Major Reason For Discontinuation Research Articles

Implementation of isoniazid preventive therapy among children living with diagnosed pulmonary tuberculosis patients: A mixed methods study from Mumbai, India.

Tuberculosis remains a significant public health issue, particularly among children who are in close contact with tuberculosis patients. India accounts for a large proportion of global tuberculosis cases. Despite global recommendations for Isoniazid Preventive Therapy to prevent latent tuberculosis infection from progressing to active disease, the initiation and adherence to Isoniazid Preventive Therapy remain suboptimal, especially in high-burden settings. Understanding the barriers to Isoniazid Preventive Therapy implementation is crucial to improving treatment outcomes and achieving tuberculosis elimination goals. This study aimed to quantify the uptake of isoniazid among children under 6 years who were started on Isoniazid Preventive Therapy and to identify the challenges from the perspectives of caregivers and healthcare providers. The study was conducted in a slum in Mumbai, India, from June to December 2023, using a mixed-methods design. The quantitative phase involved a house-to-house survey, covering all 96 contacts started on Isoniazid Preventive Therapy in 2022, using a semi-structured questionnaire. The qualitative phase included key informant interviews with healthcare providers and in-depth interviews with caregivers. Quantitative data were analysed using Fisher's exact test and chi-square test, while qualitative data were analysed thematically. Of the 96 children, 11 (11.45%) completed therapy, with an average treatment duration of 2.5 months. Quantitative findings highlighted fear of side effects and family migration as major reasons for discontinuation. Completion of chemoprophylaxis was significantly associated with factors like male gender, support from extended family, home visits by tuberculosis health staff, and shorter travel time (under 30 min) to the tuberculosis unit. Qualitative data revealed challenges across themes of supply, staff, training, services, and adherence. Key challenges included lack of awareness, unavailability of isoniazid in syrup form, inadequate training for health workers, weak program monitoring, insufficient staffing, and fears related to tuberculosis exposure during outpatient department visits. Effective counselling, regular follow-ups, availability of medications in syrup form, increasing staffing based on case burden, timely training of staff, strengthening program monitoring, and ensuring infection control in tuberculosis outpatient departments are critical to achieving successful completion of isoniazid preventive therapy.

Feasibility of S-1 adjuvant chemotherapy after major hepatectomy for biliary tract cancers: An exploratory subset analysis of JCOG1202

IntroductionMajor hepatectomy (MH) may produce the impaired liver function and affect the feasibility of adjuvant chemotherapy in terms of early period after the surgery, but there have not been detailed investigations. JCOG1202 (UMIN000011688) is a randomized phase III trial demonstrating the superiority of adjuvant S-1 chemotherapy for biliary tract cancer (BTC). The aim of this study is to examine the influence of MH for BTC on adjuvant S-1. Materials and methodsOf the total 424 patients, 207 received S-1 (S-1 arm) while the remaining 217 were not. We compared MH with non-major hepatectomy (NMH) for BTC. ResultsIn the S-1 arm, 42 had undergone MH, and 165 had undergone NMH. MH had similar pretreatment features to NMH, including the proportion of biliary reconstruction, to NMH, except for a lower platelet count (17.7 vs. 23.4 × 104/mm3, p < 0.0001) and lower serum albumin level (3.5 vs. 3.8 g/dL, p < 0.0001). The treatment completion proportion tended to be lower for MH than for NMH (59.5 % vs. 75.8 %; risk ratio, 0.786 [95 % confidence interval, 0.603–1.023], p = 0.0733), and the median dose intensity was lower as well (88.7 % vs. 99.6 %, p = 0.0358). The major reasons for discontinuation were biliary tract infections and gastrointestinal disorders after MH. The frequency of grade 3–4 biliary tract infection was 19.0 % in MH vs. 4.2 % in NMH. ConclusionThe treatment completion proportion and dose intensity were lower in MH than in NMH. Caution should be exercised against biliary tract infections and gastrointestinal disorders during adjuvant S-1 after MH for BTC.

Discontinuation Patterns Among Women Using Jadelle Contraceptive Devices in a Tertiary Hospital in South-South Nigeria

