 2%, which contributed Gly + Ser and Pro levels comparable to using 5% meat meal. Half of the chicks were spray-vaccinated with live oocysts before placement and received nonmedicated feed, whereas the other half received coccidiostat-medicated (salinomycin) feed to 6 wk of age. Vaccination adversely affected live performance in the first 3 wk, which could not be fully compensated to the level of birds receiving coccidiostat by the end of experimentation. Inclusion of gelatin mitigated vaccination response through the first 3 wk, while improving overall live performance of birds fed low CP diets. Gelatin had no effect on carcass composition, but the low CP regimen increased abdominal fat and reduced carcass and breast meat relative to high CP feeds. Vaccination also reduced overall carcass weight; however, part yields were not affected. Males were generally more sensitive to treatments than females. The conditionally essential amino acids Gly + Ser and Pro may be important factors in recovery from live anticoccidial vaccines.

Net portal and hepatic flux of nutrients in growing wethers fed high-concentrate diets with oscillating protein concentrations1,2

We hypothesized that oscillating dietary CP would improve N retention by increasing the uptake of endogenous urea N by portal drained viscera (PDV), compared with static dietary CP regimens. Chronic indwelling catheters were surgically implanted in the abdominal aorta, a mesenteric vein, a hepatic vein, and the portal vein of 18 growing Dorset x Suffolk wethers (44.6 +/- 3.6 kg of BW). Wethers had ad libitum access to the following diets in a completely randomized block design: 1) Low (9.9% CP), 2) Medium (12.5% CP), or 3) Low and High (14.2% CP) diets oscillated on a 48-h interval (Osc). Dry matter intake was greater (P = 0.04) for the Osc diet (1,313 g/d) than the Low diet (987 g/d) and was intermediate for the Medium diet (1,112 g/d). Nitrogen intake was not different between the wethers fed the Osc (25.4 g/d) and Medium diets (22.2 g/d), but was lower (P < 0.01) in wethers fed the Low diet (16.0 g/d). Wethers fed the Osc diet (6.7 g/d) retained more (P < 0.04) N than did those fed the Medium diet (4.0 g/d). Hepatic arterial blood flow was not different (P = 0.81) between wethers fed the Osc (31 L/h) or Medium diet (39 L/h) but was greater (P = 0.05) in wethers fed the Low diet (66 L/h). Net release of alpha-amino N by the PDV did not differ (P = 0.90) between the Low (37.8 mmol/h) and Medium diets (41.5 mmol/h) or between the Osc (53.0 mmol/h) and Medium diets (P = 0.29). Net PDV release of ammonia N was less (P = 0.05) for the Low diet than for the Medium diet, and this was accompanied by a similar decrease (P = 0.04) in hepatic ammonia N uptake. Urea N concentrations tended to be (P = 0.06) less in arterial, portal, and hepatic blood in wethers fed the Low diet compared with those fed the Medium diet. Wethers fed the Osc diet tended (P = 0.06) to have a greater PDV uptake of urea N than did those fed the Medium diet, but there was no difference between the Osc and Medium diets (P = 0.72) in hepatic urea N release. Net PDV uptake of glutamine tended to be greater (P < 0.07) in wethers fed the Low diet (6.7 mmol/h) than those fed the Medium diet (2.7 mmol/h). These data indicate that oscillating dietary protein may improve N retention by increasing endogenous urea N uptake by the gastrointestinal tract.

N-acetylcysteine in the prevention of contrast agent-induced nephrotoxicity in patients undergoing computed tomography studies

We compared two chemotherapy regimens for advanced non small-cell lung cancer. The CG regimen consisted of carboplatin (AUC 4 to 5) on day 1 plus gemcitabine (1,000 mg/m(2)) on day 1 and 8, every three weeks, while the CP regimen was carboplatin (AUC 6) on day 1 plus paclitaxel (70 mg/m(2)) on day 1, 8 and 15, every four weeks. There was a total of 62 patients, 23 on the CG regimen and 39 on the CP regimen. In initial treatment, the response rate, time to progression and median survival time in the CG regimen and CP regimens were 40% vs 22%, 124 days vs 67 days, and 422 days vs 328 days, respectively. There was no statistical difference in the outcome. However, the toxicity profile was different in the two regimens. Grade 3/4 neutropenia and thrombocytopenia were frequent in the CG regimen (61% vs 31%, p=0.02, 44% vs 3%, p=0.0002, respectively). Non hematological toxicity including grade 2 alopecia was less in the CG regimen (4% vs 36%, p=0.012). In choosing the chemotherapeutic regimen for non small cell cancer, it is important to consider the toxicity.