<i>Introduction</i>: The Jadelle subdermal contraceptive implant is a widely used hormonal contraceptive consisting of two rods, each consisting of a Levonorgestrel-releasing core encased in thin-walled silicon-rubber tubing. Our study examined the prevalence and discontinuation patterns of Jadelle among women in a Southern Nigerian Hospital. <i>Materials and Methods</i>: A review of the discontinuation patterns among Jadelle contraceptive device users in the University of Uyo Teaching Hospital over 3 years was carried out. The Case files of all clients who used Jadelle implant over the period were retrieved and analyzed. <i>Results</i>: Out of 2,980 clients using different contraceptive methods during the study period, 231 clients (7.8%) used the Jadelle implant. Of the 198 (85.7%) case notes available, most (52%) of them were aged 30-34 years, had attained a tertiary level of education (50.4%), and were grand-multiparous (50%). Fifty-six (56.6%) percent of clients used Jadelle for birth spacing while 44.5% used it for limiting family sizes. The most common menstrual pattern at 24 months follow-up was Amenorrhea (50%). Sixty clients (30.3%) discontinued the method for reasons which include the desire for pregnancy (48.3%), side effects (25%), change of method (11.5%), and husbands` view (5%). Discontinuation was more among the younger clients less than 36 years (86.7%). <i>Conclusion</i>: The Jadelle contraceptive device is associated with a number of side effects, however, the major reason for discontinuation was the desire for pregnancy, followed by the complications arising from Jadelle use. There is a need for more detailed client and spousal counseling, especially on the side effects of Jadelle to reduce discontinuation due to them.

Long-Term Efficacy, Safety, and Drug Survival of Guselkumab in Patients with Psoriasis: Real-World Data from the Czech Republic BIOREP Registry.

Real-world data on the long-term use of guselkumab for treatment of psoriasis are still limited. We aimed to evaluate long-term efficacy, safety, and drug survival of guselkumab in a real-world setting. This is a retrospective study analyzing Czech Republic registry (BIOREP) data of patients treated with guselkumab. In total, 333 patients were included. Improvement in Psoriasis Area and Severity Index (PASI) score was significant. Mean PASI score decreased from 16 at baseline to 0.7, 0.9, and 0.8 after 12, 24, and 36months, respectively. Absolute PASI scores of ≤ 3 and ≤ 1 were achieved in 93.9% and 77.9%, 94.2% and 71.0%, and 94.8% and 70.7% of patients after 12, 24, and 36months, respectively. Response PASI 90 and PASI 100 were attained in 81.8% and 57.1%, 75.4% and 50.7%, and 75.9% and 55.2% of patients after 12, 24, and 36months, respectively. The percentage of patients achieving PASI 90 and PASI 100 responses was higher throughout the study in bio-naive and in normal-weight patients, while presence of psoriatic arthritis had no influence. Improvement in Dermatology Life Quality Index (DLQI) score was also significant; mean DLQI score decreased from 14.2 at baseline to 0.9, 1.0, and 0.7 after 12, 24, and 36months, respectively. Patients with PASI 100 had lower mean DLQI throughout the study compared with patients with PASI 90. Major reason for discontinuation was loss of effectiveness in 7.1% of patients, while only 0.6% were due to adverse events. Overall cumulative drug survival was high, with only a minimal decline over time, reaching 91.6%, 87.0%, and 85.5% after 12, 24, and 36months, respectively. Drug survival was not affected by previous biological treatment, patient weight, or presence of psoriatic arthritis. This real-world study demonstrated the long-term effectiveness, good safety profile, and high drug survival of guselkumab treatment over a period of 36months.

Facilitators and barriers in acceptance of postpartum intrauterine contraceptive devices in Bihar

: In India, Postpartum IUCD services were introduced in 2010, which is being scaled up, in a phased manner. Insertion of PPIUCD during the immediate postpartum period provides increased motivation and focuses on the prevention of unintended pregnancies along with spacing. Spacing more than 2 years reduces one-third of maternal mortality and 10% of child mortality. This study is an attempt to understand facilitating factors and barriers to using PPIUCD in Bihar. : A cross-sectional study using a mix-method approach was conducted in nine divisional headquarters districts of Bihar – in various level health facilities. A total of 1620 women, 18-49 years who had institutional delivery and 344 Healthcare providers were covered. : Facilitating factors were awareness (53.2%), incentivization (50.5%), better quality of device/services along with incentivization, and proper training to ASHA/ANM (2.6%). The discontinuation rate of PPIUCD was 25.9% and the major reasons for discontinuation were health problems/side effects, husband/family member’s disapproval, and preference for another method. Major barriers for non-acceptance were the preference for another method, Husband/Family member’s disapproval, Health problems/side effects, and Lack of awareness.: Comprehensive counseling during ANC, Delivery and of husband/family members, publicity through mass media, educational campaigns, timely incentivization, regular follow-up check-ups, Promoting of PPIUCD by the healthcare providers are some of the ways to address the barriers and thereby facilitate the use of PPIUCD.

Efficacy, safety, and drug survival of patients with psoriasis treated with IL-17 inhibitors – brodalumab, ixekizumab, and secukinumab: real-world data from the Czech Republic BIOREP registry

Background Real-world data on the use of interleukin-17 (IL-17) inhibitors for the treatment of psoriasis are limited. Objective To evaluate and compare the efficacy, safety, and drug survival of IL-17 inhibitors. Methods This retrospective study analyzed the BIOREP registry data of patients treated with at least one IL-17 inhibitor (secukinumab, ixekizumab, and brodalumab). Results In total, 949 patients were included. The improvement in PASI score was significant for all drugs, and the proportion of patients achieving PASI 75, 90, and 100 after both 3 and 24 months of therapy was highest for brodalumab, followed by ixekizumab and secukinumab. The Dermatology Life Quality Index score decreased to ˂3 after 3 months and to ˂2 after 24 months of therapy for all inhibitors. Loss of effectiveness was the major reason for discontinuation in 17.2% of patients, followed by adverse events in 3.2% of patients. The drug survival probability was the highest for brodalumab, followed by ixekizumab and secukinumab. Negative predictors for treatment discontinuation were obesity and the number of treatment lines, whereas a positive predictor was the presence of concomitant psoriatic arthritis; sex had no influence. Conclusion This real-life study demonstrated the effectiveness and good safety profile of all currently available IL-17 inhibitors.

Assessing the Determinants and Clues-to-Actions Influencing the Uptake of Modern Contraceptives Among Women of Reproductive Age 15-49 years in Federal Capital Territory, Abuja, Nigeria

The contraceptive prevalence rate for any family planning method among currently married women in Federal Capital Territory (FCT) is 23.9%; use of any modern method (20.3%) among currently married women, use of any traditional method (3.6%), not currently using any method (76.1%), and total fertility rate is 4.3 per woman (NDHS 2018). The study aimed at assessing the determinants and clues-to-action influencing the uptake of contraceptives among women of childbearing age (15-49) years. A cross-sectional household survey was conducted from February 20-March 15, 2019 in FCT, Abuja. A multi-stage sampling method was used to recruit 360 women, out of which 348 were successfully interviewed by trained interviewers yielding a response rate of 96.7%. SPSS version 20.0 was used for analysis. Findings revealed that 94.4% of women were aware of family planning services, 24.4% reported of ever used any family planning methods, 20.6% used any modern method, and 3.8% using any traditional method. Major reasons for discontinuation of modern contraceptives indicated were: became pregnant while using contraceptives (33.8%), desire to become pregnant (31.8%), delay in conception (30.9%), health concerns (24.3%), fear of having disable babies (22.1%) and side effects (13.8%). Applying Health Beliefs model the clues-to-action for uptake of contraceptives were: quality-of-care, women’s satisfaction of products, beliefs/attitude, side effects and health concerns. Review demand creation strategies to include community health - and religious leaders as change agents, invest more in education. pharmaceutical companies to review products side effects, aggressive marketing, harmonization of stakeholders’ effort to reduce duplication, and entrench central database.

A multicenter retrospective study of nivolumab monotherapy in previously treated metastatic renal cell carcinoma patients: interim analysis of Japanese real-world data

BackgroundIn a phase III clinical trial, CheckMate 025, treatment of metastatic renal cell carcinoma (mRCC) with nivolumab demonstrated superior efficacy over everolimus. However, as the clinical trial excluded patients with specific complications and poor performance status (PS), the effectiveness and safety of nivolumab in clinical practice, in which patients with various clinical complications are treated, is unclear. This study explored real-world nivolumab treatment in Japanese mRCC patients.MethodsThis is an interim analysis of a multicenter, non-interventional, medical record review study (minimum follow-up: 9 months). All eligible Japanese mRCC patients who first received nivolumab between February and October 2017 were included; data cut-off was April 2019. We analyzed nivolumab treatment patterns, efficacy (including overall survival, progression-free survival, objective response rate, and duration of response) and safety (including immune-related adverse events).ResultsOf 208 evaluable patients, 31.7% received nivolumab as fourth- or later line of treatment. At data cut-off, 26.9% of patients were continuing nivolumab treatment. The major reason for discontinuation was disease progression (n = 100, 65.8%). Median overall survival was not reached; the 12-month survival rate was 75.6%. Median progression-free survival was 7.1 months, the objective response rate was 22.6%, and median duration of response was 13.3 months. Patients who were excluded or limited in number in CheckMate 025, such as those with non-clear cell RCC or poor PS, also received benefits from nivolumab treatment. Immune-related adverse events occurred in 27.4% of patients (grade ≥ 3, 10.1%).ConclusionNivolumab was effective and well-tolerated in real-world Japanese mRCC patients.Trial registrationUMIN000033312

Prevalence of Dog Bite among Field Workers at a Primary Health Care Level in Goa.

This study was undertaken in 121 field workers in a primary health care set up in Goa to estimate the lifetime and annual incidence dog bite, and to assess their knowledge and practices regarding post-exposure prophylaxis. The annual and lifetime incidence of dog bite was 3.3% and 22.3%, respectively. Based on the comparable figures from studies in general population, Dog-bite seems to be an occupational hazard among these workers. Only 28.9% completed the full course of anti-rabies vaccine with its cost as the major reason for discontinuation. More than 90% consulted traditional healers and wound toilet was done by 70%. The overall knowledge and practices seemed better than those reported in other studies, but continued orientation of the field workers and access to free vaccination at the workplace is of paramount importance.

The use of levonorgestrel releasing intrauterine system at Ahmadu Bello University Teaching Hospital, Zaria

Background: The intrauterine system (IUS) is an intrauterine device which releases levonorgestrel (LNG). It is used in preventing pregnancy for up to 5 years as well as to treat heavy menstrual bleeding. Data documenting the use of IUS is very limited in our setting. Objective: To review the use of the LNG IUS and the reasons for its use. Materials and Methods: In this study, we reviewed records of all clients who attended the reproductive health clinic of the Ahmadu Bello University Teaching Hospital, Zaria and selected an intrauterine device as a method of contraception and or therapeutic option. The study was conducted from January 2007 to December 2013. Data was analysed using the Statistical Package for the Social Sciences (SPSS) version 20. Results: A total of 1104 women opted for an IUD as a method for contraception, of which 68 (6.1%) women used LNG IUS. The mean age of the women was 31.9 years ± 6.8 years. Over half (54.5%) had between 2 and 4 children. There were only 6 (11.8%) women who used the IUS for reasons other than contraception during the study period, majority had the device inserted for contraception. Side-effect was the major reason for discontinuation (29.4%) followed by the desire to have a baby (27.9%). The most common side-effect was irregular vaginal bleeding (23.5%). Conclusion: The uptake of LNG IUS (Mirena®) for contraception or therapy is very low in our setting. There is a need to educate both the healthcare providers and clients regarding the contraceptive and non-contraceptive benefits of Merina.

EPS06.9 Real world introduction of Colobreathe™ in children and adults with cystic fibrosis

Objectives: To evaluate the introduction of ColobreatheTM (Colo) from June to November 2015 in French patients attending 2 paediatric and 2 adult CF centres. Methods: All patients were similarly educated on how to inhale Colo (explanations, video) and received a test dose at the CF centre. Telephone follow-up with a CF caregiver was set up at days 1, 3 and 14 in order to assess tolerance and advise patients. Reasons for treatment interruption during the first month were collected. Results: 123 patients (adults 71%, median age 24 years, mean FEV1 % pred. 64±25) received a test dose of Colo. 67% were previously treated by inhaled colistine and 20% had no inhaled antibiotics. Out of the 112 patients who completed the trial, 27.7% interrupted treatment within one month. The reasons were cough (n =22, 71%), bad taste (n = 3), technical problems (n =4), treatment burden (n =2), urticaria (n = 1), medical decision (n =1) or hemoptysis (n = 1). No difference could be seen between those who had and had not interrupted treatment at one month as to age or FEV1, but patients already treated by inhaled colistine were less likely to stop treatment. In the 81 patients who completed one month treatment, cough was also frequently reported but its incidence progressively decreased (50% at D1, 36% at D3, and 14% at D30). 13 out of 112 patients (12%) had technical problems, mainly blocking of the device or broken capsule. At one month, treatment burden was scored at 2 (on a 1–10 scale). Conclusion: Education at introduction of Colo resulted in continuation of treatment in 72% of the patients at one month, cough being the major reason for discontinuation of treatment. Long term assessment is needed. ePS06.10 Antibiotic desensitisation: a single centre review of 2015 M.K. Dooney, K.J. Cox, P.J. Barry, A.K. Webb, A.M. Jones, R.J. Bright-Thomas. Manchester Adult Cystic Fibrosis Centre, Manchester, United Kingdom

Abstract P3-07-40: Pharmacogenetic study of exemestane and everolimus in metastatic breast cancer patients progressing on prior non-steroidal aromatase inhibitors

Abstract Background: Activation of the mTOR pathway has been observed in patients (pts) with metastatic breast cancer (MBC) progressing on endocrine therapy. BOLERO-2 trial demonstrated a significant increase in progression free survival (PFS) obtained with everolimus (EVE) and exemestane (EXE) versus EXE alone in pts refractory to a prior non-steroidal aromatase inhibitors (NSAI). However, there is large interindividual variability in toxicity and efficacy profiles of EXE-EVE treatment. Single Nucleotide Polymorphisms (SNPs) have been proposed to explain some of these differences. The objective of this study was to perform a pharmacogenetic analysis to identify SNPs associated with EVE toxicity and activity. Methods: This is a prospective unicentric clinical trial for postmenopausal pts with hormone receptor-positive, HER2 negative, MBC progressing on prior NSAI, treated with EXE-EVE. Blood samples were obtained from all pts, and 12 SNPs in key genes involved in EXE pharmacokinetics (ABCB1, CYP2C8, CYP3A4, CYP3A5) and pharmacodynamics (AKT1, AKT2, FGFR4, PHLPP2, PIK3R1, RAPTOR) were genotyped. EVE pharmacokinetics data was available for a subset of 37 pts. The association between the SNPs and EVE pharmacokinetic parameters were analyzed using U-Mann-Whitney test. A selection of clinically relevant toxicities (non-infectious pneumonitis (NIP), mucositis, hyperglycemia and hematological) was analyzed using binary logistic regression. Cox regression was used to analyze the association of SNPs with time to treatment modifications (reduction or interruption) due to toxicity, PFS and OS. Results: 90 patients with median age of 62 yrs were included. At data cut off, a total of 77 pts had discontinued treatment. Major reasons for discontinuation were: disease progression (80%), adverse events (17%) and death (2%). Number of prior chemotherapy lines: 0; 50%, 1;18%, 2;10%, ≥3; 22%. 76% of pts experienced at least one adverse event related to EVE. CYP3A4 rs35599367 (CYP3A4*22 allele) heterozygous pts had higher EVE concentration in blood compared to wild type pts (P=0.019), in agreement with previous data. Regarding EVE toxicities, ABCB1 SNP rs1045642 showed a higher risk of mucositis (HR=2.3, 95%CI=1.1-4.8, P=0.031; multivariable analysis), and PIK3R1 rs10515074 variant was inversely associated with hyperglycemia (HR=0.24, 95%CI=0.1-0.8, P=0.016; multivariable analysis). RAPTOR rs9906827 protected for NIP (HR=0.38, 95%CI=0.2-0.9, P=0.024; multivariable analysis). When analyzing the time to treatment modification due to any toxicity, we observed a trend for FGFR4 rs351855 and RAPTOR rs9906827 (HR=0.59, 95%CI=0.3-1.0, P=0.06 and HR=0.71, 95%CI=0.5-1.1, P=0.12; respectively, in multivariable analysis). Regarding activity, RAPTOR rs9906827 was also associated with longer PFS (dominant model HR=0.48, 95%CI=0.3-0.8, P=0.006; multivariable analysis). No SNP was significantly associated with OS. Conclusions: We found altered EVE pharmacokinetics for CYP3A4*22 carriers and protection for NIP and longer PFS for RAPTOR rs9906827. This study supports prospective trials for genetic testing prior to EXE-EVE therapy to stratify patients according to toxicity and efficacy risk profiles. Citation Format: Pascual-Martínez T, Apellániz-Ruiz M, Pernaut C, Cueto-Felgueroso C, Villalba P, Alvarez C, Manso L, Rodriguez-Antona C, Ciruelos EM. Pharmacogenetic study of exemestane and everolimus in metastatic breast cancer patients progressing on prior non-steroidal aromatase inhibitors. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-40.

Prognostic value of flare-up phenomenon after discontinuation of sunitinib (SU) or pazopanib (PA) in metastatic renal cell carcinoma (mRCC).

448 Background: SU and PA are VEGFR inhibitors, approved for the treatment of mRCC. Cessation of treatment has been reported to induce flare-up, with increased tumor growth rate (TGR). We aimed to investigate this phenomenon and its prognostic role in mRCC. Methods: Patients who discontinued first line SU or PA with available data about CT scans performed before (t-1), at the time of discontinuation (t0) and after (t+1), were included in this analysis. TGR was evaluated as the difference between the sum of longest diameters (SLD) of the target lesions during the interval time between the CTs (TGR1=SLD0–SLD-1/t0-t-1 and TGR2=SLD+1-SLD0/t+1-t0) and expressed in cm/month. Flare-up was evaluated as the difference between the TGRs. Median overall survival was evaluated from t0 (OS0) to death by the Kaplan-Meier method and correlation with variables was evaluated with Cox model. Results: Sixty-three patients treated from Oct 2006 to Nov 2012 at the Institut Gustave Roussy were eligible. Median age was 57.1 y, 81% were males, 89% had SU and 11% PA. Heng prognostic groups were good in 33% and intermediate in 67% of the pts. Median OS0 was 24.1 months (95%CI, 8.3 – 40.0). Major reasons for discontinuation were durable partial/complete response (16%), severe toxicity (22%) and progression of disease (62%). The median TGR1 and TGR2 were 0.2 and 0.7 cm/month, respectively (p=0.001), no correlation was found (p=0.33) and no differences were found between SU and PA in TGR1 (p=0.95) and TGR2 (p=0.53). Median flare-up was 0.5 cm/month (IQR: 0.1 – 1.2); in pts who discontinued for response, toxicity, or PD it was 0.1 (IQR: -0.2 – 0.6), 0.5 (IQR; 0.2 – 2.0) and 0.8 (0.1 – 1.7), respectively. At the univariate analysis flare-up was a prognostic factor for OS0 (HR: 1.13, 95%CI: 1.02 – 1.24; p=0.018). When compared to Heng criteria in the multivariate analysis, it was confirmed to be an independent prognostic factor: each increase of 1 cm in flare-up increases the risk of death by 11% (HR: 1.11, 95%CI: 1.00 – 1.23; p=0.048). Conclusions: Flare-up is an independent prognostic factor present in patients affected by mRCC who discontinued SU or PA. This is independent by the reason for discontinuation and the type of therapy.

Abstract P1-14-02: Preoperative docetaxel (T) with or without capecitabine (X) following epirubicin, 5-fluorouracil and cyclophosphamide (FEC) in patients with operable breast cancer (OOTR N003): Results of comparative study and predictive marker analysis

Abstract Objective: This preoperative study aimed to evaluate the efficacy of 4 cycles of TX compared with 4 cycles of T, following 4 cycles of FEC in operable breast cancer patients. Methods: Women with operable breast cancer (T1C-3N0M0/T1-3N1M0) were randomly assigned to receive either T (75 mg/m2, q3) plus X (825 mg/m2 bid, days 1 to 14) or T alone (75 mg/m2, q3) after completion of FEC (5-fluorouracil 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2, q3). Patients who had disease progression on FEC were excluded from randomization. The primary endpoint was pathological complete response (pCR). Predictive factor analysis was conducted using clinicopathological markers such as hormone receptors, Ki67 labeling index (Ki67LI) and thymidine phosphorylase (TP). Results: From November 2005 to October 2009, 504 patients were enrolled and 239 and 238 patients were assigned to TX and T group, respectively (median age 49 years, median tumor size 3.5 cm and node positive rate 56%). Treatment discontinuation was observed in 22% of TX group and 5% in T group (p &amp;lt; 0.0001). The major reasons for discontinuation were toxicity, refusal/ consent withdrawal and several others. No significant difference in pCR rate was shown between the two groups (TX 23% and T 24%, p = 0.748). Neither clinical response nor surgical outcome differed between TX and T. The pCR rate in patients who had therapy discontinuation or dose-reduction on TX was 23%, whereas pCR rate in those on T was 11%. A subpopulation treatment effect pattern plots method indicated a trend that TX may improve the pCR rate in patients having a middle range of pretreatment Ki67LI, such as 10%–20%. In the median follow-up time of 3.7 years, disease-free survival (DFS) was not different between TX and T (3-year DFS: 92% in TX and 91% in T; hazard ratio 0.907, 95%CI 0.528–1.557, p = 0.723). The frequency of major grade 3 or greater adverse events of TX and T were leukopenia, 36% and 34%, febrile neutropenia 8% and 5%, and hand-foot syndrome 15% and 2%, respectively. According to the analysis for evaluating predictive values of biomarkers, a multivariate logistic regression analysis showed that HER2 (+/−: odds ratio 4.107, p &amp;lt; 0.0001), Ki67LI (continuous variables: 1.029, p = 0.003), hormone receptor status (+/−: 0.457, p = 0.009), stroma TP status (0.523, p = 0.02) and grade (1/3: 0.387, 2/3: 0.532, p = 0.047) had statistical significant values for predicting pCR. A multiple Cox model in landmark analysis showed that tumor size (p &amp;lt; 0.0001), cancer cell TP status (p = 0.005), pCR and posttreatment Ki67LI (p = 0.016), and age (p = 0.049) were associated with DFS significantly. Conclusions: Addition of X to T showed no superiority to T alone following FEC in neoadjuvant treatment of these patients with operable breast cancer. Treatment discontinuation rate was significantly higher in TX than T group, however the pCR rate in patients in TX group who required treatment discontinuation or dose-reduction was similar to that in patients who completed as scheduled, which was different from T group. Determination of pre-/ post-treatment Ki67LI looks useful for predicting pCR and DFS. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-02.

Factors Affecting IUCD Discontinuation in Nepal

Information related to contraception discontinuation, especially in the context of Nepal is very limited. A nested case-control study was carried out to determine the factors affecting discontinuation of intrauterine contraceptive devices (IUCDs). A total of 115 cases (IUCD discontinuers) and 115 controls (IUCD continuers) were randomly selected based on the data obtained from the user's record of a family planning center in Kathmandu. Matching criteria were age during insertion and date of insertion of IUCD. Logistic regression was used to analyze the data. When cases were compared with controls, the results showed that place of residence, sex of last child, reproductive intention, experience of side effects, and follow-up practice were associated with discontinuation of the IUCD. Experience of side effects has been seen as the major reason for discontinuation. The results suggest that side effects after IUCD insertion should be properly discussed and promptly treated to reduce the discontinuation rate.

Menopausal-type symptoms among breast cancer patients on aromatase inhibitor therapy

ABSTRACTObjectives To examine self-reported menopausal-type symptoms among breast cancer patients on aromatase inhibitors (AIs) compared to women of the same age who had not been diagnosed with cancer, and to determine whether the percentage of breast cancer patients experiencing these symptoms changed over the first 6 months of AI treatment.Methods Data from a 6-month cohort study of 100 breast cancer patients initiating AI therapy and of 200 women of a similar age without a history of cancer were analyzed. At baseline (prior to the initiation of AI therapy among the breast cancer patients), 3 months, and 6 months, a comprehensive questionnaire was administered to participants that ascertained data on the experiencing of specific menopausal-type symptoms.Results The data showed statistically significant increases in the prevalence of certain symptoms from baseline to either follow-up point among the breast cancer patients; these symptoms included hot flushes, night sweats, pain during intercourse, hair loss, forgetfulness, depression, difficulty falling asleep, and interrupted sleep. Additionally, breast cancer patients were more likely than the women in the comparison group to report the new onset of many of these same symptoms during the follow-up time period.Conclusions Because bothersome symptoms and side-effects are a major reason for discontinuation and non-adherence to treatment, symptoms should be monitored and addressed by oncologists so that the breast cancer patient can maintain her quality of life and remain adherent to the treatment schedule.

High non-compliance in the use of letrozole after 2.5 years of extended adjuvant endocrine therapy. Results from the IDEAL randomized trial

AimsThe aim of this study was to investigate non-compliance to aromatase inhibitors and factors associated with early treatment discontinuation in the extended adjuvant setting. MethodsThe IDEAL trial is a prospective, open-label phase-III trial comparing 2.5 with 5 years of extended adjuvant letrozole (LET) in hormone receptor positive (HR+) postmenopausal early breast-cancer patients after 5 years of adjuvant endocrine therapy (ET). The purpose of this study was to assess non-compliance in the first 2.5 years of extended adjuvant therapy. Non-compliance was defined as early discontinuation of LET for all reasons, excluding death or recurrence. ResultsAt 2.5 years, 1215 patients were included in the analysis. Overall non-compliance probability was 18.4%, of which 85.1% discontinued due to toxicities. Analyses showed that patients with prior sequential therapy were less likely to discontinue treatment than when treated with AI or TAM upfront (logrank p = 0.004). Longer treatment-free intervals also predicted more non-compliance (logrank p = 0.011). Age was not predictive of non-compliance (p = 0.571). Prior surgery (mastectomy vs breast conserving surgery), both with or without radiotherapy and/or chemotherapy were also not associated with early treatment discontinuation (p = 0.228 and p = 0.585 respectively). Although having fewer than four positive lymph nodes predicted more non-compliance (logrank p = 0.050), age, tumor type and locoregional treatment did not. ConclusionsHigh non-compliance to extended ET was confirmed. Toxicities were the major reason for discontinuation, and this was not influenced by age. Longer treatment-free intervals and fewer positive lymph nodes predicted more non-compliance. Patients who underwent sequential therapy were least likely to discontinue extended adjuvant ET.

Treatment patterns in patients with HER2-positive early-stage breast cancer (ESBC) receiving adjuvant treatment with a trastuzumab-containing regimen.

624 Background: Patients with HER2-positive (HER2+) ESBC generally receive trastuzumab (H) containing chemotherapy adjuvant regimens, either anthracycline (A) containing (AC-TH or similar) or non-anthracycline containing (TCH or similar). This study evaluated patient characteristics and treatment patterns of patients with HER2 + ESBC who receive a H-containing regimen in a community setting. Methods: We conducted a retrospective study utilizing US Oncology’s iKnowMed EMR system. Female patients with HER2+ ESBC initiating adjuvant ACTH, TCH, ACTH-like or TCH-like regimens from 1-1-2006 to 6-30-2009 were identified. Patients in clinical trials or receiving concurrent treatment for other primary cancers were excluded. Patients were followed through 9-30-2010 to observe the duration of adjuvant treatment and reason for regimen discontinuation. Pearson chi square test for frequencies and logistic regression analyses were used for between group comparisons and to determine variables that predicted receipt of anthracycline based regimens. Results: We identified 1,029 patients with HER2+ ESBC who initiated an adjuvant regimen containing H between 1-1-2006 to 6-30-2009. Of these, 225 patients initiated ACTH, 158 patients initiated an ACTH-like regimen, 470 initiated TCH and 176 patients initiated a TCH-like regimen. Younger patients (OR: 2.33) and patients with higher stage at diagnosis (OR: 2.37) are significantly more likely (p<0.001) to receive an A based regimen. The treatment duration in the H product label is 448 days for ACTH and 365 days for TCH. The median (mean) treatment duration observed in this study was 392 (371) days for ACTH, 364 (305.1) days for ACTH like, 364 (299) days for TCH and 371 (329.7) for TCH like patients. The major reason for discontinuation was completion of treatment; toxicity was reported as a reason for discontinuation in 7.2% for ACTH and 1% for TCH. Conclusions: Younger patients with more aggressive disease were more likely to receive ACTH or ACTH like regimens of chemotherapy. The median duration of treatment was closer to the duration in product label for the TCH group versus ACTH with more patients on ACTH stopping treatment due to toxicity.

PMS64 PATIENT EXPERIENCE WITH SUBCUTANEOUS ANTI-TNF THERAPY AMONG RHEUMATOID ARTHRITIS PATIENTS

To describe the experience of RA patients with subcutaneous (SC) anti-TNF therapy from the patient perspective. Patients aged ≥18 and self-reporting an RA diagnosis completed a cross-sectional, self-administered, Internet-based questionnaire in August 2009. Biologic therapies included in the questionnaire were abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab and rituximab. This analysis focused on patients who reported current or past use of adalimumab (ADA) or etanercept (ETA), the most commonly prescribed SC anti-TNF agents. Certolizumab and golimumab were not included in the analyses due to the limited time they were available at the time of the study and their very small sample sizes. Patients provided information about their experiences with self-injection and how these experiences have affected self-reported discontinuation of therapy. A total of 263 patients were using SC anti-TNF therapy (129 ADA and 134 ETA) at the time of the survey. More than half of SC anti-TNF users (57%) experienced burning during or after injection. Of these, 15% rated the burning as very or extremely intense and 56% rated the burning as somewhat intense. Among SC users who reported that they did not take their medication as directed all the time (n=41), 12% cited discomfort in administering medication as often or very often a reason for treatment discontinuation. Of a small group of patients reported discontinuing in the year preceding the study (n=62), lack of efficacy, side effects, cost of drugs, and discomfort in administering medication were cited as major reasons for discontinuation. More than half of SC anti-TNF users experience burning during or after injection, and this discomfort may adversely affect treatment discontinuation. The results suggest that the patient experience should be considered when making treatment decisions. Further research is needed to examine the relationship between injection site reaction and patient outcomes including observed medication discontinuation.

Phase I study of pemetrexed (P) and pegylated liposomal doxorubicin (PLD) in patients with refractory breast, ovarian, primary peritoneal, or fallopian tube cancer

e13515 Background: P and PLD are clinically active as single agents and synergistic in preclinical models. This phase I, open-label trial determined the maximum tolerated dose (MTD) and safety profile of P followed by PLD in patients (pts) with breast or gynecologic cancers. Methods: Using standard phase I (3+3 dose escalation) study design, cohorts of 3–9 pts received escalating doses of P followed by PLD in 28-day cycles: P 400–500 mg/m2 on Days 1 and 15 and PLD 30–45 mg/m2 on Day 1. All pts received folic acid (350–1000 μg daily) and vitamin B12 (1000 μg) until 21 days after last dose of P. Pts continued until dose-limiting toxicity (DLT) or disease progression (PD) occurred. Results: From 11/05 to 1/08, 29 pts were registered/treated. Median age: 60.6 years (range, 47.5–80.1); ECOG performance status 0/1: 28%/72%; primary disease sites: ovarian (55%), breast (35%), peritoneal (10%); prior therapies: chemotherapy (100%), surgery (72%), hormones/biologics (35%), radiation (21%). Dosing results are shown below. At dose level (L) 2 and L3, 1 pt/cohort had DLTs; L5 was added and 3/3 pts had DLTs; 4 more pts were treated at L4 (1 pt replaced). Most frequent drug-related Grade 3–4 hematologic toxicities: neutropenia (86%), leukopenia (59%), thrombocytopenia (48%), anemia (41%). Most frequent drug-related Grade 3–4 nonhematologic toxicities: hand-foot syndrome (14%), hypokalaemia (10%). Major reasons for discontinuation: PD (48%), toxicity (28%), pt request (14%). Overall best responses (n=24): 5 pts (21%) had partial response (PR), 14 pts (58%) had stable disease (SD), 2 pts (8%) had PD, 3 pts (13%) were not evaluable. All 5 PR and 8 SD pts were ovarian; 5 SD and both PD pts were breast. Conclusions: P followed by PLD was reasonably tolerated in this heavily-pretreated population. The MTD was P 500 mg/m2 and PLD 40 mg/m2. These dose levels may be carried forward to phase II studies in more specific patient populations. [Table: see text] [Table: see text]